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Forensic Toxicology

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Open Access 01-01-2021 | Review Article

Counterfeit formulations: analytical perspective on anorectics

Authors: Dan Osei Mensah Bonsu, Constance Afoakwah, Maria de la Paz Aguilar-Caballos

Published in: Forensic Toxicology | Issue 1/2021

Abstract

Purpose

This paper examines the scope of anorectics in counterfeit weight-reducing formulations and provides insight into the present state of research in determining such adulterants. Analytical techniques utilised in profiling adulterants found in slimming products, including limitations and mitigation steps of these conventional methods are also discussed. The current legal status of the anorectics and analogues routinely encountered in non-prescription slimming formulations is also explored.

Methods

All reviewed literature was extracted from Scopus, Web of Science, PubMed, and Google Scholar databases using relevant search terms, such as, ‘counterfeit drugs’, ‘weight loss drugs’, ‘weight-reducing drugs’, ‘slimming drugs’, ‘anorectic agents’, and ‘counterfeit anorexics’. Legislation related to anorectics was obtained from the portals of various government and international agencies.

Results

Anorectics frequently profiled in counterfeit slimming formulations are mostly amphetamine derivatives or its analogues. Five routinely reported pharmacological classes of adulterants, namely anxiolytics, diuretics, antidepressants, laxatives, and stimulants, are mainly utilised as coadjuvants in fake weigh-reducing formulations to increase bioavailability or to minimise anticipated side effects. Liquid and gas chromatography coupled with mass spectrometric detectors are predominantly used techniques for anorectic analysis due to the possibility of obtaining detailed information of adulterants. However, interference from the complex sample matrices of these fake products limits the accuracy of these methods and requires robust sample preparation methods for enhanced sensitivity and selectivity. The most common anorectics found in counterfeit slimming medicines are either completely banned or available by prescription only, in many countries.

Conclusions

Slimming formulations doped with anorectic cocktails to boost their weight-reducing efficacy are not uncommon. Liquid chromatography combined with mass spectrometry remains the gold standard for counterfeit drug analysis, and requires improved preconcentration methods for rapid and quantitative identification of specific chemical constituents. Extensive method development and validation, targeted at refining existing techniques while developing new ones, is expected to improve the analytical profiling of counterfeit anorectics significantly.

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Cabezas M-D (2010) Counterfeit medicines as global treat. Pharm Policy Law 12:179–192. https://doi.org/10.3233/PPL-2010-0304CrossRef

Jackson G, Patel S, Khan S (2012) Assessing the problem of counterfeit medications in the United Kingdom. Int J Clin Pract 66:241–250. https://doi.org/10.1111/j.1742-1241.2011.02826.xCrossRefPubMed

Deisingh A-K (2005) Pharmaceutical counterfeiting. Analyst 130:271–279. https://doi.org/10.1039/b407759hCrossRefPubMed

Europharm Forum (2009) Framework for a guide on counterfeit medicines for pharmacists. shorturl.at/divFN. Accessed 15 Jul 2020

Pharmaceutical Security Institute (PSI) (2019) Pharma crime: geographic distribution. https://www.psi-inc.org/geographic-distribution. Accessed 1 Jun 2020

Dégardin K, Roggo Y, Margot P (2015) Forensic intelligence for medicine anti-counterfeiting. Forensic Sci Int 248:15–32. https://doi.org/10.1016/j.forsciint.2014.11.015CrossRefPubMed

Medicines and Healthcare products Regulatory Agency (2018) UK seizes more than £2 million of fake medicines as part of international crackdown. https://www.gov.uk/government/news/uk-seizes-more-than-2-million-of-fake-medicines-as-part-of-international-crackdown. Accessed 1 Jun 2020

Interpol (2019) Operation Pangea—shining a light on pharmaceutical crime. https://www.interpol.int/en/News-and-Events/News/2019/Operation-Pangea-shining-a-light-on-pharmaceutical-crime. Accessed 1 Jun 2020

UNODC (2019) What we have learned over the last ten years: a summary of knowledge acquired and produced by the UN system on drug-related matters. https://www.unodc.org/documents/commissions/CND/2019/Contributions/UN_Entities/What_we_have_learned_over_the_last_ten_years_-_14_March_2019_-_w_signature.pdf. Accessed 1 Jun 2020

10.

Acri K (2018) They cost us billions and they can kill: counterfeit drugs are invading Canada. In: Financ. Post. https://business.financialpost.com/opinion/they-cost-us-billions-and-they-can-kill-counterfeit-drugs-are-invading-canada. Accessed 1 Jun 2020

11.

Acri KML, Lybecker N (2018) Pharmaceutical counterfeiting: endangering public health, society and the economy. In: Fraser Inst. https://www.fraserinstitute.org/sites/default/files/pharmaceutical-counterfeiting-endangering-public-health-society-and-the-economy.pdf. Accessed 1 Jun 2020

12.

Swissmedic (2013) Over 400kg of fake anxiolytic seized at Zurich airport. React Wkly 1475:3. https://doi.org/10.1007/s40278-013-6698-2CrossRef

13.

Kelesidis T, Kelesidis I, Rafailidis PI, Falagas ME (2007) Counterfeit or substandard antimicrobial drugs: a review of the scientific evidence. J Antimicrob Chemother 60:214–236. https://doi.org/10.1093/jac/dkm109CrossRefPubMed

14.

Gaudiano M-C, Di Maggio A, Antoniella E, Valvo L, Bertocchi P, Manna L, Bartolomei M, Alimonti S, Rodomonte A-L (2008) An LC method for the simultaneous screening of some common counterfeit and sub-standard antibiotics: validation and uncertainty estimation. J Pharm Biomed Anal 48:303–309. https://doi.org/10.1016/j.jpba.2007.12.032CrossRefPubMed

15.

Delepierre A, Gayot A, Carpentier A (2012) Update on counterfeit antibiotics worldwide; public health risks. Med Mal Infect 42:247–255. https://doi.org/10.1016/j.medmal.2012.04.007CrossRefPubMed

16.

Newton PN, Amin AA, Bird C, Passmore P, Dukes G, Tomson G, Simons B, Bate R, Guerin PJ, White NJ (2011) The primacy of public health considerations in defining poor quality medicines. PLoS Med 8:e1001139. https://doi.org/10.1371/journal.pmed.1001139CrossRefPubMedPubMedCentral

17.

Newton PN, White NJ, Rozandaal JA, Green MD (2002) Murder by fake drugs: time for international action. BMJ 324:800–801. https://doi.org/10.1136/bmj.324.7341.800CrossRefPubMedPubMedCentral

18.

Sacré P-Y, Deconinck E, Chiap P, Crommen J, Mansion F, Rozet E, Courselle P, De Beer J-O (2011) Development and validation of a ultra-high-performance liquid chromatography-UV method for the detection and quantification of erectile dysfunction drugs and some of their analogues found in counterfeit medicines. J Chromatogr A 1218:6439–6447. https://doi.org/10.1016/j.chroma.2011.07.029CrossRefPubMed

19.

Tero-Vescan A, Vari C-E, Filip C, Ősz B-E, Ceană D, Imre S, Hancu G (2014) Analysis of dietary supplements and drugs forerectile dysfunction by HPLC-UV. Acta Medica Transilvanica 2:297–299

20.

de Carvalho LM, Correia D, Garcia SC, de Bairros AV, do Nascimento PC, Bohrer D (2010) A new method for the simultaneous determination of 1,4-benzodiazepines and amfepramone as adulterants in phytotherapeutic formulations by voltammetry. Forensic Sci Int 202:75–81. https://doi.org/10.1016/j.forsciint.2010.04.030CrossRefPubMed

21.

Parodi B, Caviglioli G, Bachi A, Cafaggi S, Romussi G (1993) Herbal mixtures with claimed slimming activity: determination by TLC and HPLC of illegally added drugs. Pharmazie 48:678–681 (PMID:8234401)PubMed

22.

Tang MHY, Chen SPL, Ng SW, Chan AYW, Mak TWL (2011) Case series on a diversity of illicit weight-reducing agents: from the well known to the unexpected. Br J Clin Pharmacol 71:250–253. https://doi.org/10.1111/j.1365-2125.2010.03822.xCrossRefPubMedPubMedCentral

23.

Dégardin K, Roggo Y, Margot P (2014) Understanding and fighting the medicine counterfeit market. J Pharm Biomed Anal 87:167–175. https://doi.org/10.1016/j.jpba.2013.01.009CrossRefPubMed

24.

Ariburnu E, Uludag MF, Yalcinkaya H, Yesilada E (2012) Comparative determination of sibutramine as an adulterant in natural slimming products by HPLC and HPTLC densitometry. J Pharm Biomed Anal 64–65:77–81. https://doi.org/10.1016/j.jpba.2012.02.004CrossRefPubMed

25.

de Carvalho LM, Martini M, Moreira APL, de Lima APS, Correia D, Falcão T, Garcia SC, de Bairros AV, do Nascimento PC, Bohrer D, (2011) Presence of synthetic pharmaceuticals as adulterants in slimming phytotherapeutic formulations and their analytical determination. Forensic Sci Int 204:6–12. https://doi.org/10.1016/j.forsciint.2010.04.045CrossRefPubMed

26.

Kim JW, Kweon SJ, Park SK, Kim JY, Lee JH, Han KM, Cho S, Kim J, Han SY, Kim HJ, Kim WS (2013) Isolation and identification of a sibutramine analogue adulterated in slimming dietary supplements. Food Addit Contam Part A 30:1221–1229. https://doi.org/10.1080/19440049.2013.793826CrossRef

27.

Lee JH, Kim NS, Han KM, Kim SH, Cho S, Kim WS (2013) Monitoring by LC-MS/MS of 48 compounds of sildenafil, tadalafil, vardenafil and their analogues in illicit health food products in the Korean market advertised as enhancing male sexual performance. Food Addit Contam Part A 30:1849–1857. https://doi.org/10.1080/19440049.2013.826878CrossRef

28.

Um SY, Kim KB, Kim SH, Ju YC, Lee HS, Oh HY, Choi KH, Chung MW (2008) Determination of the active metabolites of sibutramine in rat serum using column-switching HPLC. J Sep Sci 31:2820–2826. https://doi.org/10.1002/jssc.200800041CrossRefPubMed

29.

Yuen YP, Lai CK, Poon WT, Ng SW, Chan AYW, Mak TWL (2007) Adulteration of over-the-counter slimming products with pharmaceutical analogue—an emerging threat. Hong Kong Med J 13:216–220 (open access article)PubMed

30.

Al-Safi SA, Ayoub NM, Ayoub AM, Al-Momany E, Al-Doghim I, Al-Balas M, Alkofahi AS, Aboul-Enein FH, Aboul-Enein BH (2008) Public awareness of the abuse of herbs and drugs to decrease body weight: a novel national survey in Jordan. J Public Health 16:205–213. https://doi.org/10.1007/s10389-007-0166-5CrossRef

31.

Kesting JR, Huang J, Sørensen D (2010) Identification of adulterants in a Chinese herbal medicine by LC-HRMS and LC-MS-SPE/NMR and comparative in vivo study with standards in a hypertensive rat model. J Pharm Biomed Anal 51:705–711. https://doi.org/10.1016/j.jpba.2009.09.043CrossRefPubMed

32.

Khazan M, Hedayati M, Kobarfard F, Askari S, Azizi F (2014) Identification and determination of synthetic pharmaceuticals as adulterants in eight common herbal weight loss supplements. Iran Red Crescent Med J 16:e15344. https://doi.org/10.5812/ircmj.15344CrossRefPubMedPubMedCentral

33.

Sombra LL, Gómez MR, Olsina R, Martínez LD, Silva MF (2005) Comparative study between capillary electrophoresis and high performance liquid chromatography in ‘guarana’ based phytopharmaceuticals. J Pharm Biomed Anal 36:989–994. https://doi.org/10.1016/j.jpba.2004.08.026CrossRefPubMed

34.

Wang J, Chen B, Yao S (2008) Analysis of six synthetic adulterants in herbal weight-reducing dietary supplements by LC electrospray ionization-MS. Food Addit Contam Part A 25:822–830. https://doi.org/10.1080/02652030801946553CrossRef

35.

Yano HM, Farias FF, Del Bianco MB, Trujillo LM (2013) Determination of the sibutramine content of dietary supplements using LC-ESI-MS/MS. Lat Am J Pharm 32:1164–1169 (open access article)

36.

Hobold E, de Arruda M (2015) Prevalence of overweight and obesity in schoolchildren: relationship with socioeconomic status, gender and age. Rev Bras Cineantropom e Desempenho Hum 17:156–164. https://doi.org/10.5007/1980-0037.2015v17n2p156CrossRef

37.

Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378:804–814. https://doi.org/10.1016/S0140-6736(11)60813-1CrossRefPubMed

38.

Bray GA (2013) Why do we need drugs to treat the patient with obesity? Obesity 21:893–899. https://doi.org/10.1002/oby.20394CrossRefPubMed

39.

Almuzaini T, Choonara I, Sammons H (2012) A systematic review of counterfeit and substandard medicines. Arch Dis Child 97(Suppl 1):A1–A2. https://doi.org/10.1136/archdischild-2012-301885.3CrossRef

40.

Fincham JE (2014) Counterfeit medications and their negative impacts on health care. Am J Pharm Educ 78:48. https://doi.org/10.5688/ajpe78348CrossRefPubMedPubMedCentral

41.

Filippatos TD, Kiortsis DN, Liberopoulos EN, Mikhailidis DP, Elisaf MS (2005) A review of the metabolic effects of sibutramine. Curr Med Res Opin 21:457–468. https://doi.org/10.1185/030079905X38132CrossRefPubMed

42.

Sánchez-Reyes L, Fanghänel G, Yamamoto J, Martínez-Rivas NL, Campos-Franco E, Berber A (2004) Use of sibutramine in overweight adult hispanic patients with type 2 diabetes mellitus: a 12-month, randomized, double-blind, placebo-controlled clinical trial. Clin Ther 26:1427–1435. https://doi.org/10.1016/j.clinthera.2004.09.017CrossRefPubMed

43.

Finer N (2002) Sibutramine: its mode of action and efficacy. Int J Obes 26:S29–S33. https://doi.org/10.1038/sj.ijo.0802216CrossRef

44.

Sharma B, Henderson DC (2008) Sibutramine: current status as an anti-obesity drug and its future perspectives. Expert Opin Pharmacother 9:2161–2173. https://doi.org/10.1517/14656566.9.12.2161CrossRefPubMed

45.

Astrup A (2000) Thermogenic drugs as a strategy for treatment of obesity. Endocrine 13:207–212. https://doi.org/10.1385/ENDO:13:2:207CrossRefPubMed

46.

Luque CA, Rey JA (2002) The discovery and status of sibutramine as an anti-obesity drug. Eur J Pharmacol 440:119–128. https://doi.org/10.1016/S0014-2999(02)01423-1CrossRefPubMed

47.

Mancini MC, Halpern A (2006) Pharmacological treatment of obesity. Arq Bras Endocrinol Metab 50:377–389. https://doi.org/10.1590/S0004-27302006000200024CrossRef

48.

Seagle HM, Bessesen DH, Hill JO (1998) Effects of sibutramine on resting metabolic rate and weight loss in overweight women. Obes Res 6:115–121. https://doi.org/10.1002/j.1550-8528.1998.tb00324.xCrossRefPubMed

49.

Walsh KM, Leen E, Lean MEJ (1999) The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females. Int J Obes 23:1009–1015. https://doi.org/10.1038/sj.ijo.0801045CrossRef

50.

Chang K, Mak TWL, Kwong L, So KT (2005) Valvular heart disease caused by Chinese proprietary slimming medicine adulterated with fenfluramine. Hong Kong J Paediatr (New Series) 10:55–58. http://www.hkjpaed.org/pdf/2005;10;55-58.pdf (open access article)

51.

Surapaneni P, Vinales KL, Najib MQ, Chaliki HP (2011) Valvular heart disease with the use of fenfluramine-phentermine. Texas Hear Inst J 38:581–583 (PMID:2216314)

52.

Chen SPL, Tang MHY, Ng SW, Poon WT, Chan AYW, Mak TWL (2010) Psychosis associated with usage of herbal slimming products adulterated with sibutramine: a case series. Clin Toxicol 48:832–838. https://doi.org/10.3109/15563650.2010.517208CrossRef

53.

Rojas LBA, Gomes MB (2013) Metformin: an old but still the best treatment for type 2 diabetes. Diabetol Metab Syndr 5:6. https://doi.org/10.1186/1758-5996-5-6CrossRefPubMedPubMedCentral

54.

Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE (2012) Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics 22:820–827. https://doi.org/10.1097/FPC.0b013e3283559b22CrossRefPubMedPubMedCentral

55.

Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM (2011) Clinical pharmacokinetics of metformin. Clin Pharmacokinet 50:81–98. https://doi.org/10.2165/11534750-000000000-00000CrossRefPubMed

56.

Scheen AJ (1996) Clinical pharmacokinetics of metformin. Clin Pharmacokinet 30:359–371. https://doi.org/10.2165/00003088-199630050-00003CrossRefPubMed

57.

Zhu Q, Cao Y, Cao Y, Chai Y, Lu F (2014) Rapid on-site TLC-SERS detection of four antidiabetes drugs used as adulterants in botanical dietary supplements. Anal Bioanal Chem 406:1877–1884. https://doi.org/10.1007/s00216-013-7605-7CrossRefPubMed

58.

FDA (2002) Metformin hydrochloride tablets. U.S. Food Drug Adm. http://www.fda.gov/ohrms/dockets/dailys/02/May02/053102/800471e6.pdf. Accessed 8 Jul 2015

59.

van Ieperen I, Vermeij CG, van Belo-van de Laar IRF, Doorenbos CJ (2015) Hemodialysis versus continuous venovenous hemofiltration treatment of metformin associated lactic acidosis. Nephrol Dial Transplant 30(Suppl. 3):241. https://doi.org/10.1093/ndt/gfv179.37CrossRef

60.

Weisberg LS (2015) Lactic acidosis in apatient with type 2 diabetes mellitus. Clin J Am Soc Nephrol 10:1476–1483. https://doi.org/10.2215/CJN.10871014CrossRefPubMedPubMedCentral

61.

Wolf C, Tanner M (2002) Obesity. West J Med 176:23–28. https://doi.org/10.1136/ewjm.176.1.23CrossRefPubMedPubMedCentral

62.

Uwaifo GI, Melcescu E, McDonald A, Koch CA (2009) A case of profound weight loss secondary to use of phentermine. J Miss State Med Assoc 50:407–415 (PMID:20806811)PubMed

63.

Cosentino G, Conrad AD, Uwaifo GI (2013) Phentermine and topiramate for the management of obesity: a review. Drug Des Devel Ther 7:267–278. https://doi.org/10.2147/DDDT.S31443CrossRefPubMed

64.

Moldovan CP, Weldon AJ, Daher NS, Schneider LE, Bellinger DL, Berk LS, Hermé AC, Aréchiga AL, Davis WL, Peters WR (2016) Effects of a meal replacement system alone or in combination with phentermine on weight loss and food cravings. Obesity 24:2344–2350. https://doi.org/10.1002/oby.21649CrossRefPubMed

65.

Yanovski SZ, Yanovski JA (2014) Long-term drug treatment for obesity. JAMA 311:74–86. https://doi.org/10.1001/jama.2013.281361CrossRefPubMedPubMedCentral

66.

Bain JA, Dority JS, Cook AM (2014) Subarachnoid hemorrhage in a patient taking phentermine for weight loss. J Am Pharm Assoc 54:548–551. https://doi.org/10.1331/JAPhA.2014.13226CrossRef

67.

Hendricks EJ, Greenway FL (2011) A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther 18:292–299. https://doi.org/10.1097/MJT.0b013e3181d070d7CrossRefPubMed

68.

Aronne LJ, Halseth AE, Burns CM, Miller S, Shen LZ (2010) Enhanced weight loss following coadministration of pramlintide with sibutramine or phentermine in a multicenter trial. Obesity 18:1739–1746. https://doi.org/10.1038/oby.2009.478CrossRefPubMed

69.

Hendricks EJ, Rothman RB, Greenway FL (2009) How physician obesity specialists use drugs to treat obesity. Obesity 17:1730–1735. https://doi.org/10.1038/oby.2009.69CrossRefPubMed

70.

Bray GA, Greenway FL (2007) Pharmacological treatment of the overweight patient. Pharmacol Rev 59:151–184. https://doi.org/10.1124/pr.59.2.2CrossRefPubMed

71.

Roth JD, Trevaskis JL, Wilson J, Lei C, Athanacio J, Mack C, Kesty NC, Coffey T, Weyer C, Parkes DG (2008) Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats. Int J Obes 32:1201–1210. https://doi.org/10.1038/ijo.2008.91CrossRef

72.

Rocha T, Amaral JS, Oliveira MBPP (2016) Adulteration of dietary supplements by the illegal addition of synthetic drugs: a review. Compr Rev Food Sci Food Saf 15:43–62. https://doi.org/10.1111/1541-4337.12173CrossRefPubMed

73.

Ahmed N, Nounou MI, Abouelfetouh A, El-Kamel A (2019) Over-the-counter herbal weight loss supplements in Egypt: label claim, microbiological and pharmaceutical quality, and safety assessments. Med Princ Pract 28:167–177. https://doi.org/10.1159/000495986CrossRefPubMed

74.

García-Alonso D, Morgenstern-Kaplan D, Cohen-Welch A, Lozano-Cuenca J, López-Canales JS (2019) Possible mechanisms involved in the vasorelaxant effect produced by anorexigenic drugs in rat aortic rings. Med Sci 7:39. https://doi.org/10.3390/medsci7030039CrossRef

75.

López-Canales JS, Lozano-Cuenca J, Muãoz-Islas E, Aguilar-Carrasco JC, López-Canales OA, López-Mayorga RM, Castillo-Henkel EF, Valencia-Hernández I, Castillo-Henkel C (2015) Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings. Brazil J Med Biol Res 48:537–544. https://doi.org/10.1590/1414-431x20144261CrossRef

76.

De Carvalho LM, Cohen PA, Silva CV, Moreira APL, Falcão TM, Dal Molin TR, Zemolin G, Martini M (2012) A new approach to determining pharmacologic adulteration of herbal weight loss products. Food Addit Contam Part A 29:1661–1667. https://doi.org/10.1080/19440049.2012.706834CrossRef

77.

Almeida AE, Ribeiro ML, Polese L (2000) Determination of amfepramone hydrochloride, fenproporex, and diazepam in so-called “natural” capsules used in the treatment of obesity. J Liq Chromatogr Relat Technol 23:1109–1118. https://doi.org/10.1081/JLC-100101512CrossRef

78.

Suplicy H, Boguszewski CL, Dos Santos CMC, do Desterro de Figueiredo M, Cunha DR, Radominski R (2014) A comparative study of five centrally acting drugs on the pharmacological treatment of obesity. Int J Obes 38:1097–1103. https://doi.org/10.1038/ijo.2013.225CrossRef

79.

Abramowicz MJ, Van Haecke P, Demedts M, Delcroix M (2003) Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation. Eur Respir J 22:560–562. https://doi.org/10.1183/09031936.03.00095303CrossRefPubMed

80.

Cercato C, Roizenblatt VA, Leança CC, Segal A, Lopes Filho AP, Mancini MC, Halpern A (2009) A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects. Int J Obes 33:857–865. https://doi.org/10.1038/ijo.2009.124CrossRef

81.

Challman TD, Lipsky JJ (2000) Methylphenidate: its pharmacology and uses. Mayo Clin Proc 75:711–721. https://doi.org/10.4065/75.7.711CrossRefPubMed

82.

Volkow N-D, Fowler J-S, Wang G-J, Ding Y-S, Gatley S-J (2002) Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 6:31–43. https://doi.org/10.1177/070674370200601s05CrossRef

83.

Scahill L, Carroll D, Burke K (2004) Methylphenidate: mechanism of action and clinical update. J Child Adolesc Psychiatr Nurs 17:85–86. https://doi.org/10.1111/j.1744-6171.2004.00085.xCrossRefPubMed

84.

Chandramouli JB, Muller BA (2000) Case report of severe weight loss possibly associated with methylphenidate. J Pharm Technol 16:197–201. https://doi.org/10.1177/875512250001600503CrossRef

85.

Blankfield RP (2012) Blood pressure, fluid retention and the cardiovascular risk of drugs. Future Cardiol 8:489–493. https://doi.org/10.2217/fca.12.39CrossRefPubMed

86.

Goldman RD (2010) ADHD stimulants and their effect on height in children. Can Fam Physician 56:145–146 (PMID:20154245)PubMedPubMedCentral

87.

Wilens TE, Adler LA, Adams J, Sgambati S, Rotrosen J, Sawtelle R, Utzinger L, Fusillo S (2008) Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry 47:21–31. https://doi.org/10.1097/chi.0b013e31815a56f1CrossRefPubMed

88.

Deconinck E, Verlinde K, Courselle P, De Beer JO (2012) A validated ultra high pressure liquid chromatographic method for the characterisation of confiscated illegal slimming products containing anorexics. J Pharm Biomed Anal 59:38–43. https://doi.org/10.1016/j.jpba.2011.09.036CrossRefPubMed

89.

Vanhee C, Tuenter E, Kamugisha A, Canfyn M, Moens G, Courselle P, Pieters L, Deconinck E, Exarchou V (2018) Identification and quantification methodology for the analysis of suspected illegal dietary supplements: reference standard or no reference standard, that’s the question. J Forensic Toxicol Pharmacol 7:1. https://doi.org/10.4172/2325-9841.1000156CrossRef

90.

Billiard M (2003) Modafinil: pharmacology and therapeutic perspectives. Rev Neurol (Paris) 159:122–125 (in French)

91.

Chakravorty SS, Rye DB (2003) Narcolepsy in the older adult: epidemiology, diagnosis and management. Drugs Aging 20:361–376. https://doi.org/10.2165/00002512-200320050-00005CrossRefPubMed

92.

Czeisler CA, Walsh JK, Roth T, Hughes RJ, Wright KP, Kingsbury L, Arora S, Schwartz JRL, Niebler GE, Dinges DF (2005) Modafinil for excessive sleepiness associated with shift-work sleep disorder. N Engl J Med 353:476–486. https://doi.org/10.1056/NEJMoa041292CrossRefPubMed

93.

Keating GM, Raffin MJ (2005) Modafinil: a review of its use in excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder. CNS Drugs 19:785–803. https://doi.org/10.2165/00023210-200519090-00005CrossRefPubMed

94.

Ballon JS, Feifel D (2006) A systematic review of modafinil: potential clinical uses and mechanisms of action. J Clin Psychiatry 67:554–566. https://doi.org/10.4088/JCP.v67n0406CrossRefPubMed

95.

Makris AP, Rush CR, Frederich RC, Kelly TH (2004) Wake-promoting agents with different mechanisms of action: comparison of effects of modafinil and amphetamine on food intake and cardiovascular activity. Appetite 42:185–195. https://doi.org/10.1016/j.appet.2003.11.003CrossRefPubMed

96.

Kim D (2012) Practical use and risk of modafinil, a novel waking drug. Environ Health Toxicol 27:e2012007. https://doi.org/10.5620/eht.2012.27.e2012007CrossRefPubMedPubMedCentral

97.

Minzenberg MJ, Carter CS (2008) Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology 33:1477–1502. https://doi.org/10.1038/sj.npp.1301534CrossRefPubMed

98.

Lazenka MF, Negus SS (2017) Oral modafinil facilitates intracranial self-stimulation in rats. Behav Pharmacol 28:318–322. https://doi.org/10.1097/FBP.0000000000000288CrossRefPubMedPubMedCentral

99.

Avelar AJ, Cao J, Newman AH, Beckstead MJ (2017) Atypical dopamine transporter inhibitors R-modafinil and JHW 007 differentially affect D2 autoreceptor neurotransmission and the firing rate of midbrain dopamine neurons. Neuropharmacology 123:410–419. https://doi.org/10.1016/j.neuropharm.2017.06.016CrossRefPubMedPubMedCentral

100.

Aronson J (2016) Rimonabant. Meyler’s side effects of drugs, 16th edn. Elsevier, Amsterdam, pp 174–176. https://doi.org/10.1016/B978-0-444-53717-1.01712-1CrossRef

101.

Hossain MA, Pervin R, Debnath D, Bhuiyan MA (2019) Therapeutic treatment for controlling childhood obesity. In: Bagchi D (ed) Global perspectives on childhood obesity. Academic Press, Cambridge, pp 377–385CrossRef

102.

Ioannides-Demos LL, Piccenna L, McNeil JJ (2011) Pharmacotherapies for obesity: past, current, and future therapies. J Obes 2011:179674. https://doi.org/10.1155/2011/179674CrossRefPubMed

103.

Venhuis BJ, Vredenbregt MV, Kaun N, Maurin JK, Fijałek Z, de Kaste D (2011) The identification of rimonabant polymorphs, sibutramine and analogues of both in counterfeit Acomplia bought on the internet. J Pharm Biomed Anal 54:21–26. https://doi.org/10.1016/j.jpba.2010.07.043CrossRefPubMed

104.

Trakulsrichai S, Sathirakul K, Auparakkitanon S, Krongvorakul J, Sueajai J, Noumjad N, Sukasem C, Wananukul W, Limsila P (2015) Pharmacokinetics of mitragynine in man. Drug Des Devel Ther 9:2421–2429. https://doi.org/10.2147/DDDT.S79658(open access article)CrossRefPubMedPubMedCentral

105.

Harun N, Hassan Z, Navaratnam V, Mansor SM, Shoaib M (2015) Discriminative stimulus properties of mitragynine (kratom) in rats. Psychopharmacology 232:2227–2238. https://doi.org/10.1007/s00213-015-3866-5CrossRefPubMed

106.

Warner ML, Kaufman NC, Grundmann O (2016) The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Int J Legal Med 130:127–138. https://doi.org/10.1007/s00414-015-1279-yCrossRefPubMed

107.

Veltri C, Grundmann O (2019) Current perspectives on the impact of Kratom use. Subst Abuse Rehabil 10:23–31. https://doi.org/10.2147/sar.s164261(open access article)CrossRefPubMedPubMedCentral

108.

Manda VK, Avula B, Ali Z, Khan IA, Walker LA, Khan SI (2014) Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and mitraphylline. Planta Med 80:568–576. https://doi.org/10.1055/s-0034-1368444CrossRefPubMed

109.

Babu KM, McCurdy CR, Boyer EW (2008) Opioid receptors and legal highs: Salvia divinorum and Kratom. Clin Toxicol 46:146–152. https://doi.org/10.1080/15563650701241795CrossRef

110.

EMCDDA (2015) Kratom drug profile. http://www.emcdda.europa.eu/publications/drug-profiles/kratom#. Accessed 9 Jul 2015

111.

Simpson D (2013) Does Kratom cause weight loss?—Kratom online—buy Kratom capsules, powder and extract. https://kratomonline.org/kratom-weight-loss/. Accessed 3 Jun 2020

112.

Gunnar T, Ariniemi K, Lillsunde P (2005) Determination of 14 benzodiazepines and hydroxy metabolites, zaleplon and zolpidem as tert-butyldimethylsilyl derivatives compared with other common silylating reagents in whole blood by gas chromatography-mass spectrometry. J Chromatogr B 818:175–189. https://doi.org/10.1016/j.jchromb.2004.12.032CrossRef

113.

Billes SK, Sinnayah P, Cowley MA (2014) Naltrexone/bupropion for obesity: an investigational combination pharmacotherapy for weight loss. Pharmacol Res 84:1–11. https://doi.org/10.1016/j.phrs.2014.04.004CrossRef

114.

Cooper JA, Tucker VL, Papakostas GI (2014) Resolution of sleepiness and fatigue: a comparison of bupropion and selective serotonin reuptake inhibitors in subjects with major depressive disorder achieving remission at doses approved in the European Union. J Psychopharmacol 28:118–124. https://doi.org/10.1177/0269881113514878CrossRefPubMed

115.

Monson K, Schoenstadt A (2007) Wellbutrin XL and weight loss. http://depression.emedtv.com/wellbutrin-xl/wellbutrin-xl-and-weight-loss.html. Accessed 10 Jul 2015

116.

LeWine H (2014) FDA approves weight-loss drug Contrave. http://www.health.harvard.edu/blog/fda-approves-weight-loss-drug-contrave-201409127431. Accessed 10 Jul 2015

117.

Santarsieri D, Schwartz TL (2015) Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs Context 4:1–12. https://doi.org/10.7573/dic.212290CrossRef

118.

Phattanawasin P, Sotanaphun U, Sukwattanasinit T, Akkarawaranthorn J, Kitchaiya S (2012) Quantitative determination of sibutramine in adulterated herbal slimming formulations by TLC-image analysis method. Forensic Sci Int 219:96–100. https://doi.org/10.1016/j.forsciint.2011.12.004CrossRefPubMed

119.

Moreira APL, Motta MJ, Dal Molin TR, Viana C, de Carvalho LM (2013) Determination of diuretics and laxatives as adulterants in herbal formulations for weight loss. Food Addit Contam Part A 30:1230–1237. https://doi.org/10.1080/19440049.2013.800649CrossRef

120.

Cadwallader A-B, de La Torre X, Tieri A, Botrè F (2010) The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis. Br J Pharmacol 161:1–16. https://doi.org/10.1111/j.1476-5381.2010.00789.xCrossRefPubMedPubMedCentral

121.

Heckman MA, Weil J, de Mejia EG (2010) Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci 75:R77–R87. https://doi.org/10.1111/j.1750-3841.2010.01561.xCrossRefPubMed

122.

Onakpoya I, Hung SK, Perry R, Wider B, Ernst E (2011) The use of Garcinia extract (hydroxycitric acid) as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials. J Obes 2011:509038. https://doi.org/10.1155/2011/509038 (open access article)CrossRefPubMed

123.

Onakpoya I, Terry R, Ernst E (2011) The use of green coffee extract as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials. Gastroenterol Res Pract 2011:382852. https://doi.org/10.1155/2011/382852 (open access article)CrossRefPubMed

124.

Scheen AJ (2010) Cardiovascular risk-benefit profile of sibutramine. Am J Cardiovasc Drugs 10:321–334. https://doi.org/10.2165/11584800-000000000-00000CrossRefPubMed

125.

FDA (2018) FDA drug safety communication: FDA recommends against the continued use of Meridia (sibutramine). http://www.fda.gov/drugs/drugsafety/ucm228746.htm. Accessed 2 Jun 2020

126.

European Medicines Agency (EMA) (2010) Sibutramine. https://www.ema.europa.eu/en/medicines/human/referrals/sibutramine. Accessed 3 Jun 2020

127.

Australian Government. Department of Health. Therapeutic Goods Administration (TGA) (2010) Sibutramine (Reductil)—withdrawal in Australia. https://www.tga.gov.au/alert/sibutramine-reductil-withdrawal-australia. Accessed 2 Jun 2020

128.

James WPT, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL (2010) Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 363:905–917. https://doi.org/10.1056/NEJMoa1003114CrossRefPubMed

129.

FDA (1997) FDA announces withdrawal fenfluramine and dexfenfluramine (Fen-Phen). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm. Accessed 7 Jul 2015

130.

Sinclair N (2000) EC bans medicines containing anorectic agents. http://www.icis.com/resources/news/2000/03/27/108887/ec-bans-medicines-containing-anorectic-agents/. Accessed 8 Jul 2015

131.

Ball D, Kanter J (2003) European court overturns ban on a class of drugs for obesity. In: The Wall Str. J. http://www.wsj.com/articles/SB1043752981653832544. Accessed 8 Jul 2015

132.

Valsamakis G, Konstantakou P, Mastorakos G (2017) New targets for drug treatment of obesity. Annu Rev Pharmacol Toxicol 57:585–605. https://doi.org/10.1146/annurev-pharmtox-010716-104735CrossRefPubMed

133.

Sam AH, Salem V, Ghatei MA (2011) Rimonabant: from RIO to ban. J Obes 2011:432607. https://doi.org/10.1155/2011/432607 (open access article)CrossRefPubMedPubMedCentral

134.

EMCDDA (2015) New psychoactive substances in Europe. An update from EU Early Warning System. https://doi.org/10.2810/372415

135.

Mounteney J, Griffiths P, Sedefov R, Noor A, Vicente J, Simon R (2016) The drug situation in Europe: an overview of data available on illicit drugs and new psychoactive substances from European monitoring in 2015. Addiction 111:34–48. https://doi.org/10.1111/add.13056 (open access article)CrossRefPubMed

136.

Drug Enforcement Administration, Department of Justice (2016) Schedules of controlled substances: temporary placement of U-47700 into Schedule I. Final order. Fed Regist 81:79389–79393

137.

FDA (2018) Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom, underscoring its potential for abuse. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-scientific-evidence-presence-opioid-compounds. Accessed 3 Jun 2020

138.

Chan KB, Pakiam C, Rahim RA (2007) Psychoactive plant abuse: the identification of mitragynine in ketum and in ketum preparations. Bull Narc 57:249–256 (PMID:21338025)

139.

Martino R, Malet-Martino M, Gilard V, Balayssac S (2010) Counterfeit drugs: analytical techniques for their identification. Anal Bioanal Chem 398:77–92. https://doi.org/10.1007/s00216-010-3748-yCrossRefPubMed

140.

SafeMedicines (2010) Partnership for safe medicines applauds Google’s updated U.S. pharmaceutical advertising policy. http://www.safemedicines.org/2010/02/partnership-for-safe-medicines-applauds-googles-updated-us-pharmaceutical-advertising-policy.html. Accessed 8 Jun 2015

141.

FDA (2019) Tainted weight loss products. https://www.fda.gov/drugs/medication-health-fraud/tainted-weight-loss-products. Accessed 3 Nov 2020

142.

Palmer RB, Kim N-H, Dasgupta A (2000) Simultaneous determination of fenfluramine and phentermine in urine using gas chromatography mass spectrometry with pentafluoropropionic anhydride derivatization. Ther Drug Monit 22:418–422. https://doi.org/10.1097/00007691-200008000-00009CrossRefPubMed

143.

FDA (2016) FDA drug safety communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-warnings-regarding-use-diabetes-medicine-metformin-certain. Accessed 5 Sep 2020

144.

Bailey CJ (2017) Metformin: historical overview. Diabetologia 60:1566–1576. https://doi.org/10.1007/s00125-017-4318-zCrossRefPubMed

145.

Zhu Z, Jiang W, Thompson MD, Echeverria D, McGinley JN, Thompson HJ (2015) Effects of metformin, buformin, and phenformin on the post-initiation stage of chemically induced mammary carcinogenesis in the rat. Cancer Prev Res 8:518–527. https://doi.org/10.1158/1940-6207.CAPR-14-0121CrossRef

146.

Hankó B, Tukarcs É, Kumli P, Vincze Z (2005) Antidiabetic drug utilization in Hungary. Pharm World Sci 27:263–265. https://doi.org/10.1007/s11096-004-5804-1CrossRefPubMed

147.

Chou C-H, Cheng C-L, Huang C-C (2004) A validated HPLC method with ultraviolet detection for the determination of buformin in plasma. Biomed Chromatogr 18:254–258. https://doi.org/10.1002/bmc.312CrossRefPubMed

148.

Rubiño MEG, Carrillo E, Alcalá GR, Domínguez-Martín A, Marchal JA, Boulaiz H (2019) Phenformin as an anticancer agent: challenges and prospects. Int J Mol Sci 20:3316. https://doi.org/10.3390/ijms20133316 (open access article)CrossRef

149.

Ching CK, Lai CK, Poon WT, Wong ENP, Yan WW, Chan AYW, Mak TWL (2008) Hazards posed by a banned drug—phenformin is still hanging around. Hong Kong Med J 14:50–54 (PMID:18239244) (open access article)PubMed

150.

Home Office UK (2019) List of most commonly encountered drugs currently controlled under the misuse of drugs legislation. https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation. Accessed 6 Sep 2020

151.

Australian Government Department of Health, Therapeutic Goods Administration (2017) Scheduling delegate’s interim decisions and invitation for further comment: ACCS/ACMS, March and July 2017. https://www.tga.gov.au/book-page/15-alpha-pyrrolidinovalerophenone-alpha-pvp-and-related-substances-methylone-and-synthetic-cathinones. Accessed 6 Sep 2020

152.

Deutscher Bundestag (2011) Gesetzentwurf der Bundesregierung. http://dip21.bundestag.de/dip21/btd/18/025/1802581.pdf. Accessed 6 Sep 2020

153.

International narcotics control board (2003) List of psychotropic substance under international control. https://www.incb.org/documents/Psychotropics/forms/greenlist/Green_list_ENG_08673.pdf. Accessed 6 Sep 2020

154.

US Department of Justice (2016) Title 21 code of federal regulations: Part 1308—schedules of controlled substance. In: U.S. Dept. Justice, Drug Enforc. Adm., Diversion Control Division. https://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_12.htm. Accessed 6 Sep 2020

155.

Government of Canada, Department of Justice (2020) Controlled drugs and substances act (S.C 1996, c.19). https://laws-lois.justice.gc.ca/eng/acts/C-38.8/. Accessed 6 Sep 2020

156.

Australian Government, Federal Register of Legislation (2016) Poisons Standard July 2016 (F2016L01071). https://www.legislation.gov.au/Details/F2016L01071

157.

UK Government (1971) Misuse of Drugs Act 1971 (c. 38): SCHEDULE 2: controlled drugs. https://www.legislation.gov.uk/ukpga/1971/38/schedule/2/2019-04-01?timeline=true. Accessed 6 Sep 2020

158.

New Zealand Medicines and Medical Devices Safety Authority (2017) Restrictions on the supply, prescribing or administration of medicines under the Medicines Act 1981 and Misuse of Drugs Regulations 1977. https://www.medsafe.govt.nz/profs/riss/restrict.asp#Methylphenidate, https://www.medsafe.govt.nz/profs/riss/restrict.asp#Clozapine. Accessed 6 Sep 2020

159.

Swedish Ministry of Justice (1968) Narcotics penal code (1968: 64) (NSL). https://lagen.nu/1968:64. Accessed 6 Sep 2020

160.

Japanese Narcotic Control Department (2020) Situation of drug abuse. http://www.ncd.mhlw.go.jp/en/index.html. Accessed 7 Sep 2020

161.

Swedish Medical Products Agency (2019) Läkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika. https://www.lakemedelsverket.se/4aa752/globalassets/dokument/lagar-och-regler/hslf-fs/lvfs-2011-10-konsoliderad.pdf Accessed 7 Sep 2020

162.

Australian Government, Federal Register of Legislation (2020) Poisons standard July 2020 (F2020L00899). https://www.legislation.gov.au/Details/F2020L00899. Accessed 7 Sep 2020

163.

Zhou L, Wang X, Liu W, Xiang P, Chen H (2020) Rapid identification of the “smart drug” modafinil in suspicious tablets by DART-HRMS combined with micropunching. Anal Methods 12:1430–1440. https://doi.org/10.1039/c9ay02624jCrossRef

164.

Government of Russia Federation (1998) Decision of the Government of the Russian Federation of No. 681 of June 30, 1998 on approval of the list of narcotic drugs, psychotropic substances and their precursors that shall be subject to control in the Russian Federation. https://www.wto.org/english/thewto_e/acc_e/rus_e/WTACCRUS48A5_LEG_56.pdf. Accessed 7 Sep 2020

165.

US Department of Health and Human Services (2017) Basis for the recommendation to control mitragynine and 7-hydroxymitragynine in Schedule I of the controlled substances act. https://www.documentcloud.org/documents/5031552-HHS-kratom-letter.html. Accessed 7 Sep 2020

166.

New Zealand Legislation (2020) Medicines Regulations 1984 (SR 1984/143) (as of 1 April 2020). http://www.legislation.govt.nz/regulation/public/1984/0143/latest/DLM95668.html. Accessed 7 Sep 2020

167.

National Institute of Health Sciences of Japan (2020) List of “Designated Substances” in Japan. https://www.mhlw.go.jp/content/11120000/List.Nov.24.pdf. Accessed 17 Oct 2020

168.

Legislation.gov.uk (2020) Psychoactive Substances Act 2016. https://www.legislation.gov.uk/ukpga/2016/2/contents. Accessed 7 Sep 2020

169.

Strano-Rossi S, Colamonici C, Botrè F (2007) Detection of sibutramine administration: a gas chromatography/mass spectrometry study of the main urinary metabolites. Rapid Commun Mass Spectrom 21:79–88. https://doi.org/10.1002/rcm.2807CrossRefPubMed

170.

Ortiz RS, de Cássia MK, Holzschuh MH, Romão W, Limberger RP, Mayorga P (2013) Profiling counterfeit Cialis, Viagra and analogs by UPLC-MS. Forensic Sci Int 229:13–20. https://doi.org/10.1016/j.forsciint.2013.03.024CrossRefPubMed

171.

Csupor D, Boros K, Dankó B, Veres K, Szendrei K, Hohmann J (2013) Rapid identification of sibutramine in dietary supplements using a stepwise approach. Pharmazie 68:15–18. https://doi.org/10.1691/ph.2013.2069CrossRefPubMed

172.

de Freitas SC, dos Santos MAZ, Berneira LM, Ortiz RS, de Pereira CMP (2019) Microwave-assisted extraction and differential scanning calorimetry in the chemical identification of sliming agents apprehended in the south region of Brazil. Sci Justice 59:190–198. https://doi.org/10.1016/j.scijus.2018.11.001CrossRefPubMed

173.

Rasmussen KE, Pedersen-Bjergaard S, Krogh M, Grefslie Ugland H, Grønhaug T (2000) Development of a simple in-vial liquid-phase microextraction device for drug analysis compatible with capillary gas chromatography, capillary electrophoresis and high-performance liquid chromatography. J Chromatogr A 873:3–11. https://doi.org/10.1016/S0021-9673(99)01163-2CrossRefPubMed

174.

Ho TS, Pedersen-Bjergaard S, Rasmussen KE (2002) Recovery, enrichment and selectivity in liquid-phase microextraction: comparison with conventional liquid–liquid extraction. J Chromatogr A 963:3–17. https://doi.org/10.1016/S0021-9673(02)00215-7CrossRefPubMed

175.

Snow N-H (2000) Solid-phase micro-extraction of drugs from biological matrices. J Chromatogr A 885:445–455. https://doi.org/10.1016/S0021-9673(00)00192-8CrossRefPubMed

176.

Sporkert F, Pragst F (2000) Use of headspace solid-phase microextraction (HS-SPME) in hair analysis for organic compounds. Forensic Sci Int 107:129–148. https://doi.org/10.1016/S0379-0738(99)00158-9CrossRefPubMed

177.

Bielicka-Daszkiewicz K, Voelkel A (2009) Theoretical and experimental methods of determination of the breakthrough volume of SPE sorbents. Talanta 80:614–621. https://doi.org/10.1016/j.talanta.2009.07.037CrossRefPubMed

178.

Zhao L, Lee HK (2001) Application of static liquid-phase microextraction to the analysis of organochlorine pesticides in water. J Chromatogr A 919:381–388. https://doi.org/10.1016/S0021-9673(01)00816-0CrossRefPubMed

179.

Shen G, Lee HK (2002) Hollow fiber-protected liquid-phase microextraction of triazine herbicides. Anal Chem 74:648–654. https://doi.org/10.1021/ac010561oCrossRefPubMed

180.

Bae J-W, Choi C-I, Jang C-G, Lee S-Y (2011) Simultaneous determination of sibutramine and its active metabolites in human plasma by LC–MS/MS and its application to a pharmacokinetic study. Biomed Chromatogr 25:1181–1188. https://doi.org/10.1002/bmc.1587CrossRefPubMed

181.

Adaway JE, Keevil BG, Owen LJ (2015) Liquid chromatography tandem mass spectrometry in the clinical laboratory. Ann Clin Biochem 52:18–38. https://doi.org/10.1177/0004563214557678 (open access article)CrossRefPubMed

182.

Gathungu R-M, Kautz R, Kristal B-S, Bird S-S, Vouros P (2020) The integration of LC-MS and NMR for the analysis of low molecular weight trace analytes in complex matrices. Mass Spectrom Rev 39:35–54. https://doi.org/10.1002/mas.21575CrossRefPubMed

183.

Chesnut SM, Salisbury JJ (2007) The role of UHPLC in pharmaceutical development. J Sep Sci 30:1183–1190. https://doi.org/10.1002/jssc.200600505CrossRefPubMed

184.

Dong MW, Guillarme D (2013) Newer developments in HPLC impacting pharmaceutical analysis: a brief review. Am Pharm Rev 16:36–43 (open access article)

185.

Stypułkowska K, Błażewicz A, Maurin J, Sarna K, Fijałek Z (2011) X-ray powder diffractometry and liquid chromatography studies of sibutramine and its analogues content in herbal dietary supplements. J Pharm Biomed Anal 56:969–975. https://doi.org/10.1016/j.jpba.2011.08.028CrossRefPubMed

186.

Núñez O, Gallart-Ayala H, Martins CPB, Lucci P, Busquets R (2013) State-of-the-art in fast liquid chromatography-mass spectrometry for bio-analytical applications. J Chromatogr B 927:3–21. https://doi.org/10.1016/j.jchromb.2012.12.031CrossRef

187.

Jemal M (2000) High-throughput quantitative bioanalysis by LC/MS/MS. Biomed Chromatogr 14:422–429. https://doi.org/10.1002/1099-0801(200010)14:6%3c422::AID-BMC25%3e3.0.CO;2-ICrossRefPubMed

188.

Kim SH, Lee J, Yoon T, Choi J, Choi D, Kim D, Kwon SW (2009) Simultaneous determination of anti-diabetes/anti-obesity drugs by LC/PDA, and targeted analysis of sibutramine analog in dietary supplements by LC/MS/MS. Biomed Chromatogr 23:1259–1265. https://doi.org/10.1002/bmc.1248CrossRefPubMed

189.

Bogusz MJ, Hassan H, Al-Enazi E, Ibrahim Z, Al-Tufail M (2006) Application of LC-ESI-MS-MS for detection of synthetic adulterants in herbal remedies. J Pharm Biomed Anal 41:554–564. https://doi.org/10.1016/j.jpba.2005.12.015CrossRefPubMed

190.

Chen Y, Zhao L, Lu F, Yu Y, Chai Y, Wu Y (2009) Determination of synthetic drugs used to adulterate botanical dietary supplements using QTRAP LC-MS/MS. Food Addit Contam Part A 26:595–603. https://doi.org/10.1080/02652030802641880CrossRef

191.

Li Y, Zhang H, Hu J, Xue F, Li Y, Sun C (2012) A GC-EI-MS-MS method for simultaneous determination of seven adulterants in slimming functional foods. J Chromatogr Sci 50:928–933. https://doi.org/10.1093/chromsci/bms092CrossRefPubMed

192.

Arbouche N, Batt M-O, Raul J-S, Kintz P (2020) Development of a new GC–MS/MS method for the determination of metformin in human hair. Drug Test Anal 12:1380–1386. https://doi.org/10.1002/dta.2866CrossRefPubMed

193.

Goedecke C, Fettig I, Piechotta C, Philipp R, Geissen SU (2017) A novel GC-MS method for the determination and quantification of metformin in surface water. Anal Methods 9:1580–1584. https://doi.org/10.1039/C6AY02606KCrossRef

194.

Liu S-Y, Woo S-O, Koh H-L (2001) HPLC and GC–MS screening of Chinese proprietary medicine for undeclared therapeutic substances. J Pharm Biomed Anal 24:983–992. https://doi.org/10.1016/S0731-7085(00)00571-9CrossRefPubMed

195.

Che Sulaiman IS, Chieng BW, Pojol FE, Ong KK, Abdul Rashid JI, Wan Yunus WMZ, Mohd Kasim NA, Abdul Halim N, Mohd Noor SA, Knight VF (2020) A review on analysis methods for nerve agent hydrolysis products. Forensic Toxicol 38:297–313. https://doi.org/10.1007/s11419-019-00513-x(open access article)CrossRef

196.

Voeten RLC, Ventouri IK, Haselberg R, Somsen GW (2018) Capillary electrophoresis: trends and recent advances. Anal Chem 90:1464–1481. https://doi.org/10.1021/acs.analchem.8b00015 (open access article)CrossRefPubMedPubMedCentral

197.

Lamalle C, Marini RD, Debrus B, Lebrun P, Crommen J, Hubert P, Servais AC, Fillet M (2012) Development of a generic micellar electrokinetic chromatography method for the separation of 15 antimalarial drugs as a tool to detect medicine counterfeiting. Electrophoresis 33:1669–1678. https://doi.org/10.1002/elps.201100621CrossRefPubMed

198.

Marini RD, Rozet E, Montes MLA, Rohrbasser C, Roht S, Rhème D, Bonnabry P, Schappler J, Veuthey JL, Hubert P, Rudaz S (2010) Reliable low-cost capillary electrophoresis device for drug quality control and counterfeit medicines. J Pharm Biomed Anal 53:1278–1287. https://doi.org/10.1016/j.jpba.2010.07.026CrossRefPubMed

199.

Piette V, Parmentier F (2002) Analysis of illicit amphetamine seizures by capillary zone electrophoresis. J Chromatogr A 979:345–352. https://doi.org/10.1016/s0021-9673(02)01405-xCrossRefPubMed

200.

Akamatsu S, Mitsuhashi T (2014) Simultaneous determination of pharmaceutical components in dietary supplements for weight loss by capillary electrophoresis tandem mass spectrometry. Drug Test Anal 6:426–433. https://doi.org/10.1002/dta.1524CrossRefPubMed

201.

dos Santos VB, Daniel D, Singh M, do Lago CL (2016) Amphetamine and derivatives in natural weight loss pills and dietary supplements by capillary electrophoresis-tandem mass spectrometry. J Chromatogr B 1038:19–25. https://doi.org/10.1016/j.jchromb.2016.10.019CrossRef

202.

Deconinck E, Sacré P-Y, Courselle P, De Beer JO (2013) Chromatography in the detection and characterization of illegal pharmaceutical preparations. J Chromatogr Sci 51:791–806. https://doi.org/10.1093/chromsci/bmt006CrossRefPubMed

203.

Rocco A, Donati E, Touloupakis E, Aturki Z (2018) Miniaturized separation techniques as analytical methods to ensure quality and safety of dietary supplements. TrAC Trends Anal Chem 103:156–183. https://doi.org/10.1016/j.trac.2018.04.004CrossRef

204.

Toudeshki RM, Dadfarnia S, Haji Shabani AM (2019) Surface molecularly imprinted polymer on magnetic multi-walled carbon nanotubes for selective recognition and preconcentration of metformin in biological fluids prior to its sensitive chemiluminescence determination: central composite design optimization. Anal Chim Acta 1089:78–89. https://doi.org/10.1016/j.aca.2019.08.070CrossRefPubMed

205.

Song A, Wang J, Lu G, Jia Z, Yang J, Shi E (2018) Oxidized multiwalled carbon nanotubes coated fibers for headspace solid-phase microextraction of amphetamine-type stimulants in human urine. Forensic Sci Int 290:49–55. https://doi.org/10.1016/j.forsciint.2018.06.031CrossRefPubMed

206.

UNODC Global SMART programme (2013) The challenge of new psychoactive substances. https://www.unodc.org/documents/scientific/NPS_Report.pdf. Accessed 7 Sep 2020

207.

Alshaikhi AM, Alharthi N, Alzhrani S (2018) Sibutramine (hidden ingredient)—induced psychosis, associated with the use of herbal slimmingproduct: a case report. J Psychol Neuropsychiatry Std 1:101 (open access article)

208.

Bunya N, Sawamoto K, Uemura S, Kyan R, Inoue H, Nishida J, Kouzu H, Kokubu N, Miura T, Narimatsu E (2017) Cardiac arrest caused by sibutramine obtained over the Internet: a case of a young woman without pre-existing cardiovascular disease successfully resuscitated using extracorporeal membrane oxygenation. Acute Med Surg 4:334–337.https://doi.org/10.1002/ams2.275 (open access article)CrossRefPubMedPubMedCentral

209.

Shapira B, Goldstein L, Reshef A, Poperno A (2016) A rare case of psychomotor disturbances linked to the use of an adulterated dietary supplement containing sibutramine. Clin Neuropharmacol 39:154–156. https://doi.org/10.1097/WNF.0000000000000141CrossRefPubMed

210.

Pamukcu Gunaydin G, Dogan NO, Levent S, Kurtoglu Celik G (2015) Herbal weight loss pill overdose: sibutramine hidden in pepper pill. Case Rep Emerg Med 2015:213874. https://doi.org/10.1155/2015/213874 (open access article)CrossRef

211.

Vecchio S, Giampreti A, Petrolini V-M, Lonati D, Protti A, Papa P, Rognoni C, Valli A, Rocchi L, Rolandi L, Manzo L, Locatelli C-A (2014) Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol 52:129–135. https://doi.org/10.3109/15563650.2013.860985CrossRef

212.

Khazan M, Hedayati M, Askari S, Azizi F (2013) Adulteration of products sold as Chinese herbal medicines for weight loss with thyroid hormones and PCP. J Herb Med 3:39–43. https://doi.org/10.1016/j.hermed.2012.11.003CrossRef

213.

Heo SH, Kang M-H (2013) A case of dilated cardiomyopathy with massive left ventricular thrombus after Use of a sibutramine-containing slimming product. Korean Circ J 43:632–635. https://doi.org/10.4070/kcj.2013.43.9.632 (open access article)CrossRefPubMedPubMedCentral

214.

Lam PK, Leung KS, Wong TW, Lee HHC, Tang MHY, Mak TWL (2012) Serotonin syndrome following overdose of a non-prescription slimming product containing sibutramine: a case report. Hum Exp Toxicol 31:414–417. https://doi.org/10.1177/0960327111431704CrossRefPubMed

215.

Ching CK, Lam YH, Chan AYW, Mak TWL (2012) Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong. Br J Clin Pharmacol 73:795–800. https://doi.org/10.1111/j.1365-2125.2011.04135.x (open access article)CrossRefPubMed

216.

Vitalone A, Menniti-Ippolito F, Moro PA, Firenzuoli F, Raschetti R, Mazzanti G (2011) Suspected adverse reactions associated with herbal products used for weight loss: a case series reported to the Italian National Institute of Health. Eur J Clin Pharmacol 67:215–224. https://doi.org/10.1007/s00228-010-0981-4CrossRefPubMed

217.

Chong CSY (2010) Psychosis related to the use of sibutramine disguised as over-the-counter herbal weight loss remedies: a report of two patients. East Asian Arch Psychiatry 20:186–189 (PMID:22348928) (open access article)PubMed

218.

Müller D, Weinmann W, Hermanns-Clausen M (2009) Chinese slimming capsules containing sibutramine sold over the Internet. Dtsch Arztebl Int 106:218–222. https://doi.org/10.3238/arztebl.2009.0218 (open access article)CrossRefPubMedPubMedCentral

219.

Yim K-MA, Ng HW, Chan C-K, Yip G, Lau FL (2008) Sibutramine-induced acute myocardial infarction in a young lady. Clin Toxicol 46:877–879. https://doi.org/10.1080/15563650802136258 (open access article)CrossRef

220.

Poon WT, Ng SW, Lai CK, Chan YW, Mak WL (2008) Factitious thyrotoxicosis and herbal dietary supplement for weight reduction. Clin Toxicol 46:290–292. https://doi.org/10.1080/15563650701381179CrossRef

221.

Hung Y-M, Chang J-C (2006) Weight-reducing regimen associated with polymorphic ventricular tachycardia. Am J Emerg Med 24:714–716. https://doi.org/10.1016/j.ajem.2006.02.004CrossRefPubMed

222.

Jung J, Hermanns-Clausen M, Weinmann W (2006) Anorectic sibutramine detected in a Chinese herbal drug for weight loss. Forensic Sci Int 161:221–222. https://doi.org/10.1016/j.forsciint.2006.02.052CrossRefPubMed

223.

Lai V, Smith A, Thorburn D, Raman VS (2006) Severe hepatic injury and adulterated Chinese medicines. Br Med J 332:304–305. https://doi.org/10.1136/bmj.332.7536.304-bCrossRef

224.

Hsiao AL, Santucci KA, Seo-Mayer P, Mariappan MR, Hodsdon ME, Banasiak KJ, Baum CR (2005) Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a “dietary supplement.” Clin Toxicol 43:281–285. https://doi.org/10.1081/CLT-58946CrossRef

225.

Lau G, Lo DST, Yao YJ, Leong HT, Chan CL, Chu SS (2004) A fatal case of hepatic failure possibly induced by nitrosofenfluramine. Med Sci Law 44:252–263. https://doi.org/10.1258/rsmmsl.44.3.252CrossRefPubMed

226.

Adachi M, Saito H, Kobayashi H, Horie Y, Kato S, Yoshioka M, Ishii H (2003) Hepatic injury in 12 patients taking the herbal weight loss aids Chaso or Onshido. Ann Intern Med 139:488. https://doi.org/10.7326/0003-4819-139-6-200309160-00012CrossRefPubMed

227.

Nakadai A, Inagaki H, Minami M, Takahashi H, Namme R, Ohsawa M, Ikegami S (2003) Determination of the optical purity of N-nitrosofenfluramine found in the Chinese slimming diet. Yakugaku Zasshi 123:805–809. https://doi.org/10.1248/yakushi.123.805(in Japanese with English abstract; open access article)CrossRefPubMed

228.

Corns C, Metcalfe K (2002) Risks associated with herbal slimming remedies. J R Soc Promot Health 122:213–219. https://doi.org/10.1177/146642400212200407CrossRefPubMed

229.

Ali R, Alminderej FM, Saleh SM (2020) A simple, quantitative method for spectroscopic detection of metformin using gold nanoclusters. Spectrochim Acta A Mol Biomol Spectrosc 241:118744. https://doi.org/10.1016/j.saa.2020.118744CrossRefPubMed

230.

Moradi M, Sohrabi MR, Mortazavinik S (2020) Simultaneous ultra-trace quantitative colorimetric determination of antidiabetic drugs based on gold nanoparticles aggregation using multivariate calibration and neural network methods. Spectrochim Acta Part A Mol Biomol Spectrosc 234:118254. https://doi.org/10.1016/j.saa.2020.118254CrossRef

231.

Ma D, Quan J, Du J (2014) Gold nanoparticles-enhanced chemiluminescence determination of fenfluramine. J Chin Chem Soc 61:425–431. https://doi.org/10.1002/jccs.201300407CrossRef

232.

Pundir CS, Deswal R, Narwal V, Narang J (2018) Quantitative analysis of metformin with special emphasis on sensors: a review. Curr Anal Chem 14:438–445. https://doi.org/10.2174/1573411013666170907150509 (open access article)CrossRef

233.

Ghanbari MH, Sharafi P, Nayebossadr S, Norouzi Z (2020) Utilizing a nanocomposite consisting of zinc ferrite, copper oxide, and gold nanoparticles in the fabrication of a metformin electrochemical sensor supported on a glassy carbon electrode. Microchim Acta 187:557. https://doi.org/10.1007/s00604-020-04529-8CrossRef

234.

dos Santos WTP, Compton RG (2019) A simple method to detect the stimulant modafinil in authentic saliva using a carbon-nanotube screen-printed electrode with adsorptive stripping voltammetry. Sens Actuators B Chem 285:137–144. https://doi.org/10.1016/j.snb.2019.01.047CrossRef

Title: Counterfeit formulations: analytical perspective on anorectics
Authors: Dan Osei Mensah Bonsu
Constance Afoakwah
Maria de la Paz Aguilar-Caballos
Publication date: 01-01-2021
Publisher: Springer Singapore
Published in: Forensic Toxicology / Issue 1/2021
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-020-00564-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Counterfeit formulations: analytical perspective on anorectics

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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