Top

Forensic Toxicology

Published in:

31-01-2023 | Ambroxol | Original Article

Liquid chromatography with tandem mass spectrometric method for determination of 425 drugs and poisons in dried blood spots and application to forensic cases

Authors: Caixia Guo, Hui Yan, Wei Liu, Ping Xiang, Bin Di, Min Shen

Published in: Forensic Toxicology | Issue 2/2023

Abstract

Purpose

An analytical method using liquid chromatography with tandem mass spectrometry (LC–MS/MS) was established and validated for screening 425 drugs and poisons in dried blood spots (DBSs).

Methods

Blood (20 μL) was spotted on Whatman FTA™ classic card to prepare DBS sample, then extracted with 150 μL methanol and analyzed by LC–MS/MS using a multiple reaction monitoring method.

Results

The limit of detection of the compounds were 0.1–10 ng/mL. The values for recovery and matrix effect were 40.3–114.9% and 40.2–118.4%, respectively. This method was successfully applied to DBS samples from 105 humans suspected of drug poisoning, which was stored for 3–5 years at room temperature. Thirty-three kinds of drugs, including benzodiazepines, antipsychotics, antidepressants, antipyretic analgesics, non-steroidal anti-inflammatory drugs, antibiotics, antiepileptic drugs, new psychoactive drugs were confirmed in 102 cases, while no compound was detected in the other 3 cases. Estazolam, a benzodiazepine widely used in clinical practice as a sedative, hypnotic, and anti-anxiety drug, was the most frequently detected substance, occurring in 34.2% of the cases.

Conclusions

Most drugs in DBS could still be detected after storage for 3–5 years, but ambroxol, zopiclone, carbofuran, chlorpyrifos, and valproic acid were not detectable after 3–5 years of storage at room temperature. The components measured in DBS were consistent with those measured in whole blood at the collection time, thereby confirming that DBS samples have the advantage of stable storage at room temperature.

Available only for authorised users

Lee HL, Lin HJ, Yeh TY (2004) The epidemiology and prognostic factors of poisoning. Epidemiology 15:179–180 CrossRef

Tangiisuran B, Jiva M, Ariff AM, Abdul Rani NA, Misnan A, Rashid SM, Majid M, Dawson AH (2018) Evaluation of types of poisoning exposure calls managed by the Malaysia National Poison Centre (2006–2015): a retrospective review. BMJ Open 8:E024162. https://doi.org/10.1136/bmjopen-2018-024162 CrossRefPubMedPubMedCentral

Sadones N, Capiau S, De Kesel PM, Lambert WE, Stove CP (2014) Spot them in the spot: analysis of abused substances using dried blood spots. Bioanalysis 6:2211–2227. https://doi.org/10.4155/bio.14.156 CrossRefPubMed

Stove CP, Ingels AS, De Kesel PM, Lambert WE (2012) Dried blood spots in toxicology: from the cradle to the grave. Crit Rev Toxicol 42:230–243. https://doi.org/10.3109/10408444.2011.650790 CrossRefPubMed

Scriver CC (1963) A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 32:318–343

Li W, Tse FL (2010) Dried blood spot sampling in combination with LC–MS/MS for quantitative analysis of small molecules. Biomed Chromatogr 24:49–65. https://doi.org/10.1002/bmc.1367 CrossRefPubMed

Odoardi S, Anzillotti L, Strano-Rossi S (2014) Simplifying sample pretreatment: application of dried blood spot (DBS) method to blood samples, including postmortem, for UHPLC-MS/MS analysis of drugs of abuse. Forensic Sci Int 243:61–67. https://doi.org/10.1016/j.forsciint.2014.04.015 CrossRefPubMed

Velghe S, Deprez S, Stove CP (2019) Fully automated therapeutic drug monitoring of anti-epileptic drugs making use of dried blood spots. J Chromatogr A 1601:95–103. https://doi.org/10.1016/j.chroma.2019.06.022 CrossRefPubMed

Edelbroek PM, Heijden VD, Stolk LM (2009) Dried blood spot methods in therapeutic drug monitoring: methods, assays, and pitfalls. Ther Drug Monit 31:327–336. https://doi.org/10.1097/FTD.0b013e31819e91ce CrossRefPubMed

10.

Cho HD, Kim J, Lee JY, Kim YY, Lee Y, Jo E, Suh JH, Lee J, Cha S, Han SB (2020) A novel dried blood spots analysis combined with on-spot reaction for determination of trimethylamine N-oxide and its related compounds. Talanta 210:120639. https://doi.org/10.1016/j.talanta.2019.120639 CrossRefPubMed

11.

Joye T, SidibéJ DJ, Karmime A, Sporkert F, Widmer C, Favrat B, Lescuyer P, Augsburger M, Thomas A (2019) Liquid chromatography-high resolution mass spectrometry for broad-spectrum drug screening of dried blood spot as microsampling procedure. Anal Chim Acta 1063:110–116. https://doi.org/10.1016/j.aca.2019.02.011 CrossRefPubMed

12.

Protti M, Rudge J, Sberna AE, Gerra G, Mercolini L (2017) Dried haematic microsamples and LC-MS/MS for the analysis of natural and synthetic cannabinoids. J Chromatogr B 1044–1045:77–86. https://doi.org/10.1016/j.jchromb.2016.12.038 CrossRef

13.

Wagner M, Tonoli D, Varesio E, Hopfgartner G (2014) The use of mass spectrometry to analyze dried blood spots. Mass Spectrom Rev 35:361–438. https://doi.org/10.1002/mas.21441 CrossRefPubMed

14.

Maurer HH (2005) Multi-analyte procedures for screening for and quantification of drugs in blood, plasma, or serum by liquid chromatography-single stage or tandem mass spectrometry (LC-MS or LC-MS/MS) relevant to clinical and forensic toxicology. Clin Biochem 38:310–318. https://doi.org/10.1016/j.clinbiochem.2005.01.014 CrossRefPubMed

15.

Maurer HH (2005) Advances in analytical toxicology: the current role of liquid chromatography-mass spectrometry in drug quantification in blood and oral fluid. Anal Bioanal Chem 381:110–118. https://doi.org/10.1007/s00216-004-2774-z CrossRefPubMed

16.

Bjørk MK, Nielsen MK, Nielsen HB, Markussen L, Klinke HB, Linnet K (2010) Determination of 19 drugs of abuse and metabolites in whole blood by high-performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem 396:2393–2401. https://doi.org/10.1007/s00216-009-3268-9 CrossRefPubMed

17.

Decaestecker TN, Lambert WE, Van Peteghem CH, Deforce D, Van Bocxlaer JF (2004) Optimization of solid-phase extraction for a liquid chromatographic-tandem mass spectrometric general unknown screening procedure by means of computational techniques. J Chromatogr A 1056:57–65. https://doi.org/10.1016/j.chroma.2004.06.010 CrossRefPubMed

18.

Sergi M, Bafile E, Compagnone D, Curini R, D’Ascenzo G, Romolo FS (2009) Multiclass analysis of illicit drugs in plasma and oral fluids by LC-MS/MS. Anal Bioanal Chem 393:709–718. https://doi.org/10.1007/s00216-008-2456-3 CrossRefPubMed

19.

Bassan DM, Erdmann F, Krüll R (2011) Quantitative determination of 43 common drugs and drugs of abuse in human serum by HPLC-MS/MS. Anal Bioanal Chem 400:43–50. https://doi.org/10.1007/s00216-011-4784-y CrossRefPubMed

20.

Wissenbach DK, Meyer MR, Remane D, Weber AA, Maurer HH (2011) Development of the first metabolite-based LC-MS(n) urine drug screening procedure-exemplified for antidepressants. Anal Bioanal Chem 400:79–88. https://doi.org/10.1007/s00216-010-4398-9 CrossRefPubMed

21.

Dresen S, Ferreirós N, Gnann H, Zimmermann R, Weinmann W (2010) Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching. Anal Bioanal Chem 396:2425–2434. https://doi.org/10.1007/s00216-010-3485-2 CrossRefPubMed

22.

Broecker S, Herre S, Wüst B, Zweigenbaum J, Pragst F (2011) Development and practical application of a library of CID accurate mass spectra of more than 2,500 toxic compounds for systematic toxicological analysis by LC-QTOF-MS with data-dependent acquisition. Anal Bioanal Chem 400:101–117. https://doi.org/10.1007/s00216-010-4450-9 CrossRefPubMed

23.

Liu HC, Liu RH, Lin DL, Ho HO (2010) Rapid screening and confirmation of drugs and toxic compounds in biological specimens using liquid chromatography/ion trap tandem mass spectrometry and automated library search. Rapid Commun Mass Spectrom 24:75–84. https://doi.org/10.1002/rcm.4365 CrossRefPubMed

24.

Couchman L, Morgan PE (2011) LC-MS in analytical toxicology: some practical considerations. Biomed Chromatogr 25:100–123. https://doi.org/10.1002/bmc.1566 CrossRefPubMed

25.

Johnson RD, Botch SR (2011) The screening of forensic blood, urine, and tissue specimens for xenobiotics using ion-trap liquid chromatography-tandem mass spectrometry. J Anal Toxicol 35:65–74. https://doi.org/10.1093/anatox/35.2.65 CrossRefPubMed

26.

Luginbühl M, Gaugler S (2020) The application of fully automated dried blood spot analysis for liquid chromatography-tandem mass spectrometry using the CAMAG DBS-MS 500 autosampler. Clin Biochem 82:33–39. https://doi.org/10.1016/j.clinbiochem.2020.02.007 CrossRefPubMed

27.

Remane D, Meyer MR, Wissenbach DK, Maurer HH (2011) Ultra high performance liquid chromatographic-tandem mass spectrometric multi-analyte procedure for target screening and quantification in human blood plasma: validation and application for 31 neuroleptics, 28 benzodiazepines, and Z-drugs. Anal Bioanal Chem 401:1341–1352. https://doi.org/10.1007/s00216-011-5187-9 CrossRefPubMed

28.

Remane D, Meyer MR, Peters FT, Wissenbach DK, Maurer HH (2010) Fast and simple procedure for liquid-liquid extraction of 136 analytes from different drug classes for development of a liquid chromatographic-tandem mass spectrometric quantification method in human blood plasma. Anal Bioanal Chem 397:2303–2314. https://doi.org/10.1007/s00216-010-3820-7 CrossRefPubMed

29.

Quraishi R, Jain R, Ambekar A (2013) The use of dried blood spot samples in screening drugs of abuse. Pharmacol Pharm 4:152–159 CrossRef

30.

Rosano TG, Wood M, Swift TA (2011) Postmortem drug screening by non-targeted and targeted ultra-performance liquid chromatography-mass spectrometry technology. J Anal Toxicol 35:411–423. https://doi.org/10.1093/anatox/35.7.411 CrossRefPubMed

31.

Gaugler S, Al-Mazroua MK, Issa SY, Rykl J, Grill M, QanairA CVL (2019) Fully automated forensic routine dried blood spot screening for workplace testing. J Anal Toxicol 43:212–220 ( 093/jat/bky074) CrossRefPubMed

32.

Shen M, Xiang P, Shen BH, Ma D, Yan H (2006) Screening for 132 drugs in blood by LC-MS/MS with multiple reaction monitoring. Chin J of Forensic Sci 1:14–20

33.

Mueller CA, Weinmann W, Dresen S, Schreiber A, Gergov M (2005) Development of a multi-target screening analysis for 301 drugs using a QT rap liquid chromatography/tandem mass spectrometry system and automated library searching. Rapid Commun Mass Spectrom 19:1332–1339. https://doi.org/10.1002/rcm.1934 CrossRefPubMed

34.

Ambach L, Hernández Redondo A, König S, Weinmann W (2013) Rapid and simple LC-MS/MS screening of 64 novel psychoactive substances using dried blood spots. Drug Test Anal 6:367–375. https://doi.org/10.1002/dta.1505 CrossRefPubMed

35.

FDA (2018) Bioanalytical method validation guidance for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioanalytical-method-validation-guidance-industry/. Accessed 24 May 2018

36.

Yan X, Yuan S, Yu Z, Zhao Y, Zhang S, Wu H, Yan H, Xiang P (2020) Development of an LC-MS/MS method for determining 5-MeO-DIPT in dried urine spots and application to forensic cases. J Forensic Leg Med 72:101963. https://doi.org/10.1016/j.jflm.2020.101963 CrossRefPubMed

37.

Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 75:3019–3030. https://doi.org/10.1021/ac020361s CrossRefPubMed

38.

Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224. https://doi.org/10.1016/j.forsciint.2006.05.021 CrossRefPubMed

39.

Dib J, Tretzel L, Piper T, Lagojda A, Kuehne D, Schänzer W, Thevis M (2017) Screening for adiponectin receptor agonists and their metabolites in urine and dried blood spots. Clin Mass Spectrom 6:13–20. https://doi.org/10.1016/j.clinms.2017.10.002 CrossRef

40.

Schulz M, Schmoldt A, Andresen-Streichert H, Iwersen-Bergmann S (2020) Revisited: therapeutic and toxic blood concentrations of more than 1100 drugs and other xenobiotics. Crit Care 24:1–4. https://doi.org/10.1186/s13054-020-02915-5 CrossRef

41.

Nilsson GH, Kugelberg FC, Kronstrand R, Ahlner J (2010) Stability tests of zopiclone in whole blood. Forensic Sci Int 200:130–135. https://doi.org/10.1016/j.forsciint.2010.04.001 CrossRefPubMed

42.

Zhu M, Wang B (2015) Effects of intravenous lidocaine in patients with organophosphate poisoning associated with respiratory failure. Med J West China 27:1854–1856. https://doi.org/10.3969/j.issn.1672-3511.2015.12.028 CrossRef

Title: Liquid chromatography with tandem mass spectrometric method for determination of 425 drugs and poisons in dried blood spots and application to forensic cases
Authors: Caixia Guo
Hui Yan
Wei Liu
Ping Xiang
Bin Di
Min Shen
Publication date: 31-01-2023
Publisher: Springer Nature Singapore
Keywords: Ambroxol
Intoxication
Benzodiazepine
Zopiclone
Published in: Forensic Toxicology / Issue 2/2023
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-023-00659-9

Keynote Webinar | Spotlight on Diet and Diabetes

Springer Medicine

Liquid chromatography with tandem mass spectrometric method for determination of 425 drugs and poisons in dried blood spots and application to forensic cases

Abstract

Purpose

Methods

Results

Conclusions

Keynote Webinar | Spotlight on Diet and Diabetes

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2023

Δ9-Tetrahydrocannabinol stimulation of estrogen receptor-positive MCF-7 breast cancer cell migration: Interfering interaction with the estrogenic milieu

Urinary profiles of methoxyphenamine and its metabolite after inhalation of methoxyphenamine smoke in humans: aiming to distinguish between active and passive exposure

Cannabidiol in urine is not a proof of CBD consumption—lesson learned from urine sample analysis in routine caseworks

Detection of lisdexamfetamine and its metabolite d-amphetamine in urine and gastric contents collected from a cadaver at forensic autopsy

Quantification of olanzapine and its three metabolites by liquid chromatography–tandem mass spectrometry in human body fluids obtained from four deceased, and confirmation of the reduction from olanzapine N-oxide to olanzapine in whole blood in vitro

Analytical characterization and differentiation between threo- and erythro-4-fluoroethylphenidate