Skip to main content
Top
Published in: Forensic Toxicology 2/2016

01-07-2016 | Original Article

Simultaneous determination of cyclic antidepressants and their related drugs and the estimation of new metabolites in human whole blood and urine by MALDI-QTOF-mass spectrometry

Authors: Hideki Nozawa, Kayoko Minakata, Itaru Yamagishi, Koutaro Hasegawa, Masako Suzuki, Kunio Gonmori, Osamu Suzuki, Kanako Watanabe

Published in: Forensic Toxicology | Issue 2/2016

Login to get access

Abstract

A rapid and sensitive method using matrix-assisted laser desorption ionization (MALDI)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS) was developed for the analysis of six tricyclic antidepressants (ADs) and their related drugs, such as amitriptyline, carbamazepine, clomipramine, imipramine, nortriptyline, quetiapine, and two tetracyclic ADs, mianserin and mirtazapine, because these eight drugs are commonly observed medicines in poisoning cases in Japan. In the present MALDI-MS method, the limits of detection were 0.3–2 ng/mL. The present method provided a simple and high throughput simultaneous analysis of these drugs. This is the first report dealing with quantitation of ADs and their related drugs in biological samples by MALDI-MS. In addition, we applied the MALDI-MS to two authentic cases, and three new metabolites of amitriptyline and three new metabolites of quetiapine could be detected in blood and urine samples in the two cases when regioisomers were counted as one metabolite.
Literature
1.
go back to reference Kudo K, Ishida T, Hikiji W, Usumoto Y, Umehara T, Nagamatsu K, Tsuji A, Ikeda N (2010) Pattern of poisoning in Japan: selection of drugs and poisons for systematic toxicological analysis. Forensic Toxicol 28:25–32CrossRef Kudo K, Ishida T, Hikiji W, Usumoto Y, Umehara T, Nagamatsu K, Tsuji A, Ikeda N (2010) Pattern of poisoning in Japan: selection of drugs and poisons for systematic toxicological analysis. Forensic Toxicol 28:25–32CrossRef
2.
go back to reference Hayashi D, Kumazawa T, Hasegawa C, Lee X-P, Marumo A, Uchigasaki S, Kawamura M, Sato K (2012) A simple and reliable method for quantifying plasma concentrations of tetracyclic antidepressants using monolithic silica solid-phase extraction tips. Forensic Toxicol 30:98–105CrossRef Hayashi D, Kumazawa T, Hasegawa C, Lee X-P, Marumo A, Uchigasaki S, Kawamura M, Sato K (2012) A simple and reliable method for quantifying plasma concentrations of tetracyclic antidepressants using monolithic silica solid-phase extraction tips. Forensic Toxicol 30:98–105CrossRef
3.
go back to reference Papoutsis I, Khraiwesh A, Nikolaou P, Pistos C, Spiliopoulou C, Athanaselis S (2012) A fully validated method for the simultaneous determination of 11 antidepressant drugs in whole blood by gas chromatography-mass spectrometry. J Pharm Biomed Anal 70:557–562CrossRefPubMed Papoutsis I, Khraiwesh A, Nikolaou P, Pistos C, Spiliopoulou C, Athanaselis S (2012) A fully validated method for the simultaneous determination of 11 antidepressant drugs in whole blood by gas chromatography-mass spectrometry. J Pharm Biomed Anal 70:557–562CrossRefPubMed
4.
go back to reference Pietracci E, Bermejo A-M, Álvarez I, Cabarcos P, Balduini W, Tabernero M-J (2013) Simultaneous determination of new-generation antidepressants in plasma by gas chromatography-mass spectrometry. Forensic Toxicol 31:124–132CrossRef Pietracci E, Bermejo A-M, Álvarez I, Cabarcos P, Balduini W, Tabernero M-J (2013) Simultaneous determination of new-generation antidepressants in plasma by gas chromatography-mass spectrometry. Forensic Toxicol 31:124–132CrossRef
5.
go back to reference Breaud AR, Harlan R, Kozak M, Clarke W (2009) A rapid and reliable method for the quantitation of tricyclic antidepressants in serum using HPLC-MS/MS. Clin Biochem 42:1300–1307CrossRefPubMed Breaud AR, Harlan R, Kozak M, Clarke W (2009) A rapid and reliable method for the quantitation of tricyclic antidepressants in serum using HPLC-MS/MS. Clin Biochem 42:1300–1307CrossRefPubMed
6.
go back to reference Breaud AR, Harlan R, Di Bussolo JM, McMillin GA, Clarke W (2010) A rapid and fully-automated method for the quantitation of tricyclic antidepressants in serum using turbulent-flow liquid chromatography-tandem mass spectrometry. Clin Chim Acta 411:825–832CrossRefPubMed Breaud AR, Harlan R, Di Bussolo JM, McMillin GA, Clarke W (2010) A rapid and fully-automated method for the quantitation of tricyclic antidepressants in serum using turbulent-flow liquid chromatography-tandem mass spectrometry. Clin Chim Acta 411:825–832CrossRefPubMed
7.
go back to reference Hasselstrøm J (2011) Quantification of antidepressants and antipsychotics in human serum by precipitation and ultra high pressure liquid chromatography-tandem mass spectrometry. J Chromatogr B 879:123–128CrossRef Hasselstrøm J (2011) Quantification of antidepressants and antipsychotics in human serum by precipitation and ultra high pressure liquid chromatography-tandem mass spectrometry. J Chromatogr B 879:123–128CrossRef
8.
go back to reference Amundsen I, Øiestad ÅML, Ekeberg D, Kristoffersen L (2013) Quantitative determination of fifteen basic pharmaceuticals in ante- and post-mortem whole blood by high pH mobile phase reversed phase ultra high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B 927:112–123CrossRef Amundsen I, Øiestad ÅML, Ekeberg D, Kristoffersen L (2013) Quantitative determination of fifteen basic pharmaceuticals in ante- and post-mortem whole blood by high pH mobile phase reversed phase ultra high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B 927:112–123CrossRef
9.
go back to reference Yonezawa T, Asano T, Fujino T, Nishihara H (2013) Cyclodextrin-supported organic matrix for application of MALDI-MS for forensics. Soft-ionization to obtain protonated molecules of low molecular weight compounds. Chem Phys 419:17–22CrossRef Yonezawa T, Asano T, Fujino T, Nishihara H (2013) Cyclodextrin-supported organic matrix for application of MALDI-MS for forensics. Soft-ionization to obtain protonated molecules of low molecular weight compounds. Chem Phys 419:17–22CrossRef
10.
go back to reference Nozawa H, Minakata K, Yamagishi I, Hasegawa K, Wurita A, Gonmori K, Suzuki O, Watanabe K (2015) MALDI-TOF mass spectrometric determination of eight benzodiazepines with two of their metabolites in blood. Leg Med 17:150–156CrossRef Nozawa H, Minakata K, Yamagishi I, Hasegawa K, Wurita A, Gonmori K, Suzuki O, Watanabe K (2015) MALDI-TOF mass spectrometric determination of eight benzodiazepines with two of their metabolites in blood. Leg Med 17:150–156CrossRef
11.
go back to reference Guo Z, Zhang Q, Zou H, Guo B, Ni J (2003) A method for the analysis of low-mass molecules by MALDI-TOF mass spectrometry. Anal Chem 74:1637–1641CrossRef Guo Z, Zhang Q, Zou H, Guo B, Ni J (2003) A method for the analysis of low-mass molecules by MALDI-TOF mass spectrometry. Anal Chem 74:1637–1641CrossRef
13.
go back to reference Ulrich S, Isensee T, Pester U (1996) Simultaneous determination of amitriptyline, nortriptyline and four hydroxylated metabolites in serum by capillary gas-liquid chromatography with nitrogen-phosphorus-selective detection. J Chromatogr B 685:81–89CrossRef Ulrich S, Isensee T, Pester U (1996) Simultaneous determination of amitriptyline, nortriptyline and four hydroxylated metabolites in serum by capillary gas-liquid chromatography with nitrogen-phosphorus-selective detection. J Chromatogr B 685:81–89CrossRef
14.
go back to reference Broecker S, Pragst F, Bakdash A, Herre S, Tsokos M (2011) Combined use of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and high performance liquid chromatography with photodiode array detector (HPLC-DAD) in systematic toxicological analysis. Forensic Sci Int 212:215–226CrossRefPubMed Broecker S, Pragst F, Bakdash A, Herre S, Tsokos M (2011) Combined use of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and high performance liquid chromatography with photodiode array detector (HPLC-DAD) in systematic toxicological analysis. Forensic Sci Int 212:215–226CrossRefPubMed
15.
go back to reference Pelander A, Tyrkkö E, Ojanperä I (2009) In silico methods for predicting metabolism and mass fragmentation applied to quetiapine in liquid chromatography/time-of-flight mass spectrometry urine drug screening. Rapid Commun Mass Spectrom 23:506–514CrossRefPubMed Pelander A, Tyrkkö E, Ojanperä I (2009) In silico methods for predicting metabolism and mass fragmentation applied to quetiapine in liquid chromatography/time-of-flight mass spectrometry urine drug screening. Rapid Commun Mass Spectrom 23:506–514CrossRefPubMed
16.
go back to reference Davis PC, Bravo O, Gehrke M, Azumaya CT (2010) Development and validation of an LC-MS/MS method for the determination of quetiapine and four related metabolites in human plasma. J Pharm Biomed Anal 51:1113–1119CrossRefPubMed Davis PC, Bravo O, Gehrke M, Azumaya CT (2010) Development and validation of an LC-MS/MS method for the determination of quetiapine and four related metabolites in human plasma. J Pharm Biomed Anal 51:1113–1119CrossRefPubMed
17.
go back to reference Fisher DS, Handley SA, Taylor D, Flanagan RJ (2012) Measurement of quetiapine and four quetiapine metabolites in human plasma by LC-MS/MS. Biomed Chromatogr 26:1125–1132CrossRefPubMed Fisher DS, Handley SA, Taylor D, Flanagan RJ (2012) Measurement of quetiapine and four quetiapine metabolites in human plasma by LC-MS/MS. Biomed Chromatogr 26:1125–1132CrossRefPubMed
Metadata
Title
Simultaneous determination of cyclic antidepressants and their related drugs and the estimation of new metabolites in human whole blood and urine by MALDI-QTOF-mass spectrometry
Authors
Hideki Nozawa
Kayoko Minakata
Itaru Yamagishi
Koutaro Hasegawa
Masako Suzuki
Kunio Gonmori
Osamu Suzuki
Kanako Watanabe
Publication date
01-07-2016
Publisher
Springer Japan
Published in
Forensic Toxicology / Issue 2/2016
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-016-0313-1

Other articles of this Issue 2/2016

Forensic Toxicology 2/2016 Go to the issue