Abstract
Due to the high prescription of antidepressants and their frequent involvement in clinical and forensic intoxications, reliable analytical techniques for identification and quantification of these therapeutic drugs should be available in clinical and toxicological laboratories. Improvements in liquid chromatography-mass spectrometry LC-MS(MS) technology over the last two decades have favored this technique to be one of the most commonly employed for this purpose, as it combines the high selectivity and sensitivity of the mass spectrometer with the great versatility of the liquid chromatographic separation. In this chapter, LC-MS(MS) applications for antidepressants determination are reviewed, detailing typical sample preparation techniques used for these therapeutic drugs, as well as common chromatographic and mass spectrometric characteristics. In addition, an LC-MS/MS method for the most common antidepressants used in clinical practice is described as an example of a whole method development and validation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Drasch G, Dahlmann F, von Meyer L et al (2008) Frequency of different anti-depressants associated with suicides and drug deaths. Int J Legal Med 122:115–121
Jonsson A, Holmgren P, Ahlner J (2004) Fatal intoxications in a Swedish forensic autopsy material during 1992–2002. Forensic Sci Int 143:53–59
Ohberg A, Vuori E, Klaukka T et al (1998) Antidepressants and suicide mortality. J Affect Disord 50:225–233
Shields LB, Hunsaker DM, Hunsaker JC III et al (2006) Toxicologic findings in suicide: a 10-year retrospective review of Kentucky medical examiner cases. Am J Forensic Med Pathol 27:106–112
Jones G, Singer P (2001) Miscellaneous prescription and over-the-counter medications. In: LeBeau M, Mozayani A (eds) Drug-facilitated sexual assault. A forensic handbook, 1st edn. Academic Press, San Diego, CA
Verster JC, Mets MA (2009) Psychoactive medication and traffic safety. Int J Environ Res Public Health 6:1041–1054
Brunnauer A, Laux G, Geiger E et al (2006) Antidepressants and driving ability: results from a clinical study. J Clin Psychiatry 67:1776–1781
Ramaekers JG (2003) Antidepressants and driver impairment: empirical evidence from a standard on-the-road test. J Clin Psychiatry 64:20–29
Walsh JM, Verstraete AG, Huestis MA et al (2008) Guidelines for research on drugged driving. Addiction 103:1258–1268
Mann K, Hiemke C, Schmidt LG et al (2006) Appropriateness of therapeutic drug monitoring for antidepressants in routine psychiatric inpatient care. Ther Drug Monit 28:83–88
Mitchell PB (2004) Therapeutic drug monitoring of non-tricyclic antidepressant drugs. Clin Chem Lab Med 42:1212–1218
Lundmark J, Bengtsson F, Nordin C et al (2000) Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients. Acta Psychiatr Scand 101:354–359
Burke MJ, Preskorn SH (1999) Therapeutic drug monitoring of antidepressants: cost implications and relevance to clinical practice. Clin Pharmacokinet 37:147–165
Hackett LP, Dusci LJ, Ilett KF (1998) A comparison of high-performance liquid chromatography and fluorescence polarization immunoassay for therapeutic drug monitoring of tricyclic antidepressants. Ther Drug Monit 20:30–34
Meenan GM, Barlotta S, Lehrer M (1990) Urinary tricyclic antidepressant screening: comparison of results obtained with Abbott FPIA reagents and Syva EIA reagents. J Anal Toxicol 14:273–276
Asselin WM, Leslie JM (1990) Use of the EMITtox serum tricyclic antidepressant assay for the analysis of urine samples. J Anal Toxicol 14:168–171
Banger M, Hermes B, Hartter S et al (1997) Monitoring serum concentrations of clomipramine and metabolites: fluorescence polarization immunoassay versus high performance liquid chromatography. Pharmacopsychiatry 30:128–132
Benitez J, Dahlqvist R, Gustafsson LL et al (1986) Clinical pharmacological evaluation of an assay kit for intoxications with tricyclic antidepressants. Ther Drug Monit 8:102–105
Yuan CM, Spandorfer PR, Miller SL et al (2003) Evaluation of tricyclic antidepressant false positivity in a pediatric case of cyproheptadine (periactin) overdose. Ther Drug Monit 25:299–304
Caravati EM, Juenke JM, Crouch BI et al (2005) Quetiapine cross-reactivity with plasma tricyclic antidepressant immunoassays. Ann Pharmacother 39:1446–1449
Maurer HH, Bickeboeller-Friedrich J (2000) Screening procedure for detection of antidepressants of the selective serotonin reuptake inhibitor type and their metabolites in urine as part of a modified systematic toxicological analysis procedure using gas chromatography-mass spectrometry. J Anal Toxicol 24:340–347
Lacassie E, Ragot S, Gaulier JM et al (1999) A specific dosage method for the analysis of 24 antidepressants using gas chromatography-mass spectrometry (GC/SM). Acta Clin Belg Suppl 1:20–24
Way BA, Stickle D, Mitchell ME et al (1998) Isotope dilution gas chromatographic-mass spectrometric measurement of tricyclic antidepressant drugs. Utility of the 4-carbethoxyhexafluorobutyryl derivatives of secondary amines. J Anal Toxicol 22:374–382
Salgado-Petinal C, Lamas JP, Garcia-Jares C et al (2005) Rapid screening of selective serotonin re-uptake inhibitors in urine samples using solid-phase microextraction gas chromatography-mass spectrometry. Anal Bioanal Chem 382:1351–1359
Eap CB, Bouchoux G, Amey M et al (1998) Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline, and their metabolites by gas chromatography-mass spectrometry. J Chromatogr Sci 36:365–371
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
Annesley TM (2003) Ion suppression in mass spectrometry. Clin Chem 49:1041–1044
Taylor PJ (2005) Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography-electrospray-tandem mass spectrometry. Clin Biochem 38:328–334
Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224
Thieme D, Rolf B, Sachs H et al (2008) Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms. Int J Legal Med 122:149–155
Smyth WF, Leslie JC, McClean S et al (2006) The characterisation of selected antidepressant drugs using electrospray ionisation with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry. Rapid Commun Mass Spectrom 20:1637–1642
Muller C, Vogt S, Goerke R et al (2000) Identification of selected psychopharmaceuticals and their metabolites in hair by LC/ESI-CID/MS and LC/MS/MS. Forensic Sci Int 113:415–421
Klys M, Scislowski M, Rojek S et al (2005) A fatal clomipramine intoxication case of a chronic alcoholic patient: application of postmortem hair analysis method of clomipramine and ethyl glucuronide using LC/APCI/MS. Leg Med (Tokyo) 7:319–325
de Castro A, Concheiro M, Quintela O et al (2008) LC-MS/MS method for the determination of nine antidepressants and some of their main metabolites in oral fluid and plasma. Study of correlation between venlafaxine concentrations in both matrices. J Pharm Biomed Anal 48:183–193
Coulter C, Taruc M, Tuyay J et al (2010) Antidepressant drugs in oral fluid using liquid chromatography-tandem mass spectrometry. J Anal Toxicol 34:64–72
Lobo ED, Loghin C, Knadler MP et al (2008) Pharmacokinetics of duloxetine in breast milk and plasma of healthy postpartum women. Clin Pharmacokinet 47:103–109
Goeringer KE, McIntyre IM, Drummer OH (2001) Postmortem tissue concentrations of venlafaxine. Forensic Sci Int 121:70–75
Avella J, Lehrer M, Katz M et al (2004) Two cases involving clomipramine intoxication. J Anal Toxicol 28:504–508
Gronewold A, Dettling A, Haffner HT et al (2009) Doxepin and nordoxepin concentrations in body fluids and tissues in doxepin associated deaths. Forensic Sci Int 190:74–79
Wenzel S, Aderjan R, Mattern R et al (2006) Tissue distribution of mirtazapine and desmethylmirtazapine in a case of mirtazapine poisoning. Forensic Sci Int 156:229–236
Society of Hair Testing (2004) Consensus on hair analysis. http://www.soht.org/. Accessed 2 Dec 2010
de Santana FJ, Bonato PS (2008) Enantioselective analysis of mirtazapine and its two major metabolites in human plasma by liquid chromatography-mass spectrometry after three-phase liquid-phase microextraction. Anal Chim Acta 606:80–91
Coles R, Kharasch ED (2007) Stereoselective analysis of bupropion and hydroxybupropion in human plasma and urine by LC/MS/MS. J Chromatogr B Anal Technol Biomed Life Sci 857:67–75
Petsalo A, Turpeinen M, Tolonen A (2007) Identification of bupropion urinary metabolites by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom 21:2547–2554
Segura M, Ortuno J, Farre M et al (2003) Quantitative determination of paroxetine and its 4-hydroxy-3-methoxy metabolite in plasma by high-performance liquid chromatography/electrospray ion trap mass spectrometry: application to pharmacokinetic studies. Rapid Commun Mass Spectrom 17:1455–1461
Jiang T, Rong Z, Peng L et al (2010) Simultaneous determination of citalopram and its metabolite in human plasma by LC-MS/MS applied to pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 878:615–619
Ma N, Zhang BK, Li HD et al (2007) Determination of duloxetine in human plasma via LC/MS and subsequent application to a pharmacokinetic study in healthy Chinese volunteers. Clin Chim Acta 380:100–105
Patel BN, Sharma N, Sanyal M et al (2008) Liquid chromatography tandem mass spectrometry assay for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in human plasma and its application to a bioequivalence study. J Pharm Biomed Anal 47:603–611
Rudberg I, Hermann M, Refsum H et al (2008) Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. Eur J Clin Pharmacol 64:1181–1188
Senthamil Selvan P, Gowda KV, Mandal U et al (2007) Determination of duloxetine in human plasma by liquid chromatography with atmospheric pressure ionization-tandem mass spectrometry and its application to pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 858:269–275
Yao M, Srinivas NR (2000) Simultaneous quantitation of d7-nefazodone, nefazodone, d7-hydroxynefazodone, hydroxynefazodone, m-chlorophenylpiperazine and triazole-dione in human plasma by liquid chromatographic-mass spectrometry. Biomed Chromatogr 14:106–112
Zhao RK, Cheng G, Tang J et al (2009) Pharmacokinetics of duloxetine hydrochloride enteric-coated tablets in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study. Clin Ther 31:1022–1036
Kirchherr H, Kuhn-Velten WN (2006) Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach. J Chromatogr B Anal Technol Biomed Life Sci 843:100–113
Dams R, Huestis MA, Lambert WE et al (2003) Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: influence of ionization type, sample preparation, and biofluid. J Am Soc Mass Spectrom 14:1290–1294
Bonfiglio R, King RC, Olah TV et al (1999) The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds. Rapid Commun Mass Spectrom 13:1175–1185
Naidong W, Bu H, Chen YL et al (2002) Simultaneous development of six LC-MS-MS methods for the determination of multiple analytes in human plasma. J Pharm Biomed Anal 28:1115–1126
Goeringer KE, McIntyre M, Drummer OH (2003) LC-MS analysis of serotonergic drugs. J Anal Toxicol 27:30–35
Zhang H, Heinig K, Henion J (2000) Atmospheric pressure ionization time-of-flight mass spectrometry coupled with fast liquid chromatography for quantitation and accurate mass measurement of five pharmaceutical drugs in human plasma. J Mass Spectrom 35:423–431
Remane D, Meyer MR, Peters FT et al (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
Titier K, Castaing N, Le-Deodic M et al (2007) Quantification of tricyclic antidepressants and monoamine oxidase inhibitors by high-performance liquid chromatography-tandem mass spectrometry in whole blood. J Anal Toxicol 31:200–207
Theron HB, van der Merwe MJ, Swart KJ et al (2007) Employing atmospheric pressure photoionization in liquid chromatography/tandem mass spectrometry to minimize ion suppression and matrix effects for the quantification of venlafaxine and O-desmethylvenlafaxine. Rapid Commun Mass Spectrom 21:1680–1686
Chen X, Duan X, Dai X et al (2006) Development and validation of a liquid chromatographic/tandem mass spectrometric method for the determination of sertraline in human plasma. Rapid Commun Mass Spectrom 20:2483–2489
Djordjevic S, Kovacevic I, Miljkovic B et al (2005) Liquid chromatographic-mass spectrometric method for the determination of fluoxetine and norfluoxetine in human plasma: application to clinical study. Farmaco 60:345–349
Liu W, Cai HL, Li HD (2007) High performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI) method for simultaneous determination of venlafaxine and its three metabolites in human plasma. J Chromatogr B Anal Technol Biomed Life Sci 850:405–411
Halvorsen TG, Pedersen-Bjergaard S, Reubsaet JLE et al (2003) Liquid-phase microextraction combined with liquid chromatography-mass spectrometry. Extraction from small volumes of biological samples. J Sep Sci 26:1520–1526
Juan H, Zhiling Z, Huande L (2005) Simultaneous determination of fluoxetine, citalopram, paroxetine, venlafaxine in plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). J Chromatogr B Anal Technol Biomed Life Sci 820:33–39
Bhatt J, Jangid A, Venkatesh G et al (2005) Liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for simultaneous determination of venlafaxine and its active metabolite O-desmethyl venlafaxine in human plasma. J Chromatogr B Anal Technol Biomed Life Sci 829:75–81
Jain DS, Sanyal M, Subbaiah G et al (2005) Rapid and sensitive method for the determination of sertraline in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). J Chromatogr B Anal Technol Biomed Life Sci 829:69–74
Shinozuka T, Terada M, Tanaka E (2006) Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method. Forensic Sci Int 162:108–112
Mercerolle M, Denooz R, Lachatre G et al (2008) A fatal case of bupropion (Zyban) overdose. J Anal Toxicol 32:192–196
Bhatt M, Shah S, Shivprakash (2010) Solid-phase extraction and analysis of paroxetine in human plasma by ultra performance liquid chromatography-electrospray ionization mass spectrometry. Biomed Chromatogr 24:209–215
De Castro A, Ramírez Fernandez MM, Laloup M, Samyn N, De Boeck G, Wood M, Maes V, López-Rivadulla M (2007) High-throughput on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry method for the simultaneous analysis of 14 antidepressants and their metabolites in plasma. J Chromatogr A 1160:3–12
Satonin DK, McCulloch JD, Kuo F et al (2007) Development and validation of a liquid chromatography-tandem mass spectrometric method for the determination of the major metabolites of duloxetine in human plasma. J Chromatogr B Anal Technol Biomed Life Sci 852:582–589
Kollroser M, Schober C (2002) Simultaneous determination of seven tricyclic antidepressant drugs in human plasma by direct-injection HPLC-APCI-MS-MS with an ion trap detector. Ther Drug Monit 24:537–544
Kollroser M, Schober C (2003) An on-line solid phase extraction liquid chromatography tandem mass spectrometry method for the analysis of citalopram, fluvoxamine and paroxetine in human plasma. Chromatographia 57:133–138
Sauvage FL, Gaulier JM, Lachatre G et al (2006) A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry technique for monitoring antidepressants in human serum. Ther Drug Monit 28:123–130
Santos-Neto AJ, Bergquist J, Lancas FM et al (2008) Simultaneous analysis of five antidepressant drugs using direct injection of biofluids in a capillary restricted-access media-liquid chromatography-tandem mass spectrometry system. J Chromatogr A 1189:514–522
Breaud AR, Harlan R, Di Bussolo JM et al (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 411:825–832
Queiroz ME, Oliveira EB, Breton F et al (2007) Immunoaffinity in-tube solid phase microextraction coupled with liquid chromatography-mass spectrometry for analysis of fluoxetine in serum samples. J Chromatogr A 1174:72–77
Alves C, Santos-Neto AJ, Fernandes C et al (2007) Analysis of tricyclic antidepressant drugs in plasma by means of solid-phase microextraction-liquid chromatography-mass spectrometry. J Mass Spectrom 42:1342–1347
Mao Y, Huang MQ, Xia YQ et al (2007) High-throughput quantitation of nefazodone and its metabolites in human plasma by high flow direct-injection LC-MS/MS. J Pharm Biomed Anal 43:1808–1819
Liu W, Wang F, Li HD (2007) Simultaneous stereoselective analysis of venlafaxine and O-desmethylvenlafaxine enantiomers in human plasma by HPLC-ESI/MS using a vancomycin chiral column. J Chromatogr B Anal Technol Biomed Life Sci 850:183–189
Patel BN, Sharma N, Sanyal M et al (2009) Analysis of second-generation antidepressant drug, sertraline and its active metabolite, N-desmethyl sertraline in human plasma by a sensitive and selective liquid chromatography-tandem mass spectrometry method. J Chromatogr B Anal Technol Biomed Life Sci 877:221–229
Patel BN, Sharma N, Sanyal M et al (2008) High throughput and sensitive determination of trazodone and its primary metabolite, m-chlorophenylpiperazine, in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 871:44–54
Naidong W, Eerkes A (2004) Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the analysis of paroxetine in human plasma. Biomed Chromatogr 18:28–36
Wei Z, Bing-Ren X, Cai-Yun W (2007) Liquid chromatography-mass spectrometry method for the determination of venlafaxine in human plasma and application to a pharmacokinetic study. Biomed Chromatogr 21:266–272
Choong E, Rudaz S, Kottelat A et al (2009) Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS. J Pharm Biomed Anal 50:1000–1008
Shen Z, Wang S, Bakhtiar R (2002) Enantiomeric separation and quantification of fluoxetine (Prozac) in human plasma by liquid chromatography/tandem mass spectrometry using liquid-liquid extraction in 96-well plate format. Rapid Commun Mass Spectrom 16:332–338
Rocha A, Marques MP, Coelho EB et al (2007) Enantioselective analysis of citalopram and demethylcitalopram in human and rat plasma by chiral LC-MS/MS: application to pharmacokinetics. Chirality 19:793–801
Arpino P, Baldwin MA, McLafferty FW (1974) Liquid chromatography-mass spectrometry. II. Continuous monitoring. Biomed Mass Spectrom 1:80–82
Niessen WMA (1999) History of LC-MS. In: Niessen WMA (ed) Liquid chromatography-mass spectrometry, 2nd edn. Marcel Dekker, Inc., New York
King R, Bonfiglio R, Fernandez-Metzler C et al (2000) Mechanistic investigation of ionization suppression in electrospray ionization. J Am Soc Mass Spectrom 11:942–950
Smeraglia J, Baldrey SF, Watson D (2001) Matrix effects and selectivity issues in LC-MS-MS. Chromatographia 55:S95–S99
Franceschi L, Faggiani A, Furlanut M (2009) A simple method to monitor serum concentrations of fluoxetine and its major metabolite for pharmacokinetic studies. J Pharm Biomed Anal 49:554–557
Saber AL (2009) On-line solid phase extraction coupled to capillary LC-ESI-MS for determination of fluoxetine in human blood plasma. Talanta 78:295–299
European Union Decision 2002/657/EC (17/8/2002) (2002) Off J Eur Commun 221:8–36
Peters FT (2006) Method validation using LC-MS. In: Polettini A (ed) Applications of LC-MS in toxicology, 1st edn. Pharmaceutical, London
Moraes MO, Lerner FE, Corso G et al (1999) Fluoxetine bioequivalence study: quantification of fluoxetine and norfluoxetine by liquid chromatography coupled to mass spectrometry. J Clin Pharmacol 39:1053–1061
Li C, Ji Z, Nan F et al (2002) Liquid chromatography/tandem mass spectrometry for the determination of fluoxetine and its main active metabolite norfluoxetine in human plasma with deuterated fluoxetine as internal standard. Rapid Commun Mass Spectrom 16:1844–1850
Sutherland FC, Badenhorst D, de Jager AD et al (2001) Sensitive liquid chromatographic-tandem mass spectrometric method for the determination of fluoxetine and its primary active metabolite norfluoxetine in human plasma. J Chromatogr A 914:45–51
Massaroti P, Cassiano NM, Duarte LF et al (2005) Validation of a selective method for determination of paroxetine in human plasma by LC-MS/MS. J Pharm Pharm Sci 8:340–347
Zhu Z, Neirinck L (2002) High-performance liquid chromatography-mass spectrometry method for the determination of paroxetine in human plasma. J Chromatogr B Anal Technol Biomed Life Sci 780:295–300
Qin F, Li N, Qin T et al (2010) Simultaneous quantification of venlafaxine and O-desmethylvenlafaxine in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 878:689–694
Rajasekhar D, Kumar IJ, Venkateswarlu P (2009) Rapid high-performance liquid chromatography-tandem mass spectrometry method for simultaneous measurement of venlafaxine and O-desmethylvenlafaxine in human plasma and its application in comparative bioavailability study. Biomed Chromatogr 23:1300–1307
Singh SS, Shah H, Gupta S et al (2004) Liquid chromatography-electrospray ionisation mass spectrometry method for the determination of escitalopram in human plasma and its application in bioequivalence study. J Chromatogr B Anal Technol Biomed Life Sci 811:209–215
Xu P, Li HD, Chen BM et al (2008) Determination of mianserin in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI/MS): application to a bioequivalence study in Chinese volunteers. J Pharm Biomed Anal 47:994–999
Chauhan B, Rani S, Guttikar S et al (2005) Analytical method development and validation of mianserin hydrochloride and its metabolite in human plasma by LC-MS. J Chromatogr B Anal Technol Biomed Life Sci 823:69–74
Gutteck U, Rentsch KM (2003) Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry. Clin Chem Lab Med 41:1571–1579
Castaing N, Titier K, Receveur-Daurel M et al (2007) Quantification of eight new antidepressants and five of their active metabolites in whole blood by high-performance liquid chromatography-tandem mass spectrometry. J Anal Toxicol 31:334–341
Fleishaker JC, Mucci M, Pellizzoni C et al (1999) Absolute bioavailability of reboxetine enantiomers and effect of gender on pharmacokinetics. Biopharm Drug Dispos 20:53–57
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
de Castro, A., Cruz, A., López-Rivadulla, M. (2012). Liquid Chromatography-Mass Spectrometry for the Determination of Antidepressants and Some of their Major Metabolites in Human Biological Matrices. In: Xu, Q., Madden, T. (eds) LC-MS in Drug Bioanalysis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-3828-1_7
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3828-1_7
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-3827-4
Online ISBN: 978-1-4614-3828-1
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)