Skip to main content

Liquid Chromatography-Mass Spectrometry for the Determination of Antidepressants and Some of their Major Metabolites in Human Biological Matrices

  • Chapter
  • First Online:
LC-MS in Drug Bioanalysis

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. 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

    Google Scholar 

  2. Jonsson A, Holmgren P, Ahlner J (2004) Fatal intoxications in a Swedish forensic autopsy material during 1992–2002. Forensic Sci Int 143:53–59

    CAS  Google Scholar 

  3. Ohberg A, Vuori E, Klaukka T et al (1998) Antidepressants and suicide mortality. J Affect Disord 50:225–233

    CAS  Google Scholar 

  4. 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

    Google Scholar 

  5. 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

    Google Scholar 

  6. Verster JC, Mets MA (2009) Psychoactive medication and traffic safety. Int J Environ Res Public Health 6:1041–1054

    Google Scholar 

  7. Brunnauer A, Laux G, Geiger E et al (2006) Antidepressants and driving ability: results from a clinical study. J Clin Psychiatry 67:1776–1781

    CAS  Google Scholar 

  8. Ramaekers JG (2003) Antidepressants and driver impairment: empirical evidence from a standard on-the-road test. J Clin Psychiatry 64:20–29

    Google Scholar 

  9. Walsh JM, Verstraete AG, Huestis MA et al (2008) Guidelines for research on drugged driving. Addiction 103:1258–1268

    Google Scholar 

  10. 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

    Google Scholar 

  11. Mitchell PB (2004) Therapeutic drug monitoring of non-tricyclic antidepressant drugs. Clin Chem Lab Med 42:1212–1218

    CAS  Google Scholar 

  12. 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

    CAS  Google Scholar 

  13. Burke MJ, Preskorn SH (1999) Therapeutic drug monitoring of antidepressants: cost implications and relevance to clinical practice. Clin Pharmacokinet 37:147–165

    CAS  Google Scholar 

  14. 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

    CAS  Google Scholar 

  15. 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

    CAS  Google Scholar 

  16. 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

    CAS  Google Scholar 

  17. 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

    CAS  Google Scholar 

  18. 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

    CAS  Google Scholar 

  19. 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

    Google Scholar 

  20. Caravati EM, Juenke JM, Crouch BI et al (2005) Quetiapine cross-reactivity with plasma tricyclic antidepressant immunoassays. Ann Pharmacother 39:1446–1449

    CAS  Google Scholar 

  21. 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

    CAS  Google Scholar 

  22. 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

    CAS  Google Scholar 

  23. 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

    CAS  Google Scholar 

  24. 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

    CAS  Google Scholar 

  25. 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

    CAS  Google Scholar 

  26. 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

    CAS  Google Scholar 

  27. Annesley TM (2003) Ion suppression in mass spectrometry. Clin Chem 49:1041–1044

    CAS  Google Scholar 

  28. Taylor PJ (2005) Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography-electrospray-tandem mass spectrometry. Clin Biochem 38:328–334

    CAS  Google Scholar 

  29. Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224

    CAS  Google Scholar 

  30. 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

    Google Scholar 

  31. 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

    CAS  Google Scholar 

  32. 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

    CAS  Google Scholar 

  33. 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

    CAS  Google Scholar 

  34. 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

    Google Scholar 

  35. 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

    CAS  Google Scholar 

  36. 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

    CAS  Google Scholar 

  37. Goeringer KE, McIntyre IM, Drummer OH (2001) Postmortem tissue concentrations of venlafaxine. Forensic Sci Int 121:70–75

    CAS  Google Scholar 

  38. Avella J, Lehrer M, Katz M et al (2004) Two cases involving clomipramine intoxication. J Anal Toxicol 28:504–508

    CAS  Google Scholar 

  39. 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

    CAS  Google Scholar 

  40. 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

    CAS  Google Scholar 

  41. Society of Hair Testing (2004) Consensus on hair analysis. http://www.soht.org/. Accessed 2 Dec 2010

  42. 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

    Google Scholar 

  43. 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

    CAS  Google Scholar 

  44. Petsalo A, Turpeinen M, Tolonen A (2007) Identification of bupropion urinary metabolites by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom 21:2547–2554

    CAS  Google Scholar 

  45. 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

    CAS  Google Scholar 

  46. 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

    CAS  Google Scholar 

  47. 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

    CAS  Google Scholar 

  48. 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

    CAS  Google Scholar 

  49. 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

    CAS  Google Scholar 

  50. 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

    CAS  Google Scholar 

  51. 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

    CAS  Google Scholar 

  52. 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

    CAS  Google Scholar 

  53. 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

    CAS  Google Scholar 

  54. 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

    CAS  Google Scholar 

  55. 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

    CAS  Google Scholar 

  56. 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

    CAS  Google Scholar 

  57. Goeringer KE, McIntyre M, Drummer OH (2003) LC-MS analysis of serotonergic drugs. J Anal Toxicol 27:30–35

    CAS  Google Scholar 

  58. 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

    CAS  Google Scholar 

  59. 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

    CAS  Google Scholar 

  60. 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

    CAS  Google Scholar 

  61. 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

    CAS  Google Scholar 

  62. 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

    CAS  Google Scholar 

  63. 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

    CAS  Google Scholar 

  64. 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

    CAS  Google Scholar 

  65. 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

    CAS  Google Scholar 

  66. 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

    CAS  Google Scholar 

  67. 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

    CAS  Google Scholar 

  68. 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

    CAS  Google Scholar 

  69. 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

    CAS  Google Scholar 

  70. Mercerolle M, Denooz R, Lachatre G et al (2008) A fatal case of bupropion (Zyban) overdose. J Anal Toxicol 32:192–196

    CAS  Google Scholar 

  71. 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

    CAS  Google Scholar 

  72. 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

    Google Scholar 

  73. 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

    CAS  Google Scholar 

  74. 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

    CAS  Google Scholar 

  75. 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

    CAS  Google Scholar 

  76. 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

    CAS  Google Scholar 

  77. 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

    CAS  Google Scholar 

  78. 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

    CAS  Google Scholar 

  79. 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

    CAS  Google Scholar 

  80. 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

    CAS  Google Scholar 

  81. 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

    CAS  Google Scholar 

  82. 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

    CAS  Google Scholar 

  83. 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

    CAS  Google Scholar 

  84. 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

    CAS  Google Scholar 

  85. 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

    CAS  Google Scholar 

  86. 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

    CAS  Google Scholar 

  87. 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

    CAS  Google Scholar 

  88. 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

    CAS  Google Scholar 

  89. 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

    CAS  Google Scholar 

  90. Arpino P, Baldwin MA, McLafferty FW (1974) Liquid chromatography-mass spectrometry. II. Continuous monitoring. Biomed Mass Spectrom 1:80–82

    CAS  Google Scholar 

  91. Niessen WMA (1999) History of LC-MS. In: Niessen WMA (ed) Liquid chromatography-mass spectrometry, 2nd edn. Marcel Dekker, Inc., New York

    Google Scholar 

  92. 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

    CAS  Google Scholar 

  93. Smeraglia J, Baldrey SF, Watson D (2001) Matrix effects and selectivity issues in LC-MS-MS. Chromatographia 55:S95–S99

    Google Scholar 

  94. 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

    CAS  Google Scholar 

  95. 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

    CAS  Google Scholar 

  96. European Union Decision 2002/657/EC (17/8/2002) (2002) Off J Eur Commun 221:8–36

    Google Scholar 

  97. Peters FT (2006) Method validation using LC-MS. In: Polettini A (ed) Applications of LC-MS in toxicology, 1st edn. Pharmaceutical, London

    Google Scholar 

  98. 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

    CAS  Google Scholar 

  99. 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

    CAS  Google Scholar 

  100. 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

    CAS  Google Scholar 

  101. 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

    CAS  Google Scholar 

  102. 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

    CAS  Google Scholar 

  103. 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

    CAS  Google Scholar 

  104. 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

    CAS  Google Scholar 

  105. 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

    CAS  Google Scholar 

  106. 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

    CAS  Google Scholar 

  107. 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

    CAS  Google Scholar 

  108. 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

    CAS  Google Scholar 

  109. 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

    CAS  Google Scholar 

  110. 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

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manuel López-Rivadulla .

Editor information

Editors and Affiliations

Rights and permissions

Reprints 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

Publish with us

Policies and ethics