Abstract
Clozapine is indicated for the treatment of schizophrenia and related psychotic disorders. Several methods have been developed for monitoring Clozapine levels; however, they possess limited specificity and are often laborious. This study describes a simple liquid chromatography/tandem mass spectrometer (LCMS) method in human serum. The ion transitions monitored were m/z 327, 270, 296 for Clozapine, m/z 313, 192, 227 for Norclozapine and m/z 328, 271 for Loxapine. The assay is linear (25–1000 ng/ml) and showed a good correlation (r=0.98) within the analytical range of 79–1210 ng/ml in human serum. This assay is highly specific and sensitive for the simultaneous measurements of Clozapine and Norclozapine. The simplification of this assay makes it ideal for high throughput analyses of the patient samples in a routine clinical laboratory staffed with general medical technologists. J. Clin. Lab. Anal. 23:394–398, 2009. © 2009 Wiley‐Liss, Inc.
Keywords: Clozapine, Norclozapine, LCMS
REFERENCES
- 1. Polsky D, Doshi JA, Bauer MS, Glick HA. Am J Psychiatry 2006;163:2047. [DOI] [PubMed] [Google Scholar]
- 2. Kane J, Honigfeld G, Singer J, Meltzer H. Arch Gen Psychiatry 1988;45:789. [DOI] [PubMed] [Google Scholar]
- 3. Heipertz R, Pilz H, Beckers W. Arch Toxicol 1977;37:313. [DOI] [PubMed] [Google Scholar]
- 4. Richter K. J Chromatogr 1988;434:465. [DOI] [PubMed] [Google Scholar]
- 5. Jennison TA, Brown P, Crossett J, Kushnir M, Urry FM. J Anal Toxicol 1995;19:537. [DOI] [PubMed] [Google Scholar]
- 6. Bondesson U, Lindstrom LH. Psychopharmacology (Berl) 188;95:472. [DOI] [PubMed] [Google Scholar]
- 7. Zhu R, Wang C, Zhao J, Chen Y, Zhou H. SEPU 1998;16:317. [PubMed] [Google Scholar]
- 8. Melent'ev AB, Kurochkina IV. Sud Med Ekspert 1999;42:27. [PubMed] [Google Scholar]
- 9. Palego L, Dell'Osso L, Marazziti D, et al. Prog Neuropsychopharmacol Biol Psychiatry 2001;25:519. [DOI] [PubMed] [Google Scholar]
- 10. Haring C, Humpel C, Auer B, et al. J Chromatogr 1988;428:160. [DOI] [PubMed] [Google Scholar]
- 11. Humpel C, Haring C, Saria A. J Chromatogr 1989;491:235. [DOI] [PubMed] [Google Scholar]
- 12. Lovdahl MJ, Perry PJ, Miller DD. Ther Drug Monit 1991;13:69. [DOI] [PubMed] [Google Scholar]
- 13. Weigmann H, Hiemke C. J Chromatogr 1992;583:209. [DOI] [PubMed] [Google Scholar]
- 14. Chung MC, Lin SK, Chang WH, Jann MW. J Chromatogr 1993;613:168. [DOI] [PubMed] [Google Scholar]
- 15. Gupta RN. J Chromatogr B Biomed Appl 1955;673:311. [DOI] [PubMed] [Google Scholar]
- 16. McCarthy PT, Hughes S, Paton C. Biomed Chromatogr 1995;9:36. [DOI] [PubMed] [Google Scholar]
- 17. Olesen OV, Poulsen B. J Chromatogr 1993;622:39. [DOI] [PubMed] [Google Scholar]
- 18. Freeman DJ, Li MC, Oyewumi K. Ther Drug Monit 1996;18:688. [DOI] [PubMed] [Google Scholar]
- 19. Akerman KK. J Chromatogr B Biomed Sci Appl 1997;696:253. [PubMed] [Google Scholar]
- 20. Edno L, Combourieu I, Cazenave M, Tignol J. J Pharm Biomed Anal 1997;16:311. [DOI] [PubMed] [Google Scholar]
- 21. Guitton C, Kinowski JM, Aznar R, Bressolle F. J Chromatogr B Biomed Sci Appl 1997;690:211. [DOI] [PubMed] [Google Scholar]
- 22. Weigmann H, Bierbrauer J, Hartter S, Hiemke C. Ther Drug Monit 1997;19:480. [DOI] [PubMed] [Google Scholar]
- 23. Avenoso A, Facciola G, Campo GM, Fazio A, Spina E. J Chromatogr B Biomed Sci Appl 1998;714:299. [DOI] [PubMed] [Google Scholar]
- 24. Llerena A, Berecz R, Norberto MJ, de la Rubia A. J Chromatogr B Biomed Sci Appl 2001;755:349. [DOI] [PubMed] [Google Scholar]
- 25. Liu YY, van Troostwijk LJ, Guchelaar HJ. Biomed Chromatogr 2001;15:280. [DOI] [PubMed] [Google Scholar]
- 26. Weigmann H, Hartter S, Maehrlein S, et al. J Chromatogr B Biomed Sci Appl 2001;759:63. [DOI] [PubMed] [Google Scholar]
- 27. Waschgler R, Hubmann MR, Conca A, Moll W, Konig P. Int J Clin Pharmacol Ther 2002;40:554. [DOI] [PubMed] [Google Scholar]
- 28. Rosland M, Szeto P, Procyshyn R, Barr AM, Wasan KM. Drug Dev Ind Pharm 2007;33:1158. [DOI] [PubMed] [Google Scholar]
- 29. Mercolini L, Bugamelli F, Kenndler E, Boncompagni G, Franchini L, Raggi MA. J Chromatogr B Analyt Technol Biomed Life Sci 2007;846:273. [DOI] [PubMed] [Google Scholar]
- 30. Aravagiri M, Marder SR. J Pharm Biomed Anal 2001;26:301. [DOI] [PubMed] [Google Scholar]
- 31. Kollroser M, Schober C. Rapid Commun Mass Spectrom 2002;16:1266. [DOI] [PubMed] [Google Scholar]
- 32. Niederlander HA, Koster EH, Hilhorst MJ, et al. J Chromatogr B Analyt Technol Biomed Life Sci 2006;834:98. [DOI] [PubMed] [Google Scholar]
- 33. Israili ZH, Dayton PG. Drug Metab Rev 2001;33:161. [DOI] [PubMed] [Google Scholar]
- 34. Flanagan RJ, Amin A, Seinen W. Forensic Sci Int 2003;132:9. [DOI] [PubMed] [Google Scholar]
- 35. Oyewumi LK, Cernovsky ZZ, Freeman DJ, Streiner DL. Can J Psychiatry 2002;47:257. [DOI] [PubMed] [Google Scholar]
- 36. Welch J, Manschreck T, Redmond D. J Neuropsychiatry Clin Neurosci 1994;6:250. [DOI] [PubMed] [Google Scholar]
- 37. Risby ED, Epstein CM, Jewart RD, et al. J Neuropsychiatry Clin Neurosci 1995;7:466. [DOI] [PubMed] [Google Scholar]
