Sensitive determination of paroxetine in canine plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS)

LC-MS/MS를 이용한 비글견 혈장 중 파록세틴의 고감도 분석

  • Chang, Kyu Young (Dept. of Drug Development Supporting Service. BioCore Co., Ltd.) ;
  • Kang, Seung Woo (Dept. of Drug Development Supporting Service. BioCore Co., Ltd.) ;
  • Han, Sang Beom (College of Pharmacy, Chung-Ang University) ;
  • Youm, Jeong-Rok (College of Pharmacy, Chung-Ang University) ;
  • Lee, Kyung Ryul (Dept. of Drug Development Supporting Service. BioCore Co., Ltd.) ;
  • Lee, Hee Joo (Dept. of Drug Development Supporting Service. BioCore Co., Ltd.)
  • 장규영 (바이오코아(주) 신약개발지원사업부) ;
  • 강승우 (바이오코아(주) 신약개발지원사업부) ;
  • 한상범 (중앙대학교 약학대학) ;
  • 염정록 (중앙대학교 약학대학) ;
  • 이경률 (바이오코아(주) 신약개발지원사업부) ;
  • 이희주 (바이오코아(주) 신약개발지원사업부)
  • Received : 2006.11.07
  • Accepted : 2007.02.27
  • Published : 2007.04.28

Abstract

A simple and sensitive method for the determination of paroxetine in canine plasma was developed and validated by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC-/MS/MS). Fluoxetine was used as an internal standard. Paroxetine and internal standard in plasma samples were extracted using TBME (tert-butyl methyl ether). A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 50% acetonitrile adjusted to pH 3 by formic acid. The reconstituted samples were injected into a Capcell Pak UG120 ($2.0{\times}150mm$, $5{\mu}m$) column. Using MS/MS with SRM (selective reaction monitoring) mode, the transitions (precursor to product) monitored were m/z $330{\rightarrow}192$ for paroxetine, and m/z $310{\rightarrow}148$ for internal standard. Linear detection responses were obtained for paroxetine concentration range of 0.02~5 ng/mL. A correlation coefficient of linear regression ($R^2$) was 0.9993. Detection of paroxetine in canine plasma was accurate and precise, with limit of quantification at 0.02 ng/mL. The method has been successfully applied to pharmacokinetic study of paroxetine in healthy beagle dogs.

Keywords

Paroxetine;LC-MS/MS;canine plasma;pharmacokinetic study

References

  1. R. Lane, D. Baldwin and S. Preskom, J. Psychopharmacol, 9, 5-11 (1995) https://doi.org/10.1097/00004850-199501005-00002
  2. B. Rodriguez de la Torre, J. Dreher, I. Malevany, M. Bagli, M. Kolbinger, H. Omran, B. Luderitz and M. L. Rao, Ther. Drug. Monit. 23, 435-440 (2001) https://doi.org/10.1097/00007691-200108000-00019
  3. M. Segura, J. Ortuno, M. Farre, R. Pacifici, S. Pichini, J. Joglar and J. Segura, Rapid Commun. Mass Spectrom., 17, 1455-1461 (2003) https://doi.org/10.1002/rcm.1067
  4. J. P. Foglia, D. Sorisio, M. Kirshner and B. G. Pollock, J. Chromatogr. B, 693, 147-151 (1997) https://doi.org/10.1016/S0378-4347(97)00010-8
  5. I. A. Zainaghi, V. L. Lanchote and R. H. C. Queiroz, Pharmacol. Res., 48, 217-221 (2003) https://doi.org/10.1016/S1043-6618(03)00098-7
  6. J. G. Shin, K. A. Kim, Y. R. Yoon, I. J. Cha, Y. H. Kim and S. G. Shin, J. Chromatogr. B, 713, 452-456 (1998) https://doi.org/10.1016/S0378-4347(98)00203-5
  7. W. Naidong and A. Eerkes, Biomed. Chromatogr., 18, 28-36 (2004) https://doi.org/10.1002/bmc.288
  8. K. Titier, N. Castaing, E. Scotto-Gomez, F. Pehourcq, N. Moore and M. Molimard, Ther. Drug. Monit, 25, 581-587 (2003) https://doi.org/10.1097/00007691-200310000-00007
  9. Z. Zhu and L. Neirinck, J Chromatogr. B Analyt Technol. Biomed. Life Sci., 780, 295-300 (2002) https://doi.org/10.1016/S1570-0232(02)00537-8
  10. C. Duverneuil, G. L. de la Grandmaison, P. de Mazancourt and J. C. Alvarez, Ther. Drug. Monit. 25, 565-573 (2003) https://doi.org/10.1097/00007691-200310000-00005
  11. H. J. Leis, W. Windischhofer and G. Fauler, J. Chromatogr. B, 779, 353-357 (2002) https://doi.org/10.1016/S1570-0232(02)00378-1
  12. P. Massaroti, N. M. Cassiano, L. F. Duarte, D.R. Campos, M. A. M. Marchioretto, G. Bernasconi, S. Calafatti, F. A. P. Barros, E. C. Meurer and J. Pedrazzoli, J. Pharm. Pharmaceut. Sci., 8, 340-347 (2005)
  13. C. G. Gottfries, I. Karlsson and A. L. Nyth, Int. Clin. Psychopharmacol, 6, 354-359 (1992)
  14. C. Lpez-Calull and N. Dominguez, J. Chromatogr. B, 724, 393-398 (1999) https://doi.org/10.1016/S0378-4347(98)00560-X
  15. Y. Zhang, D. K. Raap, F. Garcia, F. Serres, Q. Ma, G. Battaglia and L. D. Van de Kar, Brain Res, 855, 58-66 (2000) https://doi.org/10.1016/S0006-8993(99)02289-1
  16. C. T. Lai, E. S. Gorden, S. H. Kennedy, A. N. Bateson, R. T. Coutts and G. B. Baker, J. Chromatogr. B, 749, 275-279 (2000) https://doi.org/10.1016/S0378-4347(00)00389-3
  17. D. K. Raap and L. D. Van de Kar, Life Sci, 65, 1217-1235 (1999) https://doi.org/10.1016/S0024-3205(99)00169-1
  18. C. Hiemke and S. Hrtter, Pharmacol. and Ther., 85, 11-28 (2000) https://doi.org/10.1016/S0163-7258(99)00048-0
  19. H. Juan, Z. Zhiling and L. Huande, J. Chromatogr. B, 820, 33-39 (2005) https://doi.org/10.1016/j.jchromb.2005.03.006
  20. G. C. Dunbar, J. B. Cohn, L. F. Fabre, J. P. Feighner, R.R. Fieve, J. Mendels and R. K. Shrivastava, Br. J. Psychiatry, 159, 394-398 (1991) https://doi.org/10.1192/bjp.159.3.394
  21. S. M. Holliday and G. L. Plosker, Drugs Aging, 3 278- 299 (1993) https://doi.org/10.2165/00002512-199303030-00008