High-performance liquid chromatography-atmospheric pressure photoionization/tandem mass spectrometric analysis for small molecules in plasma

被引:75
作者
Hsieh, YS [1 ]
Merkle, K
Wang, GF
Brisson, JM
Korfmacher, WA
机构
[1] Schering Plough Res Inst, Drug Metab & Pharmacokinet Dept, Kenilworth, NJ 07033 USA
[2] Appl Biosyst Inc, Foster City, CA 94404 USA
关键词
D O I
10.1021/ac0300082
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A generic high-performance liquid chromatography (HPLC) system interfaced with an atmospheric pressure photoionization (APPI) source and a tandem mass spectrometer was developed for the quantitative determination of small molecules in plasma in support of exploratory in vivo pharmacokinetics. This report summarizes the effects of variations in reversed-phase mode HPLC conditions such as mobile-phase flow rate, solvent composition, organic modifier content, and nebulizer temperature on the photoionization efficiency of both clozapine and lonafarnib. The matrix ionization suppression effect on this method was investigated using the postcolumn infusion technique. The procedure was used to quantitate plasma levels following oral administration of 42 drug discovery compounds to rats. The pharmacokinetic results of 42 drug discovery compounds in rats evaluated by both APPI and atmospheric pressure chemical ionization interfaces were found to be well correlated.
引用
收藏
页码:3122 / 3127
页数:6
相关论文
共 19 条
  • [1] ALARY JF, 2002, P 50 ASMS C MASS SPE
  • [2] Bonfiglio R, 1999, RAPID COMMUN MASS SP, V13, P1175, DOI 10.1002/(SICI)1097-0231(19990630)13:12<1175::AID-RCM639>3.3.CO
  • [3] 2-S
  • [4] COX KA, 2001, AM PHARM REV, V4, P45
  • [5] HSIEH Y, IN PRESS J PHARM BIO
  • [6] Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma using fast-gradient liquid chromatography/tandem mass spectrometry
    Hsieh, YS
    Chintala, M
    Mei, H
    Agans, J
    Brisson, JM
    Ng, K
    Korfmacher, WA
    [J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2001, 15 (24) : 2481 - 2487
  • [7] Mechanistic investigation of ionization suppression in electrospray ionization
    King, R
    Bonfiglio, R
    Fernandez-Metzler, C
    Miller-Stein, C
    Olah, T
    [J]. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, 2000, 11 (11) : 942 - 950
  • [8] Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery
    Korfmacher, WA
    Cox, KA
    Ng, KJ
    Veals, J
    Hsieh, YS
    Wainhaus, S
    Broske, L
    Prelusky, D
    Nomeir, A
    White, RE
    [J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2001, 15 (05) : 335 - 340
  • [9] Liquid chromatography/mass spectrometry in anabolic steroid analysis-optimization and comparison of three ionization techniques: electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization
    Leinonen, A
    Kuuranne, T
    Kostiainen, R
    [J]. JOURNAL OF MASS SPECTROMETRY, 2002, 37 (07): : 693 - 698
  • [10] Liu M, 1998, CANCER RES, V58, P4947