The simultaneous determination of diazepam and its three metabolites in dog plasma by high-performance liquid chromatography with mass spectroscopy detection

被引:33
作者
Liu, Z
Short, J
Rose, A
Ren, S
Contel, N
Grossman, S
Unger, S
机构
[1] DuPont Pharmaceut Co, Stine Haskell Res Ctr, Dept Drug Metab & Pharmacokinet, Newark, DE 19714 USA
[2] TAP Pharmaceut Prod, Lake Forest, IL 60045 USA
关键词
HPLC methods; electrospray ionization; MS/MS detection; dog plasma; automated SPE;
D O I
10.1016/S0731-7085(01)00404-6
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A fast, sensitive and specific LC/MS/MS method for the simultaneous determination of diazepam and its three metabolites, oxazepam, temazepam and desmethyldiazepam. in dog plasma is described. The method consists of an automated 96-well solid phase extraction procedure and electrospray LC/MS/MS analysis. D-5-Diazepam is used as the internal standard for all the compounds. Intra-day and inter-day assay coefficients of variations are less than 12.7%. The lower limit of quantitation (LLOQ) is 1 nM for each analyte, based on 0.1 ml aliquots of dog plasma. The analytical run time was 5 min, Linearity is observed over the range of 1-500 nM. This method has been used to support the discovery of pharmacokinetic studies. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:321 / 330
页数:10
相关论文
共 13 条
[1]   DETERMINATION OF 1,4-BENZODIAZEPINES AND 1,4-BENZODIAZEPINE-2-ONES IN BLOOD BY ELECTRON-CAPTURE GAS-LIQUID-CHROMATOGRAPHY [J].
DESILVA, JAF ;
BEKERSKY, I ;
PUGLISI, CV ;
BROOKS, MA ;
WEINFELD, RE .
ANALYTICAL CHEMISTRY, 1976, 48 (01) :10-19
[2]   ENTRY OF DIAZEPAM AND ITS MAJOR METABOLITE INTO CEREBROSPINAL-FLUID [J].
GREENBLATT, DJ ;
OCHS, HR ;
LLOYD, BL .
PSYCHOPHARMACOLOGY, 1980, 70 (01) :89-93
[3]  
HOHNE D, 1987, ANAL CHEM, V328, P99
[4]  
JONES CE, 1989, CLIN CHEM, V35, P1394
[5]   Determination of 1,4-benzodiazepines by high-performance liquid chromatography electrospray tandem mass spectrometry [J].
Kleinschnitz, M ;
Herderich, M ;
Schreier, P .
JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS, 1996, 676 (01) :61-67
[6]  
LOSCHER W, 1981, ARCH INT PHARMACOD T, V254, P180
[7]  
MAHJOUB AE, 2000, J CHROMATOGR B, V742, P381
[8]  
McClean S, 2000, ELECTROPHORESIS, V21, P1381, DOI 10.1002/(SICI)1522-2683(20000401)21:7<1381::AID-ELPS1381>3.0.CO
[9]  
2-1
[10]   Determination of 1,4-benzodiazepines and their metabolites by capillary electrophoresis and high-performance liquid chromatography using ultraviolet and electrospray ionisation mass spectrometry [J].
McClean, S ;
O'Kane, E ;
Hillis, J ;
Smyth, WF .
JOURNAL OF CHROMATOGRAPHY A, 1999, 838 (1-2) :273-291