An automated method for the simultaneous determination of pravastatin, 3-hydroxy isomeric metabolite, pravalactone and fenofibric acid in human plasma by sensitive liquid chromatography combined with diode array and tandem mass spectrometry detection

被引:21
作者
Mertens, B. [1 ]
Cahay, B. [1 ]
Klinkenberg, R. [1 ]
Streel, B. [1 ]
机构
[1] Bioanalyt Dept, B-6900 Marche En Famenne, Belgium
关键词
pravastatin; 3-hydroxy isomeric metabolite; pravalactone; fenofibric acid; LC-DAD-MS/MS; pharmacokinetics; solid-phase extraction; validation;
D O I
10.1016/j.chroma.2008.01.060
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
In this study, a sensitive and selective method based on liquid chromatography combined with diode array and tandem mass spectrometry detection (LC-DAD-MS/MS) was developed for the simultaneous quantitative determination of fenofibric acid, pravastatin and its main metabolites in human plasma. In this method, an automated solid-phase extraction (SPE) on disposable extraction cartridges (DECs) is used to isolate the compounds from the biological matrix and to prepare a cleaner sample before injection and analysis in the LC-DAD-MS/MS system. On-line LC-DAD-MS/MS system using an atmospheric pressure ionization (TurboIonSpray) was then developed for the simultaneous determination of pravastatin, 3-hydroxy isomeric metabolite (3-OH metab), pravalactone and fenofibric acid. The separation is obtained on an endcapped dodecyl silica based stationary phase using a mobile phase consisting of a mixture of acetonitrile, methanol and 5 mM ammonium acetate solution (30:30:40, v/v/v). Sulindac and triamcinolone were used as internal standards (ISs). The detection of the fenofibric acid and sulindac was achieved by means of a DAD system. The MS/MS ion transitions monitored were m/z 442.2 -> 269.1, 442.2 -> 269.1, 424.3 -> 183.0 and 435.2 -> 397.2 for pravastatin, 3-OH metab, pravalactone and triamcinolone, respectively. The method was validated regarding stability, selectivity, extraction efficiency, response function, trueness, precision lower limit of quantitation and matrix effect. The limits of quantitation (LOQs) were around 0.50 ng/ml for pravastatin, 0.25 ng/ml for 3-OH metab, 0.05 ng/ml for pravalactone and 0.25 mu g/ml for fenofibric acid. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:493 / 502
页数:10
相关论文
共 42 条
[11]  
ELSSOM LF, 1976, J CHROMATOGR, V123, P463
[12]  
*EUR PHARM, MON
[13]  
FRANCOISDAINVIL.E, 1982, J PHARM CLIN, V1, P215
[14]   DETERMINATION OF PRAVASTATIN SODIUM AND ITS MAJOR METABOLITES IN HUMAN-SERUM PLASMA BY CAPILLARY GAS-CHROMATOGRAPHY NEGATIVE-ION CHEMICAL IONIZATION MASS-SPECTROMETRY [J].
FUNKE, PT ;
IVASHKIV, E ;
ARNOLD, ME ;
COHEN, AI .
BIOMEDICAL AND ENVIRONMENTAL MASS SPECTROMETRY, 1989, 18 (10) :904-909
[15]   A COMPARISON OF THE BIOAVAILABILITY OF STANDARD OR MICRONIZED FORMULATIONS OF FENOFIBRATE [J].
GUICHARD, JP ;
SAURON, RLP .
CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL, 1993, 54 (05) :610-614
[16]   The SFSTP guide on the validation of chromatographic methods for drug bioanalysis: from the Washington Conference to the laboratory [J].
Hubert, P ;
Chiap, P ;
Crommen, J ;
Boulanger, B ;
Chapuzet, E ;
Mercier, N ;
Bervoas-Martin, S ;
Chevalier, P ;
Grandjean, D ;
Lagorce, P ;
Lallier, M ;
Laparra, MC ;
Laurentie, M ;
Nivet, JC .
ANALYTICA CHIMICA ACTA, 1999, 391 (02) :135-148
[17]  
Hubert P., 2003, STP Pharma Prat Tech Reglementations, V13, P101
[18]   HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY DETERMINATION OF PRAVASTATIN IN PLASMA [J].
IACONA, I ;
REGAZZI, MB ;
BUGGIA, I ;
VILLANI, P ;
FIORITO, V ;
MOLINARO, M ;
GUARNONE, E .
THERAPEUTIC DRUG MONITORING, 1994, 16 (02) :191-195
[19]  
Kawabata K, 1998, BIOMED CHROMATOGR, V12, P271, DOI 10.1002/(SICI)1099-0801(199809/10)12:5<271::AID-BMC746>3.3.CO
[20]  
2-6