A simple liquid-liquid extraction with hexane for low-picogram determination of drugs and their metabolites in plasma by high-performance liquid chromatography with positive ion electrospray tandem mass spectrometry.

Autor: Xia YQ; Bioanalytical Research, Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 191, New Brunswick, NJ 08903-0191, USA., Whigan DB, Jemal M
Jazyk: angličtina
Zdroj: Rapid communications in mass spectrometry : RCM [Rapid Commun Mass Spectrom] 1999; Vol. 13 (15), pp. 1611-21.
DOI: 10.1002/(SICI)1097-0231(19990815)13:15<1611::AID-RCM683>3.0.CO;2-C
Abstrakt: Four sensitive, specific and accurate methods, based on high-performance liquid chromatography (HPLC) with positive ion electrospray tandem mass spectrometry (MS/MS) coupled with liquid-Liquid extraction (LLE), have been developed and validated for the low-picogram determination of two drug candidates and a metabolite (compounds I-III) in human, monkey and rat plasma. In the LLE procedure, hexane or a mixture of hexane and methyl t-butyl ether was used to isolate these compounds from plasma of the different species after basification of each biological sample with sodium carbonate. The reconstituted extracts were then injected into a positive ion electrospray LC/MS/MS system for the quantitative analysis. The lower limit of quantitation of the methods ranged from 20 to 200 pg/mL. The use of hexane for the LLE proved to be simple, rapid and reproducible, and provided very clean extracts with little interference. The inter- and intra-day precision for the four methods was within 9%, and the accuracy was in the range 94-107%. The effect of pH on the isomerization of I (E-isomer) to its Z-isomer (II) showed that the rate of isomerization increased with decrease in pH and that there was no isomerization at pH >/=6.
(Copyright 1999 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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