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Quantitative analysis of the P‐glycoprotein inhibitor Elacridar (GF120918) in human and dog plasma using liquid chromatography with tandem mass spectrometric detection
Author(s) -
Stokvis Ellen,
Rosing Hilde,
Causon Roger C.,
Schellens Jan H.M.,
Beijnen Jos H.
Publication year - 2004
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.687
Subject(s) - chemistry , chromatography , selected reaction monitoring , electrospray , triple quadrupole mass spectrometer , liquid chromatography–mass spectrometry , extraction (chemistry) , tandem mass spectrometry , mass spectrometry , detection limit
A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method for the determination of the P‐glycoprotein and breast cancer resistance protein inhibitor Elacridar in human and dog plasma is described. The internal standard was stable isotopically labelled Elacridar. Sample pretreatment involved liquid–liquid extraction with tert ‐butyl methyl ether. Analysis of Elacridar and internal standard was performed by reversed‐phase LC on a basic stable minibore analytical column with an eluent consisting of acetonitrile and aqueous ammonia. An API‐2000 triple‐quadrupole mass spectrometer with an electrospray ion source was used in the positive‐ion multiple reaction monitoring mode. The run time per sample was only 6 min. The method is sensitive and specific, with a dynamic range from 1 to 500 ng ml −1 from 100 µl of human or dog plasma. The accuracy of the method was within 15% bias and the precision was lower than 15% for all tested concentration levels and in both matrices. The method is simple and the liquid–liquid extraction produces clean samples. This method was successfully applied to support the pharmacokinetics of a clinical trial in which orally applied Elacridar was used as a bioavailability enhancer. Copyright © 2004 John Wiley & Sons, Ltd.