Journal
CHROMATOGRAPHIA
Volume 69, Issue 9-10, Pages 843-852Publisher
SPRINGER HEIDELBERG
DOI: 10.1365/s10337-009-1017-z
Keywords
Column liquid chromatography; Tandom mass spectrometry; Protein binding drug-drug interaction; Benazepril, gliclazide and valsartan; Rhein
Funding
- National 863'' Project [2003A A2Z347A, 2005AA2Z3C70, 2002AA 2Z3113]
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For new drug candidates with high protein binding in the treatment of diabetic nephropathy, their influence on the protein bindings of angiotensin-converting enzyme inhibitors, sulfonylurea drugs, and angiotensin receptor blockers should be predicted to prevent side effects. To provide an efficient tool for this study, a sensitive and rapid LC-MS-MS method was developed for the simultaneous quantification of representative drugs, benazepril, gliclazide and valsartan in human plasma. Chromatographic separation was performed on a Shim-pack VP-ODS C18 column (250 x 2.0 mm i.d., 5 mu m) using methanol-0.05% formic acid (90:10, v/v) as mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source and operated in SRM mode. Lower limits of quantification were 2, 2 and 20 ng(-1) mL for benazepril, gliclazide and valsartan with 0.1 mL plasma sample. The method fulfills the precision, accuracy, linearity, sensitivity, selectivity requirements to quantify the three drugs and has been successfully used to studying protein binding of benazepril, gliclazide and valsartan in the presence of rhein.
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