LC-MS/MS method using unbonded silica column and aqueous/methanol mobile phase for the simultaneous quantification of a drug candidate and co-administered metformin in rat plasma

BMS-754807 and metformin were co-administered in drug discovery studies which required the quantitation of both compounds in plasma Since the two compounds are chemically and Si maul ally dissimilar, developing a single bioanalytical method presented a number of chromatographic challenges including the achievement of appropriate retention times and peak shapes on a single analytical column To address this chromatographic challenge, we investigated different LC columns under different gradient elution schemes using aqueous/organic mobile phases Using unbonded silica column and aqueous/methanol mobile phase, we were able to obtain robust and well-resolving chromatographic conditions to support the development and implementation of a single LC-MS/MS bioanalytical method The use of sub-2 micron particle sizes and a high flow rate, which are attainable with UPLC systems, enhanced the method The method performance evaluation showed that the method easily met the normally used acceptance cruel la for bioanalytical methods, namely a deviation of +/- 15% from the nominal concentration except. at lower limit of quantitation (LLOQ), where +/- 20% is accepted The repot red LLOQ of 7 8 ng/ml, for both BMS-754807 and metformin, was adequate to support the pharmacokinetic studies (C) 2010 Elsevier BV All rights reserved.