Simultaneous analysis of losartan, its active metabolite, and hydrochlorothiazide in human plasma by a UPLC-MS/MS method

Authors : Priyanka A SHAH, Primal SHARMA, Jaivik V SHAH, Mallika SANYAL, Pranav S SHRIVASTAV

Pages : 714-733

Doi:10.3906/kim-1502-4

View : 17 | Download : 13

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :A selective and sensitive ultra performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of losartan insert ignore into journalissuearticles values(LOS);, EXP-3174, which is an active metabolite LOS carboxylic acid, and hydrochlorothiazide insert ignore into journalissuearticles values(HCTZ); in human plasma. Solid-phase extraction was carried out on Oasis HLB cartridges with 100 $\mu $L of plasma to give an extraction recovery in the range of 88.5%-102.5% for the three analytes. Chromatography on a BEH C18 column afforded baseline separation of all the analytes within 2.4 min using 1.0% formic acid in water and acetonitrile insert ignore into journalissuearticles values(15:85, v/v); as the mobile phase. Quantitation was performed with multiple reaction monitoring in the negative ionization mode. The response of the method was linear over a dynamic range of 0.5-500, 1.0-750, and 0.25-150 ng/mL for LOS, EXP-3174, and HCTZ, respectively. Extent of signal suppression/enhancement was examined through postcolumn infusion. The effect of matrix components was evaluated by postextraction spiking and calculation of the slope of calibration lines. The method was successfully applied to a bioequivalence study of 50 mg losartan and 12.5 mg hydrochlorothiazide tablet formulation in 65 healthy human subjects. Reproducibility of the method was shown by reanalysis of 213 incurred samples.
Keywords : Losartan, EXP 3174, hydrochlorothiazide, solid phase extraction, UPLC MS MS, human plasma