Determination of Losartan in Human Plasma by Liquid Chromatography Electrospray Ionization Mass Spectrometry (LC-ESI-MS): Application to Bioequivalence Study

Abstract

A sensitive, simple, rapid, and specific liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) method was developed and validated for the identification and quantification of losartan in a small volume of human plasma. Losartan and I.S. were successfully separated on a CN column with a mobile phase of acetonitrile-0.2% formic acid solution (68:32, v/v). Detection was performed on a single quadrupole mass spectrometer by a selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The ESI source was set at positive ionization mode. The ion signal of m/z 422.79 and 194.81 were measured for losartan and I.S., respectively. The limit of detection (LOD) was 0.5 ng/mL (signal-to-noise ratio of 10.03) using only 200 μL of human plasma samples. The calibration curve was an excellent linear fit over the range of concentrations 1.0–1000 ng/mL (R2 = 0.9987) of losartan in human plasma. Consequently, all of our results fulfilled the common standard criteria of bioequivalence, 0.80 to 1.25 by the Korean and US Food and Drug Administration. In addition to the confidence intervals (C.I.) 90% of the pharmaceutical parameters, a two-way ANOVA showed no significant difference between the two formulations. This method was successfully applied to bioequivalence study of two brands of losartan potassium tablet (100 mg) formulations after a single oral administration.