Sensitive, Selective and Rapid Determination of Lafutidine in Human Plasma by Solid Phase Extraction - Liquid Chromatography-Tandem Mass Spectrometry

摘要

A simple, sensitive and high throughput liquid chromatography-tandem mass spectrometry method has been developed for the determination of lafutidine in human plasma. Sample clean-up involved solid phase extraction of lafutidine along with ranitidine as the internal standard from 100 μL of human plasma. The chromatographic separation is achieved within 2.5 min on a Grace Denali C18 (50 × 4.6 mm,5 μ) column using 2 mM ammonium acetate, pH 3.0 adjusted with acetic acid and acetonitrile (20: 80, v/v) as the mobile phase. The precursor → product ion transitions for lafutidine (m/z 432.2 → 351.4) and IS (m/z 315.3 → 176.3) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and positive ion mode. The method is validated over a wide dynamic concentration range of 0.25-1000 ng/mL. The mean relative recovery for lafutidine across quality controls is 97.9%. The relative matrix effect between eight different plasma lots, expressed as coefficient of variation of the slopes of the calibration lines is 1.94. The method is applied to a bioequivalence study of 10 mg lafutidine tablet formulation in 26 healthy Indian male subjects under fasting condition. The reproducibility of study data is demonstrated by analysis of 93 incurred samples.