HIGH-SENSITIVITY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY ELECTROSPRAY TANDEM MASS-SPECTROMETRY DETERMINATION OF TERFENADINE IN HUMAN PLASMA

A highly sensitive and selective HPLC-MS-MS method was developed for t he determination of terfenadine in human plasma. The analytes, terfena dine and terfenadine related compound A (internal standard), were extr acted from human plasma by methyl t-butyl ether/methylene chloride/n-b utyl chloride (3:2:1). The organic solvent is evaporated to dryness an d reconstituted in 100 mu L of acetonitrile/0.02 M ammonium acetate bu ffer pH 3.5 (50:50). Chromatographic separation is achieved on a TSK g et ODS-80(TS) column with a mobile phase composed of acetonitrike/1% f ormic acid/0.01. M ammonium acetate pH 4.0 (85:13:2). The analytes wer e detected by HPLC in conjunction with electrospray tandem mass spectr ometry. The assay was linear in the concentration ranges of 0.2 to 50 ng/mL. The analysis of pooled quality controls demonstrated excellent precision with relative standard deviations being less than 5.2%. The method is accurate with all intraday and over-all mean values being le ss than 5.3% from theoretical.