DETERMINATION OF PRAMIPEXOLE (U-98,528) IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION TANDEM MASS-SPECTROMETRY

A highly sensitive and selective HPLC-MS-MS method was developed for t he determination of pramipexole in human plasma. The analytes, pramipe xole and BHT-920 (internal standard), were extracted from plasma at ba sic pH with methyl tert.-butyl ether (MTBE). MTBE was evaporated to dr yness and reconstituted in 100 mu l of (95:5) methanol-water. Chromato graphic separation was achieved on a Zorbax SB-CN column with a mobile phase of (15:5:80) water-0.1 M ammonium acetate-methanol. The analyte s were detected utilizing HPLC in conjunction with atmospheric pressur e chemical ionization (APCI) tandem mass spectrometry (MS-MS). The ass ay was linear in the concentration ranges of 50 to 5000 pg/ml. The ana lysis of pooled quality controls (150, 750, and 3000 pg/ml) demonstrat ed excellent precision with relative standard deviations (R.S.D.) (n=1 8) of 7.2%, 5.3% and 5.2%, respectively. The method is accurate with a ll intra-day (n=6) and overall (n=18) mean values being less than 11.7 % from theoretical.