Simultaneous microdetermination of biperiden, haloperidol, and trihexyphenidyl in plasma and its application to pharmacokinetic analysis after concomitant intravenous administration of the drugs to rabbits.

Abstract

A gas chromatographic method, using a moving precolumn sample injector and a nitrogenphosphorus detector, is presented for the simultancous quantitative analysis of biperiden, haloperidol and trihexyphenidyl in plasma. The drugs were extracted from 1 ml of plasma at pH 10.0 with ether, back-extracted into an acidic solution, and reextracted with ether after alkalinization. Diazepam was used as the internal reference standard. Processed standard curves of biperiden, haloperidol, and trihexyphenidyl plasma samples were linear over the concentration range of 1.25-50 ng/ml. Recoveries were found to be constant at various spiked doses, and the coefficients of variation were less than 11% for each drug. Plasma concentration-time courses after simultaneous administration of the three drugs to rabbits were analyzed by model-independent moment analysis. The volumes of distribution at the steady state per body weight of biperiden, haloperidol, and trihexyphenidyl were determined to be 18.5, 16.7, and 17.6 1/kg, respectively. Plasma clearances of the three drugs were 89.7, 61.7, and 79.9 ml/min/kg, respectively.