The determination of biperiden in plasma using gas chromatography mass spectrometry: pharmacokinetics after intramuscular administration to guinea pigs†

A gas chromatographic–mass spectrometric (GC-MS) method has been developed for the analysis of the biperiden from plasma. The method utilizes 290 µl of plasma and a simple hexane extraction/clean-up procedure. Standard curves were linear over the range of 1.9–250 ng/mL. The range of correlation coefficients for the individual standard curves was 0.9984–0.9999; the largest coefficient of variation expressed as a percentage (%CV) was 11.5%. Precision and accuracy were examined by assessing between-day and within-day variability. For between-day precision, the %CVs ranged from 2.86 to 5.17%. Accuracy as expressed by percentage error ranging from −2.16 to 5.83%. The study for within-day precision demonstrated %CVs from 0.95 to 5.55% with accuracy from −3.37 to 2.45%. Applicability of the method was demonstrated by examining the pharmacokinetics of intramuscular (i.m.) biperiden as an anticonvulsant treatment in a guinea pig model for organophosphate (OP)-induced seizure activity. Mean pharmacokinetic parameter estimates were similar to literature values; selected mean pharmacokinetic parameter estimates were: apparent volume of distribution, 13.9 L/kg; half-life of elimination, 93 min; time to maximal plasma concentration, 27.4 min; and maximal plasma concentration, 32.22 ηg/mL. The time to maximal plasma concentration was found to be similar to the onset time for terminating OP-induced seizure activity in guinea pigs receiving biperiden as an anticonvulsant treatment. The studies indicate that the method affords the required precision, accuracy and sensitivity to assay biperiden at the doses utilized for these pharmacokinetic studies after i.m. administration to guinea pigs. Copyright © 2001 John Wiley & Sons, Ltd. Abbreviations used: AChE Acetylcholinesterase AUC area under the curve OP organophosphate 2-PAM pralidoxime chloride PYR pyridostigmine