Determination of clemastine in human plasma by gas chromatography with nitrogen-phosphorus detection.

A method for the quantitative determination of clemastine in human plasma has been developed and validated. The assay uses gas chromatography with nitrogen-phosphorus detection and a HP-1 capillary column (25 mx0.22 mm, film thickness 0.33 mm) coated with dimethylpolysiloxane. Clemastine (with orphenadrine as internal standard) was isolated from human plasma using liquid-liquid extraction. A linear relationship was observed between 0.1 and 12.8 ng/ml using the peak area ratio of clemastine to orphenadrine with a correlation coefficient greater than 0.99 (the detection limit for clemastine was 0.06 ng/ml). The intra- and inter-day coefficients of variation were less than 11%. The developed method was used for the analysis of plasma samples from healthy volunteers (n = 19) to examine the pharmacokinetics of the antihistamine clemastine after single and multiple oral doses of clemastine fumarate.