Quantitative Determination of Diphenhydramine and Orphenadrine in Human Serum by Capillary Gas Chromatography

Summary: Diphenhydramine has been in medical use for 35 years äs an antihistamine and hypnotic. We evaluated the pharmacokinetic parameters, which are not only important for disposition studies, in the serum of 10 volunteers who received a single dose of 31 mg diphenhydramine. For this purpose a suitable capillary GC-method was developed, which has a detection limit of 2 §/1 (serum); the calibration curve is linear between 2.5 and 120 g/l, the reproducibility is always better than 3.6 % and the average recovery is about 100.1%. The combination of a relatively nofi-polar extraction solvent, a selective detector (N-FID) and a fused silica, bonded-phase capillary column led to a more rapid sample clean-up procedure (no back-extraction needed) and is sensitive and specific enough for the quantitative determination of diphenhydramine, orphenadrine or other ethanolamines in human serum. Quantitative Bestimmung von Diphenhydramin und Orphenadrin im Serum des Menschen durch Kapillar-Gaschromatographi