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

Abstract

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-GaschromatographieZusammenfassung: Diphenhydramin findet seit über 35 Jahren als Antihistaminicum und Hypnoticum medizinische Verwendung. Wir bestimmten die nicht nur für pharmakologische Studien wichtigen pharmakokinetischen Kenngrößen im Serum von 10 Probanden nach Gabe einer Einzeldosis von 31 mg Diphenhydramin.Hierzu entwickelten wir eine geeignete kapillar-gaschroinatographische Methode mit einer Nachweisgrenze von 2 ^g/l Serum; die Kalibrierungskurve ist linear zwischen 2,5 und 120 g/l, die Wiederholbarkeit immer besser als 3,6% und die Wiederfindungsrate lag bei 100,1%.Die Kombination eines relativ unpolaren Lösungsmittels zur Extraktion mit einem selektiven Detektor (N-FID) und einer fused-silica, bonded phase-Kapillare führt, da keine Rückextraktion benötigt wird, zu kürze-ren Proberiaufbefeitungszeiten und ist empfindlich und spezifisch genug für die quantitative Bestimmung von Diphenhydramin, Orphenadrin und anderen Ethanolaminen im menschlichen Serum.

Acute Inhibition of the Human Kv1.5 Channel by H₁ Receptor Antagonist Dimenhydrinate: Mode of Action

“…18) Moreover, when 50 mg of diphenhydramine-the appropriate adult oral dose-was orally administered, peak plasma concentrations were 80-100 ng/mL corresponding to 1.1-1.4 µM dimenhydrinate. 19,20) The lethal serum concentration of diphenhydramine has been defined as 5 µg/mL, which corresponds to 137.5 µM dimenhydrinate. 21) This concentration is comparable with the IC 50 of 100 µM approximately for the human Kv1.5 blockade by dimenhydrinate in the present study (Fig.…”

CLS, PLS and PCR Methods in Different Sets of Data for Simultaneous Determination of Paracetamol and Orphenadrine Citrate in Their Combined Pharmaceutical Dosage Forms

“…Several methods have been reported for determination of PAR alone in biological matrix including spectrophotometric methods [13][14][15][16], HPLC methods [17][18][19][20][21], HPTLC method [22], GC method [23] and voltammetric methods [24][25][26]. On the other hand, only chromatographic methods have been reported for determination of ORP alone in biological matrix including HPLC method [27] and GC methods [28][29][30]. In addition, there is only one reported method for simultaneous determination of PAR & ORP in human serum by using HPLC method [31].…”

CLS, PLS and PCR Methods in Different Sets of Data for Simultaneous Determination of Paracetamol and Orphenadrine Citrate in Their Combined Pharmaceutical Dosage Forms

“…Several methods have been reported for determination of PAR alone in biological matrix including spectrophotometric methods [13][14][15][16], HPLC methods [17][18][19][20][21], HPTLC method [22], GC method [23] and voltammetric methods [24][25][26]. On the other hand, only chromatographic methods have been reported for determination of ORP alone in biological matrix including HPLC method [27] and GC methods [28][29][30]. In addition, there is only one reported method for simultaneous determination of PAR & ORP in human serum by using HPLC method [31].…”