Determination of midazolam (Versed) and its metabolites in plasma by high-performance liquid chromatography. 1985

C V Puglisi, and J Pao, and F J Ferrara, and J A de Silva

A rapid, sensitive and selective high-performance liquid chromatographic (HPLC) assay was developed for the determination of midazolam, 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]- benzodiazepine (I), and its four metabolites in plasma. The assay involves extraction into diethyl ether--methylene chloride (7:3) from plasma buffered to pH 9 and subsequent analysis by reversed-phase HPLC with ultraviolet detection at 254 nm. The overall recovery of I from dog plasma was 94.5 +/- 7.1% and greater than 89.0% for its metabolites. The sensitivity limit of the assay was 50 ng/ml of plasma for all compounds. The HPLC assay was used to determine plasma concentrations of I and its metabolites from selected samples taken from an oral toxicity study in the dog.

UI MeSH Term Description Entries
D008297 Male Males
D008874 Midazolam A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. Dormicum,Midazolam Hydrochloride,Midazolam Maleate,Ro 21-3981,Versed,Hydrochloride, Midazolam,Maleate, Midazolam,Ro 21 3981,Ro 213981
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001569 Benzodiazepines A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring. Benzodiazepine,Benzodiazepine Compounds
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

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