MIDAZOLAM - RADIOIMMUNOASSAY FOR PHARMACOKINETIC STUDIES IN MAN

  • 1 January 1982
    • journal article
    • research article
    • Vol. 37  (1) , 11-20
Abstract
A specific radioimmunoassay (RIA) for the determination of the new short-acting water soluble imidazo-1,4-benzodiazepine, midazolam [a sedative, anticonvulsant anxiolytic agent], directly in plasma was developed. Employing 3H-midazolam as the radioligand and a rabbit antiserum to a diazo conjugate of 5''-aminomidazolam and albumin, the method has a limited sensitivity of 2 ng/ml of midazolam using a 20 .mu.l sample of plasma. The intra- and interassay coefficients of variation ranged from 4 to 7% and 13 to 15%, respectively. The specificity of the RIA was established by demonstrating good agreement with both [electron capture-gas chromatography] and GC-MS [gas chromatography-mass spectrometry] procedures in the analysis of multiple clinical plasma samples. The utility of the RIA for the pharmacokinetic evaluation of midazolam is illustrated with plasma concentration profiles of the drug obtained in subjects who had received midazolam i.v., i.m. and orally.