Simple high-performance liquid chromatographic separation of oxazepam and its diastereoisomeric glucuronides in serum Applications in a pharmacokinetic study in sheep |
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| Authors: | Roger Mawa Dominique Mis Marie Claude Gagnieu Denis Grancher Michelle Petit-Ramel Françoise Bressolle Jean-Jacques Vallon |
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| Institution: | aLaboratoire de Biochimie, Pharmaco-Toxicologie et Analyse des Traces, Hôpital Edouard Herriot et Laboratoire de Chimie Analytique III, Faculté de Pharmacie, 69437 Lyon Cedex 03, France;bLaboratoire de Nutrition, Ecole Nationale Vétérinaire de Lyon, 69280 Marcy L'Etoile, France;cLaboratoire de Chimie Analytique II, Université Claude Bernard Lyon I, 69622 Villeurbanne Cedex, France;dLaboratoire de Pharmacocinétique, Faculté de Pharmacie, 34060 Montpellier Cedex 01, France;eLaboratoire de Pharmacocinétique, Hôpital Carémeau, 30006 Nîmes, France |
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| Abstract: | This paper describes a highly specific and sensitive method for quantifying oxazepam and its diastereoisometric glucuronides in serum. The method involves sample clean-up by solid-phase extraction on C18 cartridge followed by quantitation on a reversed-phase HPLC column. Diazepam is used as internal standard. Extraction recovery from serum proved to be more than 86%. Precision, expressed as C.V., was in the range 1.2–9.5%. The limits of quantification were 40, 400, and 200 nmol/l for oxazepam, S-(+)- and R-(−)-glucuronides, respectively. This method was applied to the determination of oxazepam and its diastereoisometric glucuronides in serum collected during a pharmacokinetic study performed in sheep after oral administration of racemic oxazepam. S-(+)/R-(−) ratios were measured all along the sampling time collection and the pharmacokinetic parameters were determined. |
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| Keywords: | Oxazepam Oxazepam glucuronide Benzodiazepines |
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