Simple high-performance liquid chromatographic separation of oxazepam and its diastereoisomeric glucuronides in serum. Applications in a pharmacokinetic study in sheep.
This paper describes a highly specific and sensitive method for quantifying oxazepam and its diastereoisomeric 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 diastereoisomeric 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.
Mawa
R
R
Laboratoire de Biochimie, Pharmaco-Toxicologie et Analyse des Traces, Hôpital Edouard Herriot, Faculté de Pharmacie, Lyon, France.
Mis
D
D
Gagnieu
M C
MC
Grancher
D
D
Petit-Ramel
M
M
Bressolle
F
F
Vallon
J J
JJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D005965:Glucuronates / Q000097:blood* / Q000737:chemistry; D010076:Oxazepam / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D012756:Sheep; D013237:Stereoisomerism
D005965:Glucuronates; D010076:Oxazepam