[Determination of chlorzoxazone and its metabolite 6-hydroxychlorzoxazone in plasma by HPLC and their pharmacokinetics].
Linfeng Li, Y Zhang
Abstract
Linfeng Li, Y Zhang
Abstract
A rapid and sensitive HPLC assay was developed for the quantitation of chlorzoxazone and its metabolite 6-hydroxychlorzoxazone in plasma. These compounds, as well as internal standard 5-fluorobenzoxazolone, were extracted with ethyl acetate, then were analyzed on Alltima C18 column with a mobile phase of acetonitrile-0.5% acetic acid, and detected at 287 nm. The retention times of 6-hydroxychlorzoxazone, internal standard and chlorzoxazone were 6.12 min, 10.47 min and 18.65 min, respectively. The linearity of the method was tested in the concentration range 0.5-20 micrograms.ml-1, and the limits of detection of 6-hydroxychlorzoxazone and chlorzoxazone were found to be 0.2 and 0.5 microgram.ml-1, respectively. Inter-day and intra-day relative standard deviations (RSD) were below 8% and 11%. The recoveries of these two compounds were between 82.80%-100.76%. The pharmacokinetic profile of chlorzoxazone in human following an oral dose of 400 mg was studied. Both absorption and elimination of chlorzoxazone were found to be rapid in human. There seemed to be an obvious interindividual difference and perhaps an interracial difference as well, when compared with other races.
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A rapid and sensitive HPLC assay was developed for the quantitation of chlorzoxazone and its metabolite 6-hydroxychlorzoxazone in plasma. These compounds, as well as internal standard 5-fluorobenzoxazolone, were extracted with ethyl acetate, then were analyzed on Alltima C18 column with a mobile phase of acetonitrile-0.5% acetic acid, and detected at 287 nm. The retention times of 6-hydroxychlorzoxazone, internal standard and chlorzoxazone were 6.12 min, 10.47 min and 18.65 min, respectively. The linearity of the method was tested in the concentration range 0.5-20 micrograms.ml-1, and the limits of detection of 6-hydroxychlorzoxazone and chlorzoxazone were found to be 0.2 and 0.5 microgram.ml-1, respectively. Inter-day and intra-day relative standard deviations (RSD) were below 8% and 11%. The recoveries of these two compounds were between 82.80%-100.76%. The pharmacokinetic profile of chlorzoxazone in human following an oral dose of 400 mg was studied. Both absorption and elimination of chlorzoxazone were found to be rapid in human. There seemed to be an obvious interindividual difference and perhaps an interracial difference as well, when compared with other races.
Key concepts: Chlorzoxazone, Chemistry, Chromatography, Metabolite, Pharmacokinetics, High-performance liquid chromatography, Acetic acid, Ethyl acetate