Sensitive gas chromatographic quantitation of zomepirac in plasma using an electron-capture detector.

A highly sensitive, specific and precise gas chromatographic method for the determination of the non-narcotic analgesic agent, zomepirac, in plasma is described. The pentafluorobenzyl ester derivative of zomepirac has been prepared. This enables the detection of zomepirac down to picogram levels using electron-capture detection. The lowest concentration of zomepirac which can be measured accurately and precisely (coefficient of variation less than 15%) is 5 ng/ml in a 2-ml plasma sample or 25 ng/ml in a 0.1-ml plasma sample. Two previously reported high-performance liquid chromatographic (HPLC) assays have detection limits of 50 ng/ml for 1-ml samples and 10 ng/ml for 2-ml samples, respectively. The present method is very useful when small sample size or interference is causing problems with the HPLC assay. This assay has been employed successfully in analyzing plasma samples from humans and monkeys as well as samples from rat milk.

The metabolism of zomepirac sodium. II. Isolation and identification of the urinary metabolites in rat, mouse, rhesus monkey, and man.

The metabolism of the oral analgesic agent, zomepirac sodium, sodium 5-(4-chlorobenzoyl)-1,4-dimethyl-1 H-pyrrole-2-acetate dihydrate, was studied in healthy male humans, rhesus monkeys, Wistar rats, and Swiss mice. The major urinary metabolites of zomepirac (Z) (80--95% of the dose) in these species were identified on the basis of a combination of chromatographic and spectroscopic data. Z was present as a major product in all species. Hydroxyzomepirac (HMZ) was a major component in rat and mouse, but a minor one in man, and it was absent in the monkey. 4-Chlorobenzoic acid (CBA) was identified as a major metabolite in rat (present as conjugates) and mouse and a minor one in monkey and man. Zomepirac glucuronide (ZG) was present as the major metabolite in man, monkey, and mouse, and present at trace levels in the rat. 4-Chlorohippuric acid, the glycine conjugate of CBA, was found in trace amounts only in the monkey. Thus, the metabolism of zomepirac in man and monkey is mainly characterized by glucuronide conjugation. The rat metabolizes zomepirac, mainly by oxidative pathways, to give HMZ and CBA. The mouse shows a balance of conjugation and oxidative pathways.