Capillary gas chromatographic method for the determination of the thromboxane A2 receptor antagonist S-1452 and its metabolites in human urine.
A capillary gas chromatographic method using a sulphur-specific detector (Hall's electrolytic conductivity detector) was established to determine the thromboxane A2 antagonist S-1452 and its metabolites in human urine. The target species were the free acid (+)-S-145 of the drug and its nine metabolites: the three hydroxyl forms of (+)-S-145 (I, II and III), bis-nor-(+)-S-145 (IV) the hydroxylated forms of IV (V and VI), tetranor-(+)-S-145 (VII) and the hydroxylated forms of VII (VIII and IX). These ten compounds, which have the same sulphur-containing functional group in common, were determined simultaneously. Their conjugated forms, which were assumed to be glucuronides, were also assayed after hydrolysis. The first derivatization was esterification with diazomethane. The second, for the hydroxylated compounds, was trimethylsilylation with bis(trimethylsilyl)trifluoroacetamide. The ten analytes appeared as separate peaks without mutual interference during 5 min. Hall's detector distinguished the ten analytes selectively from the other urinary components, which removed the need for complex clean-up procedures and led to higher sensitivity with a lower noise level. The method is sensitive enough for the assay of substances present at more than 0.1 micrograms/ml of urine. All the compounds could be determined with a high level of precision and accuracy, with 2-5% relative standard deviation and within +/- 5% deviation from the actual value. Day-to-day measurements verified the reproducibility of the method. Recovered substances were quantified by following the time course, and the analytical data together with previously obtained plasma data clarified the metabolism pharmacokinetically.
Okamoto
J
J
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Hirai
E
E
Suzuki
Y
Y
Fujimoto
K
K
Kitagawa
T
T
Matsubara
T
T
D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics / Q000652:urine*; D002849:Chromatography, Gas; D005229:Fatty Acids, Monounsaturated / Q000493:pharmacokinetics / Q000652:urine*; D005965:Glucuronates / Q000097:blood; D006801:Humans; D006868:Hydrolysis; D007202:Indicators and Reagents; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000378:metabolism*
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D005965:Glucuronates; D007202:Indicators and Reagents; D017482:Receptors, Thromboxane; C056566:S 145; D013928:Thromboxane A2