Capillary gas chromatographic method for the determination of the thromboxane A2 receptor antagonist S-1452 and its metabolites in human plasma.
A capillary gas chromatographic method for the determination of a newly developed thromboxane A2 antagonist, S-1452, and its metabolites in human plasma has been developed. This nitrogenous compound was detected as the free acid (+)-S-145 using a nitrogen-phosphorus detector. The two metabolites bisnor-(+)-S-145 and tetranor-(+)-145 were also assayed. The three compounds, which all possess carboxylic acid group, were converted into their hexafluoro-2-propyl esters with hexafluoropropan-2-ol-pentafluoropropionic anhydride as reagent. The esterification resulted in a decreased background response from the detector, and hence higher sensitivity and better precision. The glucuronides of the three compounds were also assayed after alkaline hydrolysis. The plasma concentration of the glucuronide of I was more than twice that of the free acid. This method allows determination of the three compounds at more than 2 ng/ml with a precision of 2-6% and an accuracy variation of less than +/- 5%. The analysis was performed within 2 min after injection to assay the sample rapidly from the Phase I test. The method is suitable for pharmacokinetic studies.
Okamoto
J
J
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Hirai
E
E
Kitagawa
T
T
Matsubara
T
T
D001643:Bridged Bicyclo Compounds / Q000097:blood* / Q000493:pharmacokinetics; D002849:Chromatography, Gas; D005229:Fatty Acids, Monounsaturated / Q000097:blood* / Q000493:pharmacokinetics; 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