Combined gas chromatographic-mass spectrometric procedure for the measurement of captopril and sulfur-conjugated metabolites of captopril in plasma and urine.
A gas chromatographic-mass spectrometric method is described for the simultaneous measurement of the novel anti-hypertensive drug captopril, and the following metabolites: captopril disulfide dimer, S-methyl captopril, and S-methyl captopril sulfone. With this method all derivatives can be chromatographed using conventional gas chromatography of hexafluoroisopropyl esters in one temperature-programmed run and these can then be quantitated using selected-ion monitoring techniques. Using urine or plasma, captopril, S-methyl captopril and the disulfide dimer of captopril in concentrations as low as 1 ng/ml, 10 ng/ml and 25 ng/ml, respectively can be detected. The reproducibility of the method is satisfactory both within-assay and inter-assay. This technique has demonstrated that the pattern of urinary excretion of these compounds in both man and rat was similar. Excretion of unchanged captopril, S-methyl captopril and the disulfide dimer over 6 h in man given captopril (50 or 100 mg) chronically was 18.3%, 0.97% and 3.06%, respectively. Corresponding excretion of these three compounds in the rat following a single 10 mg/kg dose was 18.3%, 2.69% and 1.8%, respectively. A possible sulfone oxidation product of S-methyl captopril was not detected in the urine of either man or rat.
D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D013045:Species Specificity
C038203:S-methylcaptopril; D011392:Proline; D002216:Captopril