Determination of captopril in human blood by gas chromatography-negative-ion chemical ionization mass spectrometry with [18O4]captopril as internal standard. 
A method for the quantitative measurement of captopril in human blood is described.  Blood was immediately treated with N-ethylmaleimide to prevent oxidative degradation.  The carboxyl moiety was derivatized to the pentafluorobenzyl ester, which shows excellent properties for negative-ion chemical ionization mass spectrometry.  A stable isotope-labelled standard was prepared from the intact target molecule in quantitative yield by exchanging the oxygen atoms of the free carboxylic acid and the imide moiety against 18O. The detection limit under negative-ion chemical ionization conditions is ca.  100 times lower than under electron-impact or positive-ion chemical ionization conditions, therefore only very small amounts of the original sample have to be analysed.  The method was applied to be quantitative determination of unchanged captopril in human plasma after oral administration of a 25-mg dose.