Tomiharu Ito

Determinatin of captopril in biological fluids by gas-liquid chromatography

Abstract The quantitation of captopril in biological fluids by gas-liquid chromatography using a flame photometric detector is described. Captopril was converted into an adduct with N-ethylmaleimide and then into hexafluoroiosopropyl ester. The latter derivative was separated on a 2% OV-210 column and determined by employing the captopril-N-hexylamaleimide adduct as an internal standard. The blood level and urinary excretion of captopril administered intravenuosly to dogs were measured by the proposed method.

Sensitive method for determination of captopril in biological fluids by gas chromatography—mass spectrometry

A sensitive method for the determination of captopril in blood and urine by gas chromatography-mass spectrometry is described. In order to prevent oxidative degradation of captopril, its sulph-hydryl group was immediately protected by treatment with N-ethylmaleimide (NEM), and the resulting NEM adduct was then converted into the bis(pentafluorobenzyl) derivative. Derivatized captopril was separated on a 2% OV-1 column, exhibiting a single peak of the correct theoretical shape. The detection limit was estimated to be 100 pg by using S-benzylcaptopril as an internal standard. The blood level and urinary excretion of unchanged captopril orally administered to dogs were determined by the proposed method. In addition, epimerization of the proline moiety and formation of the sulphoxide or sulphone through the esterification step are also described.

Determination of captopril and its disulphide in biological fluids

A gas chromatographic-mass spectrometric method for the simultaneous determination of captopril (SQ 14,255) and its disulphide (SQ 14,551) in biological fluids by means of selected ion monitoring is described. In order to prevent oxidative degradation, captopril was treated with N-ethylmaleimide (NEM). The captopril-NEM adduct and the disulphide were converted into the hexafluoroisopropyl esters, which were separated on a 10% Dexsil 300 GC column and determined by employing the captopril-N-butylmaleimide adducts as an internal standard. The blood and urine levels of captopril and its disulphide in dogs to which captopril had been administered orally were measured by the proposed method. The urinary excretion of these two substances in rats was also determined in a similar manner.

Determination of chinoform in biological fluids and nervous tissues of the dog by gas chromatography-mass spectrometry

A sensitive gas chromatographic-mass spectrometric method for the determination of 5-chloro-7-iodo-8-hydroxyquinoline (chinoform, clioquinol) in biological fluids and nervous tissues is described.Chinoform was converted into the pentafluorobenzyl ether, which was separated on a 10% Dexsil 300GC column and determined by the use of chinoform-d4 as an internal standard. The clean-up of chionoform in plasma and urine was efficiently achieved by extracting with benzene, while the drug in the tissue was pretreated successively by extraction with 12.5% v/v pyridine-benzene, separation on a Clin-Elut cartridge and adsorption on alumina.The quantitation limit of chinoform was 100pg, and the recovery rates of chinoform added to plasma and tissue were 98% and 92%, respectively. The chinoform levels in biological fluids and tissues in dogs after prolonged administration of the drug at a dose of 400 mg/kg/day were measured by the proposed method. The plasma level and tissue distribution of chinoform are also discussed.

Determination of isofloxythepin in biological fluids by gas chromatography-mass spectrometry

A method for the determination of isofloxythepin in biological fluids by gas chromatography-mass spectrometry is described. Isofloxythepin was readily converted into the trimethylsilyl ether by treatment with N,O-bis(trimethylsilyl)trifluoroacetamide. This derivative was separated on a 5% OV-101 column and determined, employing newly prepared isofloxythepin-d7 as an internal standard. Clean-up of isofloxythepin in blood and urine was efficiently achieved by back-extraction with hexane or hexane-toluene (9:1) under acidic and basic conditions, while isofloxythepin glucuronide in biological fluids was isolated by ion-exchange chromatography on Dowex 50W-X4 resin. The detection limit of isofloxythepin by this method was 50 pg. The blood and urine levels of isofloxythepin after oral administration of the drug to dogs were monitored by the proposed method.