Determination of debrisoquine and metabolites in human urine by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric analysis has been developed for the determination of debrisoquine and its metabolites in the urine of healthy individuals (controls) and patients with chronic renal failure. The sensitive and specific assay comprises selected-ion monitoring of the drug and the metabolites 4-hydroxydebrisoquine and 8-hydroxydebrisoquine using guanoxan as the internal standard. The limit of detection is ca. 0.2 microgram/ml. The clinical study shows that the healthy individuals and patients with chronic renal failure can be divided in two groups of extensive metabolizers and poor metabolizers, respectively. The extensive metabolizers excreted large amounts of 4-hydroxydebrisoquine and minor amounts of 8-hydroxydebrisoquine. The poor metabolizers excreted small amounts of 4-hydroxy metabolite, and no 8-hydroxydebrisoquine was detected in the urine.

Structural analysis of 21-hydroxypregn-4-ene-3,20-dione (deoxycorticosterone) derivative compounds. Part II: Proton NMR spectra.

Complete analysis of the proton nuclear magnetic resonance spectrum of desoxycorticosterone (DOC) has been made using selective double irradiation, two-dimensional experiments, relaxation rate, and nuclear Overhauser effect measurements in order to specify the structure and conformation of products encountered during the preparation of the specific antigen DOC-bovine serum albumin (BSA). It has been shown that DOC has the normal P conformation with ring A half-chair, and ring B chair. This confirms results previously obtained by circular dichroism measurements.

Structural analysis of 21-hydroxypregn-4-ene-3,20-dione (deoxycorticosterone) derivative compounds. Part I: Synthesis and circular dichroism identification.

Deoxycorticosterone (DOC) derivative compounds (DOC, DOC 21-acetate, and 7-mercaptopropionic DOC) have been prepared and purified by high pressure liquid chromatography. Synthesis products have been identified, and three chromophores have been displayed by their n----II and II----II dichroic transitions. A normal half-chair conformation is favored in ring A.

Comparative effects of disopyramide and its mono-N-dealkylated metabolite in conscious dogs with chronic atrioventricular block: plasma concentration-response relationships.

In animals and humans, the antiarrhythmic agent disopyramide is primarily metabolized by mono-N-dealkylation. The effects of disopyramide and its N-dealkylated metabolite (MND) were investigated in 13 conscious dogs with chronic atrioventricular (A-V) block and implanted atrial pacing electrodes. Our data clearly show that both compounds used within the therapeutic plasma level range induced lengthening of the atrial effective refractory period (AERP) as reflected by the diminution of the maximal atrial frequency determined by pacing. However, at equivalent drug plasma concentrations, disopyramide induced a more marked decrease (1.2-1.7 times) in the maximal atrial frequency than did its metabolite. Both compounds increased mean arterial pressure (MAP) and atrial rate and decreased ventricular rate, but the effects on MAP and atrial rate were more marked with disopyramide than with MND. Thus, with regard to these cardiovascular parameters, the parent drug and MND possess distinct pharmacodynamic profiles, which may in part be related to their respective vagolytic power.

Determination of plasma testosterone by mass fragmentography using [3,4-13C]testosterone as an internal standard.

The combination of glass capillary gas chromatography--mass spectrometry is especially suitable for the recognition of compounds. The use of [3,4-13C]testosterone as internal standard, mass fragmentography and isotope ratio measurement have been applied to the quantitative determination of testosterone in plasma. This paper describes the method, using tert.-butyldimethylsilylmethoxime and di-heptafluorobutyrate derivatives. The calibration graph in isotopic dilution is examined. The results obtained are compared with the results obtained by radioimmunoassay. The sensitivity of the method is judged from the lower limit of detection: 4.5 pg. The precision, and inter- and intra-assay are calculated.