David Alkalay

Bioavailability and kinetics of maprotiline

Six male subjects received simultaneously single 50‐mg oral doses of a maprotiline hydrochloride tablet and a trideuterated maprotiline hydrochloride aqueous solution. No side effects or other problems were encountered. The blood levels of unlabeled and isotope‐labeled maprotiline for each subject were essentially superimposable. Peak levels, averaging about 50 ng/ml, were attained between 8 and 24 hr after drug. The biologic t½s (β‐phase) averaged 58 hr for the unlabeled and 60.5 hr for the labeled drug. The total areas under the curves (extended to time infinity) averaged 3,862 and 3,944 ng · hr/ml for maprotiline and trideuterated maprotiline, respectively (differences between the two are not significant). At the 95% degree of confidence the Westlake confidence limits show less than 10% differences between the formulations with respect to area under the curve data (calculated both to 168 hr and extended to time infinity), peak blood levels, and biologic t½s. There were no differences between formulations with respect to times of peak concentrations. Estimates were made for apparent volumes of distribution (about 1,000 l), apparent blood clearance (about 14 l/hr), lag times (about 1.42 hr for tablets and 1.31 hr for solution), and absorption rate constants (about 0.34 hr−1 for the tablets and 0.42 hr−1 for the solution).

Pharmacokinetics of Phenformin in Man

Phenformin was assayed in urine, plasma, and sputum specimens, obtained from two healthy volunteers during the four-day period following oral administration of a single therapeutic dose. Approximately one third of the drug was excreted unchanged in the urine. Phenformin profiles were obtained for urinary excretion rates and for plasma and saliva concentrations. The terminal exponential declines indicate a half-life of approximately 11 hours. At 37 degrees C, plasma bound 19 per cent of added phenformin.

Quantitation Of The Local Anesthetic Dibucaine With Gas Chromatography / Mass Spectrometry

Abstract A chemical ionization and an electron impact GC/MS assaying approach is presented for determining dibucaine concentrations in biological fluids. Both use deuterium-labeled drug as the internal standard and rely on the same sample extraction and sample preparation procedure. Under chemical ionization conditions (CH4), the assaying limits are in the range of 1–80 ng/ml of serum. Under electron impact conditions, the analytical range is 20–800 ng/ml. The chemical ionization procedure has been found suitable for monitoring drug levels in man. One volunteer, who received a single 5-mg oral dose, showed peak serum drug concentrations of 23 ng/ml attained 2 hr after drug administration. The biologic half-life (s phase) was 11 hr.

A Gas Chromatographic Assay for the Tetracyclic Antidepressant Maprotiline in Blood, Using Electron-Capture Detection

Abstract A procedure is described which permits the determination of maprotiline in biological fluids for concentrations in the range of 10 to 1000 ng/ml. It relies on the use of N-desmethylclomipramine as internal standard, on derivatization of the secondary amines with heptafluorobutyric anhydride, and the use of gas chromatography with electron-capture detection. The method is linear, specific, accurate and precise. It is suitable for routine analyses and is particularly applicable for monitoring the levels of maprotiline in the blood of patients treated for depressive illness.

Determination of the Dopamine Agonist CGS 15855A in Human Plasma by Gas Chromatography/Mass Spectrometry

Abstract A method is described for the determination of CGS 15855A in human plasma at concentrations ranging from 0.1 to 50 ng/ml. Deuterium labelled CGS 15855A is used as an internal standard. the procedure involves extraction of the compound followed by derivatization of the phenolic group with pentafluoropropionic anhydride. the resulting derivative is analyzed by gas chromatography/mass spectrometry using positive ammonia chemical ionization. the assay procedure is specific, accurate, and precise (overall mean percent recovery (± SD; 98.2 ± 7.3). It is suitable for routine analyses in preclinical and clinical studies.

Radioimmunoassay determinations of p-hydroxyphenformin and of apparent phenformin in human plasma or serum

Sensitive radioimmunoassay procedures are described for measuring p-hydroxyphenformin and apparent phenformin in human plasma or serum. The p-hydroxyphenformin procedure, which requires advance phenformin analysis, offers excellent accuracy. The determinations of apparent phenformin are influenced by the phenformin and p-hydroxyphenformin contents of the samples. Over a period of four months, the methods showed a precision associated with relative standard deviations of 12% for apparent phenformin and 13% for p-hydroxyphenformin.