Determination of glibornuride (a tolylsulfonyl urea hypoglycemic agent) in blood by differential pulse polarography

Abstract

proach to ac polarography in the harmonic multiplex mode because it replaces numerous analog circuits, which require tuning, offset adjusts, etc., by a drift-free, highly automated digital program. On the other hand, because it places minimal demands on data acquisition capability, an analog conditioning approach such as the one used in this work is favored whenever digital data acquisition rates are too slow to meet the demands of digital signal conditioning-e.g., whenever one has to operate with a slob dedicated minicomputer system, or with a low-priority time shared terminal to a large computer or when applied signals of very high frequency are employed. ACKNOWLEDGMENTThe authors are indebted to Barry J. Huebert for helpful discussions and programming assistance.A sensitive and specific differential pulse polarographic assay was developed for the determination of glibornuride (a tolylsulfonylurea hypoglycemic a ent) in blood. It involves the selective extraction 09 the compound from whole blood into diethyl ether and back-extraction into 1. ON ",OH.Following suitable "clean-up" of the sample, the compound is nitrated in 10% KNOa/H2S04 at 105 O C for 2 hours. The nitro derivative is extracted into ethyl acetate, the residue is dissolved in 0.1N NaOH, deoxygenated, and analyzed by differential pulse polarography. The overall recovery of the assay is 80.7% i 8.0 (Std dev) from blood and the sensitivity limit is 0.05-0.10 pg/ml of blood (using a 2-ml sample per assay). The method was applied to the determination of blood levels of the intact drug in man following single oral doses of 50 and 100 mg of glibornuride.

Determination of Nitroimidazoles in Biological Fluids by Differential Pulse Polarography

“…Conditions for Polarographic Analysis-A polarographic analyzer' equipped with a drop timer2 was used in conjunction with a three-electrode polarographic cell comprised of a dropping mercury electrode, a saturated calomel electrode (SCE), and a platinum wire as the auxiliary electrode, as previously described (9). The drop time was 1.0 sec, and the drop mass was 2.32 mghec, where (m2/3) (t'l6) = 1.7525.…”

“…Transfer an 8-ml aliquot into a clean 50-ml tube, and add 2 ml Calculations-The current (microamperes) resulting from each peak and the overall recovery of each compound are determined as previously described (9), while the concentration of each component in the unknowns is determined from the respective internal standard curves.…”

“…Catalog No. A-412, Fisher Scientific Co., Fair Lawn, N.J.' Pharmaco, Publicker Industries Co., Linfield, Pa.* J. T. Baker Co., Phillipsburg, N.J 9. Brinkmann F254 silica gel G chromatoplate.…”

Determination of Clonazepam and Flunitrazepam in Blood and Urine by Electron-Capture GLC

“…Hydroxylation at the C-3 position also occurs, resulting in the elimination of these metabolites as their glucuronide and/or sulfate conjugates. The methods were applied to the determination of blood levels of clonazepam in man following single 2-mg oral doses (29,30) and of flunitrazepam in the dog following single 2-mg/kg doses by intravenous and oral routes (29). The 7-nitro-3hydroxy analogs of clonazepam and flunitrazepam, which are also hydrolyzed to the same benzophenones (Scheme I), are removed by selective solvent extraction prior to acid hydrolysis to ensure the Tables I and II specificity of the assay for the respective parent compounds.…”

Determination of Bromazepam in Blood by Electron-Capture GLC and of its Major Urinary Metabolites by Differential Pulse Polarography

“…A sensitive electron-capture GLC assay for the determination of bromazepam in blood, employing acid hydrolysis to the benzoylpyridine derivative (IV) (12), was not specific for bromazepam since metabolites I1 and 111, if present in blood, would also yield the same hydrolysis product (Scheme 1)and would interfere with the specificity of the assay. An improved assay was developed for the simultaneous determination of bromazepam and its MARVIN A. BROOKS, and CARL V. PUGLISI 3-hydroxy metabolite (11) as the intact 1,4-benzodiazepin-2-ones by a modification of published procedures (13,14). When using this modified procedure, it was shown that I1 was not measurable in the blood of subjects chronically treated with bromazepam.…”