Biomedical subjects

K K Midha

Publications and source records attributed to K K Midha.

At least 217 records · Page 12Linked to original sources

PubMed1977

High performance liquid chromatographic and mass spectrometric identification of dimethylxanthine metabolites of caffeine in human plasma.

High performance liquid chromatography and mass spectrometry were used to isolate and identify theophylline, theobromine and 1,7-dimethylxanthine (paraxanthine) in plasma of human volunteers following administration of 300 mg caffeine to methylxanthine-free volunteers. Plasma from these subjects was extracted and the dimethylxanthines were separated from each other and caffeine by high performance liquid chromatography. The effluents at the chromatographic peaks corresponding to the dimethylxanthine metabolites were collected, rechromatographed in a second system and the dried residues were subjected to mass spectrometry. By comparison of their retention times and mass spectra with those of authentic compounds, theophylline, theobromine and paraxanthine were positively identified as metabolic products of caffeine.

Caffeine↗

PubMed1977

GLC determination of plasma acenocoumarol levels.

A method for the quantitative estimation of acenocoumarol in plasma is described. Plasma containing acenocoumarol, to which a known amount of gamma-oxo derivative of phenylbutazone is added as an internal standard, is acidified and extracted with ethylene dichloride. The drug and the internal standard are then back-extracted into alkali, which, in turn, is acidified and reextracted with ethylene dichloride. The organic extract is evaporated and treated with an ethereal solution of diazomethane (100 microliter). The reacted mixture is evaporated, and the residue is dissolved in 25 microliter of carbon disulfide. Aliquots (2-3 microliter) are injected into a gas chromatograph equipped with a flame-ionization detector. The methyl derivatives of acenocoumarol and the internal standard give sharp, well-separated, symmetrical peaks. The method is of sufficient sensitivity to determine 0.25 microgram/ml of the drug in plasma with a relative standard deviation of 4%.

Acenocoumarol↗

PubMed1977

Identification of urinary catechol and methylated catechol metabolites of phenytoin in humans, monkeys, and dogs by GLC and GLC-mass spectrometry.

A catechol metabolite, 5-(3,4-dihydroxyphenyl)-5-phenylhydantoin, and a methylated catechol metabolite, 5-(3-methoxy-4-hydroxyphenyl)-5-phenylhydantoin, were identified as urinary metabolites in humans, monkeys, and dogs following the administration of phenytoin. These metabolites were separated from each other and from other known metabolites of phenytoin as n-butyl derivatives by GLC and positively identified by combined GLC-mass spectrometry.

Animals↗

PubMed1976

Gas chromatographic and mass spectrometric analysis of the products of methylation of sulfonylurea drugs.

Gas chromatographic analysis of the products of reaction of diazomethane with tolbutamide and chlorpropamide indicates the formation of three compounds in both cases. As expected, N-methylation (at sulfonamide nitrogen) is the predominant reaction; minor amounts of O-methylated product are also observed. The third product in both cases is the N-methylsulfonamide formed by decomposition of the N-methylated sulfonylurea during gas chromatography. Electron impact and chemulfonylurea during gas chromatography. Electron impact and chemical ionization mass spectrometric analysis, as well as 1H nuclear magnetic resonance examination of samples collected from gas chromatography, confirm the structural assignments. Additionally, proton magnetic resonance analysis of the crude reaction products established that N-methylsulfonamides are not formed in the course of the diazomethane reaction and that the O-methylated derivatives are true products of the reaction. The use of a paramagnetic shift reagent allowed direct estimation of the ratios of N- to O-methylation, and the demonstration that these ratios are not vitiated during gas chromatographic analysis.

Chemical Phenomena↗

PubMed1976

GLC identification and determination of 3,4-methylenedioxyamphetamine (MDA) from plasma and urine.

A GLC method for qualitative and quantitative determination of 3,4-methylenedioxyamphetamine in biological fluids is described. After extraction of the drug and the internal standard, 4-methoxyamphetamine, from plasma and urine, the solvent is evaporated and the residue is mixed with 20 mul of freshly distilled ether. Aliquots (1-2 mul) then are injected into the gas chromatograph. Both the drug and the internal standard give well-separated symmetrical peaks. Flame-ionization detection allows concentrations of 0.125 mug of 3,4-methylenedioxyamphetamine from plasma to be determined with a precision of 3.16%. The method is applicable to the estimation of 4-methoxyamphetamine, employing 3,4-methylenedioxyamphetamine as the internal standard. For identification purposes, various derivatives such as Schiff bases, isothiocyanates, trifluoroacetates, and heptafluorobutyrates of both compounds were formed following extraction from urine and their GLC behavior was investigated. Derivative formation was confirmed by GLC-mass spectrometry. Mass spectral data for these derivatives are presented.

Amphetamines↗

PubMed1976

GLC determination of plasma concentrations of phenprocoumon.

A GLC method for the quantitative estimation of phenprocoumon from plasma is described. Plasma containing phenprocoumon, to which a known amount of phenytoin is added as the internal standard, is acidified and extracted with ethylene dichloride. The drug and the internal standard are then back-extracted into alkali, which is acidified and reextracted with ethylene dichloride. The organic extract is evaporated, and the evaporated residue is mixed with 50 mul of trimethylanilinium hydroxide in methanol. Aliquots (1-2 mul) are injected into a gas chromatography equipped with a flame-ionization detector in which the injection port is held at 325 degrees. The methyl derivatives of phenprocoumon and the internal standard give sharp, well-separated, symmetrical peaks. The method is of sufficient sensitivity to determine 0.125 mug/ml of the drug in plasma with a coefficient of variation of 7%.

Alkylating Agents↗

PubMed1976

GLC determination of plasma levels of intact chlorpropamide or tolbutamide.

A GLC procedure was developed for the quantitative estimation of intact chlorpropamide and tolbutamide concentrations in plasma; the drugs are used as mutual internal standards. After extraction of plasma containing the drug and internal standard with toluene, the dried residue is treated with ethereal diazomethane to form the methyl derivatives of tolbutamide and chlorpropamide. Aliquots of the ethereal solution are injected into a gas chromatograph equipped with a glass-lined injection port and glass column packed with a phenyl methyl silicone fluid (OV-25) on Chromosorb W, which facilitates the intact determination of the methyl derivatives of the drugs. The response to the flame-ionization detector was linear over a range of 0.20-25 mug/ml, with a 0.05-mug/ml limit of detectability for both drugs. The method compares favorably with a recently developed high-pressure liquid chromatographic procedure and is adequate for following blood level profiles of single doses of chlorpropamide (125 mg) and tolbutamide (250 mg). Mass spectral evidence showing that intact sulfonylureas are measured is presented.

Biological Availability↗

PubMed1976

Sensitive GLC procedure simultaneous determination of phenytoin and its major metabolite from plasma following single doses of phenytoin.

An improved GLC procedure was developed for the simultaneous determination of phenytoin and its metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, in plasma and urine following enzyme hydrolysis. After extraction, the drug, the metabolite, and the internal standard, 5-(p-methylphenyl)-5-phenylhydantoin, are measured by GLC with flame-ionization detection as their respective methyl derivatives following flash-heater methylation with trimethylanilinium hydroxide. The drug and metabolite give well-resolved symmetrical peaks on a phenyl methyl silicone column, and the method has a sensitivity of 150 ng/ml of phenytoin and 125 ng/ml of the metabolite. GLC-mass spectral evidence is presented for the formation and intact determination of methyl derivatives of the drug, its metabolite, and the internal standard.

Administration, Oral↗

PubMed1976