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Biomedical subjects

M Jemal

Publications and source records attributed to M Jemal.

50 records · Page 3Linked to original sources

Simultaneous determination of the prodrug zofenopril and its active drug in plasma by capillary gas chromatography-mass-selective detection.

After oral administration of zofenopril, the active sulfhydryl angiotensin-converting enzyme inhibitor is released. Zofenopril is currently under clinical investigation as an antihypertensive. Blood samples are reacted with N-ethylmaleimide, immediately after collection, processed into plasma and stored frozen for subsequent analysis. After addition of two internal reference standards, one each for the prodrug and the active compound, the plasma samples are purified by a combination of liquid-liquid and solid-phase extractions. The dried methylated extracts are reconstituted with tetramethylbenzene and chromatographed by automated splitless injection on a fused-silica capillary column, connected to a mass-selective detector. The analytes and the internal reference standards are chromatographically resolved and a common fragment ion is monitored for the analytes. A limit of quantitation of approximately 1 ng/ml of plasma is achieved.

Angiotensin-Converting Enzyme Inhibitors↗

Determination of ethylenediaminetetra-acetic acid in aqueous rinses of detergent-washed rubber stoppers of pharmaceutical vials using solid-phase extraction and capillary gas chromatography.

A fused silica capillary gas chromatographic method is presented for the determination of traces of ethylenediaminetetra-acetic acid (EDTA) in aqueous rinses of rubber stoppers of pharmaceutical vials after treatment with detergents containing EDTA. Isolation and enrichment of EDTA from the aqueous medium is achieved using a commercially available strong anion-exchange solid-phase extraction cartridge, transformed to the formate form. A 2.0-ml volume of methanolic HCl is used for both elution of EDTA from the extraction column and formation of the tetramethyl ester derivative. With the incorporation of a methanolic wash to eliminate interfering components prior to elution with methanolic HCl, a limit of detection of 25 ng EDTA per ml water with a non-selective flame ionization detector is possible.

Journal Article↗

Determination of SQ 27,519, the active phosphinic acid-carboxylic acid of the prodrug SQ 28,555, in human serum by capillary gas chromatography with nitrogen-phosphorus detection after a two-step derivatization.

A method for the determination of SQ 27,519 (II), the active phosphinic acid-carboxylic acid of the prodrug SQ 28,555 (I), in human serum is presented. Compounds I and II are simultaneously extracted from acidified serum into ethyl acetate, and II is back-extracted into aqueous sodium bicarbonate. Compound I, in ethyl acetate, can be subsequently hydrolyzed and measured as II. The two acidic groups of II are selectively esterified, first by methylation of the carboxylic acid with methanolic hydrochloric acid and then by formation of the hexafluoroisopropyl ester of the phosphinic acid. The resulting product is measured by splitless-injection capillary gas chromatography with nitrogen-phosphorus detection. Linear standard curves were obtained for II with a detection limit of less than 10 ng/ml of serum. The method was successfully applied to the analysis of serum samples obtained from normal individuals after administration of I. In an ascending-dose study involving several human subjects the serum levels of II ranged from less than 10 to 7000 ng/ml of serum.

Chemical Phenomena↗

Simultaneous determination of captopril and S-benzoyl captopril in human blood by capillary gas chromatography-mass selective detection.

Using a new table-top electron-impact mass selective detector, interfaced with a narrow bore, fused silica capillary gas chromatograph, a method has been developed for the simultaneous determination of captopril and S-benzoyl captopril. With a capillary column the two components could be chromatographically resolved, thus permitting the use of electron-impact ionization for quantitative measurements.

Captopril↗

Demonstration of penicillamine as a product in benzylpenicillenic acid degradation in neutral media using differential pulse polarography.

During the study of the temporal changes of benzylpenicillenic acid in aqueous buffers using differential pulse polarography, penicillamine was found to be a degradation product at neutral pH. Since this result was not previously reported, the effects of pH and buffer concentration on penicillamine formation were investigated. The amount of penicillamine produced was greatest under conditions producing maximum benzylpenicillenic acid stability. Penicillamine was not obtained from benzylpenicilloic acid, the reported degradation product of benzylpenicillenic acid at neutral pH. Penicillamine also was detected in penicillin G solutions of neutral pH. Therefore, it is suggested that penicillamine found in penicillin G solutions arises from benzylpenicillenic acid degradation which, in turn, is produced from penicillin G isomerization. A pathway is proposed to show that penicillamine originates from the UV-absorbing isomer of benzylpenicillenic acid.

Chemical Phenomena↗