Major Metabolites In Biological Fluids Research Articles

Evolving bioanalytical methods for the cardiovascular drug bosentan

The history of the development of analytical methods for the determination of the cardiovascular agent bosentan, and its three major metabolites in biological fluids is described. Before the advent of LC-MS-MS, conventional HPLC-UV methodology was adequate for the determination of the drug alone in samples generated from toxicology studies. The progressive changes in the methods described reflect improvements in MS instrumentation and software, the need for measuring metabolites, as well as the availability of deuterated internal standards. Finally, three LC-MS-MS methods were chosen as being suitable for routine use. The most sophisticated of these (E), involving protein precipitation, liquid-liquid extraction, and on-line solid phase extraction by automated column switching, allowed the simultaneous and sensitive determination of the drug and three metabolites in a variety of biological matrices from several species to support pharmacokinetic studies. Two further, simpler, MS methods were developed (F and G) which, compared with the sophisticated method, focussed on reduced manual effort and reduced instrumental run cycle times. The limits of quantitation were between 1 and 2 ng mL−1 for bosentan and the three metabolites.

High-performance liquid chromatographic separation of the enantiomers of hydroxychloroquine and its major metabolites in biological fluids using an α 1-acid glycoprotein stationary phase

An enantioselective two-stage off-line assay has been developed for the analysis of hydroxychloroquine and its three major metabolites in biological fluids. The first non-stereoselective stage of the assay (PRP-1 column) separates and quantitates parent drug and metabolites. Fractions containing hydroxychloroquine and each of the metabolites are collected manually, evaporated, reconstituted in mobile phase and reinjected onto an α 1-acid glycoprotein column to separate and determine proportions of individual enantiomers. Preliminary results from patient samples indicate that the disposition of hydroxychloroquine and its major metabolites is enantioselective.

SIMULTANEOUS DETERMINATION OF CARBAMAZEPINE AND ITS MAJOR METABOLITES IN HUMAN PLASMA AND URINE BY HPLC

A method is described for the analysis of carbamazepine and its major metabolites in biological fluids. The method uses a HPLC system based on a C18 Partisil column. The metabolites were extracted from chloroform in the presence of an internal standard. The method was specific, precise and reproducible.

High-Performance Liquid Chromatographic Assay for Chlorquine and its Two Major Metabolites, Desethylchloroquine and Bidesethylchloroquine in Biological Fluids

Abstract A high-performance liquid chromatography (HPLC) method for the determination of chloroquine and its two major metabolites in biological fluids is described. Hydroxychloroquine is used as an internal standard (I.S.). Drug, metabolites and I.S. were extracted as bases with diethyl ether by a single step procedure. After drying and evaporation of the organic phase, the residue was dissolved into the mobile phase and injected into the chromatographic system. Separation was performed using a normal phase column (Inertsil sill with mixture of acetonitrile, methanol and ammonia as mobile phase. The detection was carried out by fluorescence measurement : excitation wavelength was set at 325 nm and emission at 380 nm. The limit of detection was near 3.7 ng ml−1 for chloroquine and metabolites. No chromatographic interference could be detected by endogenous compounds or other antimalarial drugs. Because of the good accuracy of the method, concentrations were determinated with a relative standard deviation ...

Assay method for the simultaneous determination of proguanil, chloroquine and their major metabolites in biological fluids

Assay method for the simultaneous determination of proguanil, chloroquine and their major metabolites in biological fluids

Specific Determination of Hydroquinidine and Its Major Metabolites in Biological Fluids by High Performance Liquid Chromatography

Abstract A specific assay have been developed for the determination of dihydroquinidine (DHQ) and its major metabolites : 11-hydroxy-dihydroquinidine (11-OH DHQ), 3 (S) 3-hydroxydihydroquinidine (3-OH DHQ), dihydroquinidine 1-N-oxide (DHQ N-oxide) in human urine and plasma. The assay uses a reverse phase high performance liquid chromatographic system with fluorescence detection; the mobile phase consists of acetonitrile-acetic acid-water (7:4:89). After adding internal standard, biological samples (0.5ml) are extracted at alkaline pH by methylene chloride-iso-propanol (8:2). The organic extract is dehydrated and evaporated, the residue dissolved in 150 μl mobile phase and an aliquot injected onto the column. Lower limits of sensitivity range from 1 ng of 11-OH DHQ to 15 ng of DHQ. The standard curves are linear and results are reproducible over the concentration ranges : DHQ 0.1 to 3 μg/ml, 11-OH DHQ 2.5 to 250 ng/ml, 3-OH DHQ 10 to 1000 ng/ml and DHQ N-oxide 5 to 500 ng/ml. The assays have been tested successfully in pharmacokinetic and metabolic studies of dihydroquinidine.

Assay of isradipine and of its major metabolites in biological fluids by capillary gas chromatography and chemical ionization mass spectrometry

A method is described for the determination of isradipine, a dihydropyridine calcium antagonist, and five of its metabolites in plasma and urine. The neutral compounds were extracted in toluene and analysed in a wide-bore silica capillary column. The acidic compounds were extracted in two steps, then esterified with diazomethane and assayed separately using the same column. Detection was performed by negative-ion mass spectrometry with chemical ionization. The limit of detection of isradipine was 0.04 ng/ml when the compound was determined alone and 0.7 ng/ml when its oxidized metabolite was determined simultaneously. The limits of detection of the metabolites in plasma ranged from 0.15 to 2 ng/ml. The method was successfully used in conventional pharmacokinetic studies and in a multicentre study of population pharmacokinetics.

Gas chromatographic method for determination of a piperazine derivative (trelibet®) and its metabolites in human plasma and urine

A sensitive gas chromatographic method was developed for the determination of Trelibet®, 1-benzyl-4-(2′-pyridinecarbonyl)piperazine, and of its major metabolites in biological fluids. The compounds were extracted as bases into dichloromethane, and the extracts were analysed by a dimethylsilicone capillary column with a nitrogen—phosphorus flame-ionization detector. The lower limit of detection was 1 ng/ml for Trelibet and 5 ng/ml for the metabolites. Peak-area ratios of the compounds and internal standard were linearly correlated to their plasma concentrations between 1 and 1000 ng/ml. The method was used for quantification of Trelibet and two of its metabolites in depressed patients after oral administration of a single dose of 200 mg of Trelibet. Concentration data measured in plasma and urine showed that the method is sensitive enough to monitor concentrations both for pharmacokinetic studies and for plasma steady-state levels daily.

High-performance liquid chromatographic determination of ibuprofen and its major metabolites in biological fluids

A sensitive and selective high-performance liquid-chromatographic assay for ibuprofen and its major metabolites in biological fluids is described. To ensure good chromatographic separation the drug and metabolites were run on a gradient elution system and detected with a variable wavelength detector set at 220 nm. A second, more rapid, isocratic system is also described for the detection of only ibuprofen.

A rapid and specific semi-micro method involving high-pressure liquid chromatography for the assay of metronidazole in plasma, saliva, serum, urine and whole blood.

British Journal of Clinical PharmacologyVolume 9, Issue 5 p. 528-529 Free Access A rapid and specific semi-micro method involving high-pressure liquid chromatography for the assay of metronidazole in plasma, saliva, serum, urine and whole blood. CM Kaye, CM KayeSearch for more papers by this authorMG Sankey, MG SankeySearch for more papers by this authorLA Thomas, LA ThomasSearch for more papers by this author CM Kaye, CM KayeSearch for more papers by this authorMG Sankey, MG SankeySearch for more papers by this authorLA Thomas, LA ThomasSearch for more papers by this author First published: May 1980 https://doi.org/10.1111/j.1365-2125.1980.tb05856.xCitations: 36AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References BROGDEN, R.N., HEEL, R.C., SPEIGHT, T.M. & AVERY, G.S. (1978). Metronidazole in anaerobic infections: a review of its activity, pharmacokinetics and therapeutic use. Drugs, 16, 387– 417. GUDAUSKAS, G.A., PALCIC, B. & KONG, S. (1978). The determination of misonidazole, metronidazole and Ro-9963, a class of radiosensitizing agents by HPLC in plasma and urine. Clin. Biochem., 11, P– 8. GULAID, A., HOUGHTON, G.W., LEWELLEN, O.R.W., SMITH, J. & THORNE, P.S. (1978). Determination of metronidazole and its two major metabolites in biological fluids by high pressure liquid chromatography. Br. J. clin. Pharmac., 6, 430– 432. HOUGHTON, G.W., THORNE, P.S., SMITH, J., TEMPLETON, R. & COLLIER, J. (1979). Comparison of the pharmacokinetics of metronidazole in healthy female volunteers following either a single oral or intravenous dose. Br. J. clin. Pharmac., 8, 337– 341. LANBECK, K. & LINDSTROM, B. (1979). Determination of metronidazole and tinidazole in plasma and faeces by high-performance liquid chromatography. J. Chromatogr., 162, 117– 121. MARQUES, R.A., STRAFFORD, B., FLYNN, N. & SADEE, W. (1978). Determination of metronidazole and misonidazole and their metabolites in plasma and urine by high-performance liquid chromatography. J. Chromatogr., 146, 163– 166. STAMBAUGH, J.E., FEO, L.G. & MANTHEI, R.W. (1968). The isolation and identification of the urinary oxidative metabolites of metronidazole in man. J. Pharmac. exp. Ther., 161, 373– 381. WHEELER, L.A., de MEO, M., HALULA, M., GEORGE, L. & HESELTINE, P. (1978). Use of high-pressure liquid chromatography to determine plasma levels of metronidazole and metabolites after intravenous administration. Antimicrobial Agents Chemother., 13, 205– 209. WORKMAN, P., WILTSHIRE, C.R., PLOWMAN, P.N. & BLEEHEN, N.M. (1978). Monitoring salivary misonidazole in man: a possible alternative to plasma monitoring. Br. J. Cancer, 38, 709– 718. Citing Literature Volume9, Issue5May 1980Pages 528-529 ReferencesRelatedInformation

High-pressure Liquid Chromatographic Determination of Chlordiazepoxide and its major Metabolites in Biological Fluids

A simple, isocratic, reversed-phase, high-pressure liquid chromatographic procedure was developed for the determination of chlordiazepoxide and its major metabolites in plasma and urine. The within-run coefficient of variation was 3.4-8.0%, and the day-to-day variation was 4.0-8.0%. Recoveries of 80-91% with sensitivity limits of 50 ng/ml were obtained for the parent drug and its metabolites. Plasma and urine samples collected after single intravenous and single oral doses were analyzed using this procedure.

Determination of metronidazole and its two major metabolites in biological fluids by high pressure liquid chromatography.

Determination of metronidazole and its two major metabolites in biological fluids by high pressure liquid chromatography.

A simple method for determining diazepam and its major metabolites in biological fluids: application in bioavailability studies.

Abstract: A simple gas chromatographic analytical method for determining diazepam and its major metabolites in the blood, urine, and muscle homogenate is described. Its applicability is illustrated by bioavailability studies, on man and on animals. The human studies revealed equivalence between two marketed brands of diazepam tablets and a slight difference between two brands of suppositories. The animal experiments showed agreement of in vivo properties of two different formulations of a diazepam injection fluid.