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Titolo:
Separation methods for methotrexate, its structural analogues and metabolites
Autore:
Rubino, FM;
Indirizzi:
Univ Milan, Osped S Paolo, Lab Analyt Mol Toxicol, Dept Med Surg & Odontol, I-20142 Milan, Italy Univ Milan Milan Italy I-20142 Med Surg & Odontol, I-20142 Milan, Italy
Titolo Testata:
JOURNAL OF CHROMATOGRAPHY B
fascicolo: 1-2, volume: 764, anno: 2001,
pagine: 217 - 254
SICI:
1387-2273(20011125)764:1-2<217:SMFMIS>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; THYMIDYLATE SYNTHASE INHIBITOR; HIGH-DOSE METHOTREXATE; FLUORESCENCE POLARIZATION IMMUNOASSAY; MASS-SPECTROMETRY DETECTION; ON-COLUMN CONCENTRATION; HUMAN-PLASMA; ELECTROCHEMICAL DETECTION; CEREBROSPINAL-FLUID;
Keywords:
reviews; methotrexate; folates;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
161
Recensione:
Indirizzi per estratti:
Indirizzo: Rubino, FM Univ Milan, Osped S Paolo, Lab Analyt Mol Toxicol, Dept Med Surg & Odontol, Via A Di Rudini 8, I-20142 Milan, Italy Univ Milan Via A Di Rudini 8 Milan Italy I-20142 Milan, Italy
Citazione:
F.M. Rubino, "Separation methods for methotrexate, its structural analogues and metabolites", J CHROMAT B, 764(1-2), 2001, pp. 217-254

Abstract

Methotrexate (MTX) is the prototype folate antagonist cytotoxic drug, employed in the therapy of solid tumors and leakaemias, and recently also as animmunosuppressive agent in organ transplantation, in the treatment of someautoimmune diseases and in the therapy of severe asthma. MTX is one of thevery few antineoplastic drugs the therapeutic concentration monitoring of which is currently employed in clinical practice and can be routinely measured in biological samples by a number of different analytical techniques, among which are immunoenzymatic and chromatographic methods. Each technique has of course its own advantages in terms of sensitivity, specificity, speed, cost and level of expertise required. Along with therapeutic drug concentration monitoring and clinical pharmacology, fundamental research into themechanism of action of antifolate drugs is still a field which requires the measurement of MTX, of its new analogues and of their metabolites in biological samples. This review summarizes the instrumental conditions and the performance of several published chromatographic methods employed to measure MTX, its metabolites and some analogues in clinical and biological research. More than 70 papers describing chromatographic assays for MTX and its metabolites have been published in the literature between 1975 and 2000. A wide array of experimental conditions for sample preparation, analyte separation and detection have been employed. According to their chemical properties, MTX, its metabolites and analogue drugs present in several biological samples (plasma, serum, saliva, urine, cerebrospinal fluid, tissue specimens) can be tn extracted, separated and detected under a variety of chromatographic conditions, i.e. on different stationary phases, under a wide choice of mobile phase conditions (acidic or neutral, employing ion-pair or micellar chromatography), followed by several detection techniques (UV-Vis spectrophotometry, pre- or post-column oxidation and fluorimetry, electrochemistry, mass spectrometry). Optimized methods allow simultaneous measurement within a few minutes of the plasma levels of MTX and its main metabolites at concentrations in the low-nM range. One special field which needs sensitive,fast and inexpensive methods for the detection and measurement of MTX is the monitoring of contamination in workplace environments, such as pharmaceutical industries and oncological hospital pharmacies, and in sewage waters. The measurement of the intracellular gamma -oligo-glutamate metabolites ofbiological folates, of MTX and of some analogue drugs is of great importance in basic pharmacological research. The existence of empirical quantitative relationships between the retention of individual oligomers under different chromatographic conditions and the number of added glutamic acid units allows identification of the metabolites even when authentic standards are not available. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 13:03:11