RESUMEN
Cytotoxic drugs used in cancer chemotherapy require the continuous monitoring of their plasma concentration levels for dose adjustment purposes. Such condition necessitates the presence of a sensitive technique for accurate extraction and determination of these drugs together with their active metabolites. In this study a novel solid phase extraction technique using magnetic molecularly imprinted nanoparticles (MMI-SPE) is combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) to extract and determine the anti-leukemic agent; 6-mercaptopurine (6-MP) and its active metabolite thioguanine (TG) in human plasma. The magnetic molecularly imprinted nanoparticles (Fe3O4@MIP NPs) were synthesized via precipitation polymerization technique and were characterized using different characterization methods A computational approach was adopted to help in the choice of the monomer used in the fabrication process. The Fe3O4@MIPs NPs possessed a highly improved imprinting efficiency, fast adsorption kinetics following 2nd order kinetics and good adsorption capacity of 1.0â¯mg/g. The presented MMI-SPE provided the optimum approach in comparison to other reported ones to achieve good extraction recovery and matrix effect of trace levels of 6-MP and TG from plasma. Chromatographic separation was carried out using a validated LC-MS/MS assay and recovery, matrix effect and process efficiency were evaluated. Recovery of 6-MP and TG was in the range of 85.94-103.03%, while, matrix effect showed a mean percentage recovery of 85.94-97.62% and process efficiency of 85.54-96.18%. The proposed extraction technique is simple, effective and can be applicable to the extraction and analysis of other pharmaceutical compounds in complex matrices for therapeutic drug monitoring applications.
Asunto(s)
Magnetismo , Mercaptopurina/sangre , Impresión Molecular/métodos , Nanopartículas/química , Polímeros/química , Extracción en Fase Sólida/métodos , Tioguanina/sangre , Cromatografía Líquida de Alta Presión/métodos , Humanos , Mercaptopurina/aislamiento & purificación , Tioguanina/aislamiento & purificaciónRESUMEN
This paper reviews the development of therapy for acute myelogenous leukemia that in 1973 led to the regimen of 7days of continuous intravenous arabinosylcytosine (cytarabine) and the first 3 concurrent days of intravenous daunorubicin, given the nickname "7+3." The state of leukemia treatment in the 1950s, 1960s and early 1970s is reviewed, the discovery of the two drugs in question described, and the introduction of clinical trials to reach an optimal regimen for their use delineated. During the 1950s, following World War Two and after a period of civil reconstitution, a national effort, facilitated by the U.S. Congress and federal investments in the National Cancer Institute, was initiated to enhance cancer therapy in the United States. The development of mouse models of leukemia and advances in understanding the structure and function of DNA and RNA and the process of cell proliferation provided new targets for drug development and new concepts for their use. The year, 2013, marks the 40th year that this protocol, 7+3, is the method of induction of remission for most patients with acute myelogenous leukemia. Its inadequacies also are made clear. Many patients with the disease die soon after diagnosis, and patients who have more unfavorable oncogenetic subtypes, intrinsically drug resistant cells, and greater intolerance to therapy make up the vast majority of the affected and few are cured. It is evident to all that new paradigms are needed if acute myelogenous leukemia is to be subdued in most patients with the disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/historia , Hematología/historia , Leucemia Mieloide Aguda/tratamiento farmacológico , Oncología Médica/historia , Adolescente , Adulto , Anciano , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Instituciones Oncológicas/historia , Manejo de Caso/historia , Niño , Ensayos Clínicos como Asunto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/historia , Ciclofosfamida/aislamiento & purificación , Ciclofosfamida/farmacología , Citarabina/administración & dosificación , Citarabina/efectos adversos , Citarabina/historia , Citarabina/aislamiento & purificación , Citarabina/farmacología , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Daunorrubicina/historia , Daunorrubicina/aislamiento & purificación , Daunorrubicina/farmacología , Perros , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Predicción , Francia , Haplorrinos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Masculino , Mercaptopurina/administración & dosificación , Mercaptopurina/efectos adversos , Mercaptopurina/historia , Mercaptopurina/aislamiento & purificación , Mercaptopurina/farmacología , Persona de Mediana Edad , National Institutes of Health (U.S.)/historia , Ratas , Inducción de Remisión , Estados UnidosRESUMEN
A method is described for converting thiol metabolites of azathioprine and 6-mercaptopurine into phenyl mercury derivatives. Separation of these derivatives was performed by chromatography on silica thin layers and they were detected by low temperature (--196 degrees) fluorescence. The parent compounds were regenerated on the chromatogram by spraying with 2 N HC1 and these were detected by low temperature fluorescence. Mercury was also detected in spots by spraying with dithizone. The method provides a simple solution to the problem of oxidation of thiol compounds during isolation procedures.