Magnetic molecularly imprinted polymer nanoparticles for simultaneous extraction and determination of 6-mercaptopurine and its active metabolite thioguanine in human plasma.

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 1.0 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.

A historical perspective on the development of the cytarabine (7days) and daunorubicin (3days) treatment regimen for acute myelogenous leukemia: 2013 the 40th anniversary of 7+3.

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.

Separation of thiols as phenyl mercury derivatives by thin-layer chromatography. I. Azathioprine and 6-mercaptopurine metabolites.

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.