RESUMO
Determination of busulfan concentration in patients undergoing bone marrow transplantation is necessary in order to reduce toxic effects and/or graft rejection due to unadjusted dose exposure. A new extraction method namely dispersive micro solid phase extraction (DMSPE) based on mesoporous sorbent was used for cleaning-up the plasma samples. DMSPE coupling with liquid chromatography with tandem mass spectrometry (LC-MS/MS) was implemented for the determination of busulfan dosage in plasma samples. The linear range was found from 10 to 2000 ng/ml. The precision and accuracy were found better than 15% according to Food and drug Administration (FDA) guideline. This method was successfully used to determine the busulfan in patients administrated busulfan as part of the preparative regimen for bone marrow transplantation.
Assuntos
Bussulfano/isolamento & purificação , Imunossupressores/isolamento & purificação , Microextração em Fase Sólida/métodos , Adsorção , Bussulfano/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Imunossupressores/sangue , Plasma/química , Espectrometria de Massas em TandemRESUMO
A gas-chromatographic assay method was developed and validated for determination of busulfan in human plasma for test dose therapeutic drug monitoring. Busulfan and the internal standard (1,6-bis-(methanesulfonyloxy)hexane) were extracted from plasma samples and derivatized with 2,3,5,6-tetrafluorothiophenol prior to gas chromatographic determination. The 63Ni electron-capture detector provided a limit of quantitation of 0.0100 micrograms ml-1 busulfan in plasma with a linear response over the concentration range 0.0100-0.400 micrograms ml-1. Extraction and derivatization yields were 85.3%-91.0% and greater than 95%, respectively. Assay specificity for busulfan in the presence of potential metabolites was demonstrated. Potentially co-administered drugs gave no response under the sample preparation and chromatographic conditions described for quantification of busulfan. The applicability of this assay to the individualization of busulfan therapy based on a 2 mg test dose is discussed.
Assuntos
Antineoplásicos Alquilantes/sangue , Bussulfano/sangue , Cromatografia Gasosa/métodos , Antineoplásicos Alquilantes/análise , Antineoplásicos Alquilantes/isolamento & purificação , Bussulfano/análise , Bussulfano/isolamento & purificação , Calibragem , Monitoramento de Medicamentos , Humanos , Fenóis/química , Análise de Regressão , Reprodutibilidade dos Testes , Compostos de Sulfidrila/química , Tiofenos/sangue , Tiofenos/químicaRESUMO
Busulphan [1,4-bis(methanesulfonoxy)butane], an alkylating agent used in the treatment of chronic myelocytic leukemia, was labeled with the positron-emitting radionuclide carbon-11 in a four-step synthetic procedure [1-11C]4-Hydroxybutyronitrile was obtained in 60-70% yield by the reaction of [11C]cyanide with 3-bromopropanol. The nitrile was hydrolysed to [1-11C]gamma-butyrolactone (80-90% yield) with sulfuric acid. Solid phase extraction was used to isolate the lactone and change the solvent before reduction to [1-11C]1,4-butanediol. Dimesylation of the diol with methanesulfonyl chloride in dichloromethane/pyridine yielded [1-11C]busulphan with conversions in the order of 30-35%. The total time of synthesis, including HPLC purification, was 65-75 min from the end-of-trapping of [11C]ammonium cyanide. The decay-corrected isolated yield of no-carrier-added [11C]busulphan was 4-7% and the radiochemical purity was better than 99%.
