Gas chromatographic-mass spectrometric quantitation of busulfan in human plasma for therapeutic drug monitoring: a new on-line derivatization procedure for the conversion of busulfan to 1,4-diiodobutane.
A simplified gas chromatographic-mass spectrometric (GC-MS) analytical method, involving a novel derivatization procedure was developed for monitoring busulfan (Bu) plasma concentrations in populations undergoing bone marrow transplantation. Plasma samples (500 μL) containing Bu-d8 as internal standard were extracted with ethyl acetate (2 mL) followed by centrifugation (1800 rpm, 5 min) and evaporation of the organic layer under nitrogen flow (50 °C). The dry residue was reconstituted with 100 μL iodine solution in acetonitrile (0.25%, w/v) and 3 μL were injected into the GC-MS system at 250 °C. Conversion of Bu to 1,4-diiodobutane was accomplished on-line without the need of an extra derivatization step. MS was operated at selected ion monitoring mode at m/z 183 and 191 corresponding to Bu and Bu-d8 derivatives. Total analysis time was 11.5 min. Calibration curves were linear (mean r=0.9996) over a concentration range of 25-3651 ng/mL using a (1/x)-weighted scheme. Limit of detection and lower limit of quantitation were 10.6 and 25 ng/mL, respectively. Overall accuracy Er (%) was ranging from -5.10% to 10.5%. Within- and between-run RSD (%) were lower 4.51% and 2.15%, respectively. Overall recovery of Bu was equal to 69.3±4.56% (RSD (%)). The present method is sensitive and specific, requiring a simple sample preparation procedure and short analysis time, advantages crucial for therapeutic drug monitoring of Bu in clinical practice and application in pharmacokinetic studies.
['Athanasiadou|Ioanna|I|', 'Angelis|Yiannis S|YS|', 'Lyris|Emmanouil|E|', 'Archontaki|Helen|H|', 'Georgakopoulos|Costas|C|', 'Valsami|Georgia|G|']
D018906:Antineoplastic Agents, Alkylating D002066:Busulfan D002138:Calibration D016903:Drug Monitoring D008401:Gas Chromatography-Mass Spectrometry D006801:Humans D006847:Hydrocarbons, Iodinated D057230:Limit of Detection D013058:Mass Spectrometry D015203:Reproducibility of Results D013997:Time Factors
Busulfan Human plasma Therapeutic drug monitoring Gas chromatography Mass spectrometry