A rapid & sensitive liquid chromatography- tandem mass spectrometry method for the quantitation of busulfan levels in plasma & application for routine therapeutic monitoring in haematopoietic stem cell transplantation.

dc.contributor.authorDesire, Salamun
dc.contributor.authorMohanan, Ezhil Pavai
dc.contributor.authorGeorge, Biju
dc.contributor.authorMathews, Vikram
dc.contributor.authorChandy, Mammen
dc.contributor.authorSrivastava, Alok
dc.contributor.authorBalasubramanian, Poonkuzhali
dc.date.accessioned2013-08-07T10:21:13Z
dc.date.available2013-08-07T10:21:13Z
dc.date.issued2013-04
dc.description.abstractBackground & objectives: Busulfan (Bu) in combination with cyclophosphamide is widely used in myeloablative conditioning regimen prior to haematopoietic stem cell transplantation (HSCT). Its narrow therapeutic range and toxic side effects at high systemic exposure and graft rejection at low exposure emphasize the need for busulfan dose optimization using targeted dose adjustment prior to HSCT. We report here a rapid and sensitive method to quantitate busulfan plasma levels in patients receiving busulfan as part of pre-transplant conditioning. Methods: The method involves simple protein precipitation of the plasma followed by analysis using a high performance liquid chromatography (HPLC) with tandem mass spectrometry - electrospray ionization technique (LC-ESI MS/MS) in positive ionization mode and quantified using multiple reaction monitoring (MRM). Deuterated busulfan (d8-busulf`an) was used as the internal standard. Results: The method was linear for the concentration ranging from 0 to 4000 ng/ml of busulfan with a limit of detection of 2 ng/ml and limit of quantitation of 5 ng/ml. The assay was accurate for serial concentrations of Bu in plasma for five consecutive days and the CV was less than 10 per cent. Conclusion: Using this rapid and sensitive method, busulfan levels were targeted and subsequent doses adjusted at our center in 26 patients receiving high dose busulfan in combination with cyclophosphamide or fludarabine.en_US
dc.identifier.citationDesire Salamun, Mohanan Ezhil Pavai, George Biju, Mathews Vikram, Chandy Mammen, Srivastava Alok, Balasubramanian Poonkuzhali. A rapid & sensitive liquid chromatography- tandem mass spectrometry method for the quantitation of busulfan levels in plasma & application for routine therapeutic monitoring in haematopoietic stem cell transplantation. Indian Journal of Medical Research. 2013 Apr; 137(4): 777-784.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/147780
dc.language.isoenen_US
dc.source.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724260/?report=classicen_US
dc.subjectBusulfanen_US
dc.subjectHSCTen_US
dc.subjectmass spectrometryen_US
dc.subjecttherapeutic monitoringen_US
dc.titleA rapid & sensitive liquid chromatography- tandem mass spectrometry method for the quantitation of busulfan levels in plasma & application for routine therapeutic monitoring in haematopoietic stem cell transplantation.en_US
dc.typeArticleen_US
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