title: LC-MS/MS method development for quantification of busulfan in human plasma and its application in pharmacokinetic study.
abstract: A simple, rapid, specific and precise liquid chromatography-tandem mass spectrophotometric (LC-MS/MS) method was developed and validated for quantification of busulfan, in human plasma. busulfan d8 was used as internal standard, added to plasma sample prior to extraction using acetonitrile as a precipitating agent. Chromatographic separation was achieved on phenomenex kinetex C18 column (50mm×2.1mm, 2.6μm) with acteonitrile: 10mM ammonium formate buffer (80:20v/v) as an isocratic mobile phase with a flow rate of 0.5mLmin(-1). Quantitation was performed by transition of 264.1→151.1 (m/z) for busulfan and 272.1→159.1 (m/z) for busulfan d8. The lower limit of quantitation was 0.2ngmL(-1) with a 100μL plasma sample. The concentrations of nine working standards showed linearity between 0.2 and 100ngmL(-1) (r(2)≥0.9986). Chromatographic separation was achieved within 2.0min. The average extraction recoveries of 3quality control concentrations were 92.52% for busulfan and 90.75% for busulfan d8. The coefficient of variation was ≤15% for intra- and inter-batch assays. The developed method was successfully applied for the determination of Busulfan pharmacokinetics after oral administration.
authors.affiliation: Alkem Research center, MIDC Taloja, Navi Mumbai, Maharashtra, India.
authors.forename: Taraka Ramarao
authors.initials: TR
authors.lastname: Nadella
authors.affiliation: Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chandramoulipuram, Chowdavaram, Guntur 522019, Andhra Pradesh, India. Electronic address: svidyadhara@gmail.com.
authors.forename: Vidyadhara
authors.initials: V
authors.lastname: Suryadevara
authors.affiliation: Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chandramoulipuram, Chowdavaram, Guntur 522019, Andhra Pradesh, India.
authors.forename: Sasidhar Reddyvallam
authors.initials: SR
authors.lastname: Lankapalli
authors.affiliation: Krishna University, Machilipatnam, Andhra Pradesh, India.
authors.forename: Venkata Basaveswara Rao
authors.initials: VB
authors.lastname: Mandava
authors.affiliation: Vignan Pharmacy College, Vadlamudi, Guntur, Andhra Pradesh, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Bandarupalli
mesh_terms: D000284:Administration, Oral; D002066:Busulfan / Q000097:blood* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods / Q000639:trends; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods / Q000639:trends; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000639:trends
chemical_list: D002066:Busulfan
keywords: Busulfan; Busulfan d8; Human Plasma; LC–MS/MS; Validation