title: Pharmacokinetics and bioavailability assessment of Miltefosine in rats using high performance liquid chromatography tandem mass spectrometry.
abstract: Miltefosine (MFS) is the first effective oral drug for treatment of visceral, mucosal and cutaneous leishmaniasis. In this study, liquid chromatography coupled mass spectrometry (LC-MS/MS) method of MFS was validated in rat plasma and its practical utilization to pharmacokinetic studies in rats for the first time. A rapid, selective and sensitive LC-MS/MS method for MFS in rat plasma was linear over the calibration range of 1-500ng/mL. MFS and Phenacetin (internal standard) were separated on Phenomenex Luna 3μ HILIC 200A (150×4.6mm) column under isocratic condition using methanol: 0.1% formic acid in triple distilled water, 90:10 (v/v) mobile phase at a flow rate of 0.8mL/min. The total chromatographic run time was 4.0min. The intra- and inter-day assay accuracy was observed between 99.45-102.88% and 99.92-101.58%, respectively. The intra- and inter-day assay precision was observed between 2.68-5.54% and 2.35-5.94%, respectively. The validated assay was practically applied to determine the plasma concentrations after oral and intravenous administration of MFS to rats. After oral administration, MFS showed Cmax (3200.00±95.39ng/mL) was observed at 12.00h (tmax) and t1/2 was 102.36±16.65h. The absolute bioavailability of MFS was 60.33±2.32%.
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Guru R
authors.initials: GR
authors.lastname: Valicherla
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Anees A
authors.initials: AA
authors.lastname: Syed
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Riyazuddin
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Athar
authors.initials: A
authors.lastname: Husain
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raibarelly, India.
authors.forename: Deep
authors.initials: D
authors.lastname: Javia
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raibarelly, India.
authors.forename: Kishan S
authors.initials: KS
authors.lastname: Italiya
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Prabhat R
authors.initials: PR
authors.lastname: Mishra
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: jr.gayen@cdri.res.in.
authors.forename: Jiaur R
authors.initials: JR
authors.lastname: Gayen
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine
keywords: Bioavailability; LC–MS/MS; Leishmaniasis; Miltefosine; Pharmacokinetics