title: Development and validation of a liquid chromatography/tandem mass spectrometry assay for the quantification of methyl protodioscin in rat plasma: application to a pharmacokinetic study.
abstract: A high performance liquid chromatography/tandem mass spectrometry assay was first developed and validated for the quantification of methyl protodioscin (MPD), a natural furostanol saponin with distinct antitumor activity, in rat plasma with 17alpha-ethinylestradiol as internal standard (IS). Methanol-mediated protein precipitation was employed for plasma sample pretreatment. The separation was achieved on a C(18) column (150 x 4.6 mm, i.d., 5 microm) by isocratic elution with methanol-water (72:28, v/v) as mobile phase at a flow rate of 1.0 mL/min. Ion acquisition was performed in selective reaction monitoring positive mode by monitoring the transition of m/z 1085.7 --> 1053.7 for MPD, and in selective ion monitoring negative mode by monitoring the deprotonated ion m/z 295.5 for IS. The assay was linear over the concentration range of 2.024-270.0 microg/mL with 2.024 microg/mL as the lower limit of quantification. It was specific, accurate, precise and reproducible with intra- and inter-run RSD <8.3% and RE between -11.5 and 12.8%. The assay was successfully applied to a preclinical pharmacokinetic study after an intravenous dose of 40 mg/kg MPD to rats.
authors.affiliation: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Wenhua-Road 103, Shenyang 110016, People's Republic of China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Cao
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yao
authors.forename: Haifeng
authors.initials: H
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.forename: Pinghua
authors.initials: P
authors.lastname: Sun
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004144:Diosgenin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D015394:Molecular Structure; D051381:Rats; D015203:Reproducibility of Results; D012503:Saponins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D012503:Saponins; C425324:methyl protodioscin; D004144:Diosgenin