title: Development and validation of an LC-MS-MS method for determination of methyl kulonate in rat plasma.
abstract: A sensitive, rapid and specific LC-MS-MS method was established and validated for determination of methyl kulonate, a major bioactive constituent isolated from Meliae Cortex, in rat plasma. Plasma samples were treated by precipitating protein with methanol and were chromatographed using a Capcell Pak C₁₈ column (100 x 4.6 mm, 5 μm) with the mobile phase comprising a mixture of methanol, 10 mM ammonium formate and formic acid (95:5:0.1, v/v/v). Detection and quantification were performed by mass spectrometry in the multiple reaction monitoring mode with positive atmospheric ionization at m/z 467 --> 311 for methyl kulonate, and m/z 469 --> 451 for dubione B (internal standard), respectively. A good linear response was observed over the concentration range 1.00-500 ng/mL with the lower limit of quantification 1.00 ng/mL in rat plasma. The method also afforded satisfactory results base on sensitivity, specificity, precision, accuracy, recovery, freeze-thaw and long-time stability. The validated method was successfully applied to determine the pharmacokinetic properties of methyl kulonate in rats after oral administration at dose of 100 mg/kg. This pharmacokinetic study of methyl kulonate is reported here for the first time.
authors.affiliation: Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan 250062, People's Republic of China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Deng
authors.forename: Tao
authors.initials: T
authors.lastname: Yuan
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Cui
authors.forename: Shaochao
authors.initials: S
authors.lastname: Liu
authors.forename: Yanying
authors.initials: Y
authors.lastname: Xie
authors.forename: Qingqiang
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics; D036701:Limonins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D031586:Melia azedarach / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D004365:Drugs, Chinese Herbal; D036701:Limonins; C574807:methyl kulonate