title: LC-MS/MS determination of bakkenolide D in rats plasma and its application in pharmacokinetic studies.
abstract: A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of bakkenolide D (BD), which was further applied to assess the pharmacokinetics of BD. In the LC-MS/MS method, the multiple reaction monitoring mode was used and columbianadin was chosen as internal standard. The method was validated over the range of 1-800 ng/mL with a determination coefficient >0.999. The lower limit of quantification was 1 ng/mL in plasma. The intra- and inter-day accuracies for BD were 91-113 and 100-104%, respectively, and the inter-day precision was <15%. After a single oral dose of 10 mg/kg of BD, the mean peak plasma concentration of BD was 10.1 ± 9.8 ng/mL at 2 h. The area under the plasma concentration-time curve (AUC0-24 h ) was 72.1 ± 8.59 h ng/mL, and the elimination half-life (T1/2 ) was 11.8 ± 1.9 h. In case of intravenous administration of BD at a dosage of 1 mg/kg, the AUC0-24 h was 281 ± 98.4 h⋅ng/mL, and the T1/2 was 8.79 ± 0.63 h. Based on these results, the oral bioavailability of BD in rats at 10 mg/kg is 2.57%.
authors.affiliation: Key Laboratory for Molecular Design and Nutrition Engineering, Ningbo Institute of Technology, Zhejiang University, Ningbo 315100, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Dai
authors.forename: Lixia
authors.initials: L
authors.lastname: Pei
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D012717:Sesquiterpenes
keywords: LC-MS/MS; bakkenolide D; pharmacokinetics