Main content area

Developing an UPLC-MS/MS method to quantify maoecrystal A in rat plasma: Application to a pharmacokinetic study

Zhang, Chenning, Qin, Caibin, Yang, Guangyi, Boughaba, Fadia, He, Yue, Ma, Weidong, Zhang, Yonghong, Gao, Song
Journal of chromatography 2018 v.1086 pp. 105-109
Isodon (Lamiaceae), absorption, animal models, antibacterial properties, bioavailability, chromatography, diterpenoids, drugs, formic acid, freeze-thaw cycles, intravenous injection, medicinal properties, methanol, monitoring, pharmacokinetics, rats, spectrometers, tandem mass spectrometry
Maoecrystal A (MC-A) is an ent-kaurane-type diterpene isolated from Rabdosia eriocalyx (Dunn) Hara. MC-A has been reported to show different types of pharmacological activities, including anticancer, anti-inflammatory and bacteriostatic functions. However, bioanalysis of MC-A has not been reported. The purpose of this study is to develop an UPLC-MS/MS method to quantify MC-A in plasma and determine its pharmacokinetic properties using an animal model. The separation was performed using a Waters HSS T3 column (50 mm × 2.1 mm, 1.8 μm, Waters Corp., Milford, MA, USA) with methanol and water containing 0.1% of formic acid as the mobile phases. The mass analysis was performed in a Waters Xevo TQ mass spectrometer using multiple reaction monitoring (MRM) in positive scan mode. Protein precipitation was used to extract the drug from rat plasma samples. The calibration curve is linear in the concentration range 0.49–2000.0 ng/mL. The extraction recovery and the matrix effect were 78.11 to 91.72% and 90.38 to 98.02%, respectively. The RSD of inter/intra-day precisions were <13.72% and the accuracy was >86.41%. Stability studies showed that MC-A was stable (RSD < 14.98%) at different conditions (i.e., short-term, long-term, bench, and three freeze-thaw cycles) in rat plasma. The method was successfully applied to a pharmacokinetic study using rats through oral and intravenous administration routes. The oral bioavailability of MC-A was only 2.9%. Further studies are needed to determine the absorption and metabolism in order to improve the oral bioavailability of MC-A.