Simultaneous determination of norisoboldine and its major metabolite in rat plasma by ultra-performance liquid chromatography-mass spectrometry and its application in a pharmacokinetic study.
Norisoboldine (NIB) is one of the main bioactive isoquinoline alkaloids in Linderae Radix. A rapid, selective and sensitive method using UPLC-ESI/MS was first developed for simultaneous determination of NIB and norisoboldine-9-O-α-glucuronide (NIB-Glu), its major metabolite in rat plasma. A one-step protein precipitation with methanol was employed as sample preparation technique. Chromatographic separation was carried out on an Acquity UPLC BEH C(18) column (50 × 2.1 mm, i.d. 1.7 µm) with a gradient mobile phase consisting of acetonitrile and water containing 0.1% formic acid. Detection and quantification were performed using a quadrupole mass spectrometer by selective ion reaction-monitoring mode. Good linearity was achieved using weighted (1/x(2) ) least squares linear regression over the concentration ranges 0.01-2 µg/mL for NIB and 0.025-25 µg/mL for NIB-Glu. The lower limit of quantification of NIB and NIB-Glu was 0.01 and 0.025 µg/mL, respectively. The intra- and inter-day precisions (relative standard deviations) of the assay at all three quality control levels were 4.6-14.1% for NIB, and 5.0-12.2% for NIB-Glu. The accuracies (relative error) were -13.5-8.1% for NIB and -12.8-7.6% for NIB-Glu, respectively. This developed method was successfully applied to an in vivo pharmacokinetic study in rats after a single intravenous dose of 10 mg/kg NIB.
MOE Key Laboratory for Standardization of Chinese Medicines and SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Jian-Zhong
JZ
Chen
Ying
Y
Xu
Gui-Xin
GX
Chou
Chang-Hong
CH
Wang
Li
L
Yang
Zheng-Tao
ZT
Wang
D000470:Alkaloids / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000470:Alkaloids; D020719:Glucuronides; C464745:norisoboldine