Determination and pharmacokinetics of chinensinaphthol methyl ether in rat urine by a sensitive and specific UFLC-ESI-MS/MS method.
A rapid, stable, and sensitive method based on ultra-fast liquid chromatography combined with electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) was established and optimized for quantification and pharmacokinetics analysis of chinensinaphthol methyl ether (CME) in rat urine. Samples were prepared by liquid phase extraction with ethyl acetate, and chromatographic separation was performed on an ACQUITY UPLC(®) BEH Phenyl column (2.1×50mm, 1.7μm). For gradient elution, we used a mobile phase consisting of water containing 0.1% formic acid and 5mmol/L ammonium formate and methanol with 0.1% formic acid. The quantification was executed under multiple reaction monitoring (MRM) in positive mode. The precursor/product transition (m/z) in the positive ion mode was [M+H](+)m/z=395.1→346.1. This method was validated by evaluating specificity, linearity, matrix effects, recovery, accuracy, precision, and stability, which were all shown to be reasonable and reliable. The lower limit of quantification (LOQ) was 0.5ng/mL, and the linear range was 0.5-100ng/mL. The method was successfully applied to quantify and analyze the pharmacokinetics of CME in rat urine. After oral administration of a single dose of CME (5.0mg/kg), the accumulated amount of CME excreted in urine was 162.3±54.1ng, and the terminal elimination half-life was 53.4±5.3h, indicating low CME excretion in urine and significant CME metabolism in vivo.
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Jia'an
J
Qin
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Jiaoyang
J
Luo
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Hongzheng
H
Zhao
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Shanshan
S
Zhang
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: zxg332@126.com.
Xingguo
X
Zhang
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. Electronic address: yangmeihua15@hotmail.com.
Meihua
M
Yang
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008738:Methyl Ethers / Q000493:pharmacokinetics* / Q000652:urine*; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D008738:Methyl Ethers
Chinensinaphthol methyl ether; Determination; UFLC-ESI-MS/MS; Urine pharmacokinetics