A Simple and Sensitive LC-MS/MS Method for Quantitation of Peimine and its Pharmacokinetic in Beagle Dogs

Abstract

A simple LC-MS/MS method was developed for determination and pharmacokinetic study of peimine in beagle dogs. The chromatographic separation was carried out on a Agilent Zobax SB C₁₈ column with a mobile phase consisting of acetonitrile-10 mmol/L ammonium formate (35:65, v/v) at a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by MRM via electro spray ionization source with positive mode. The standard curve for peimine was linear (r>0.999) over the concentration range of 1–200 ng/mL with a lower limit of quantification of 1 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 15% and the accuracy (relative error) was <5% at 3 quality control levels. This simple, fast and highly sensitive method was fully validated and successfully applied to a preclinical pharmacokinetic study of peimine in dogs after oral and intravenous administration.

Key words

peimine - LC-MS/MS - pharmacokinetics

• References

• 1 Li HJ, Jiang Y, Li P. Chemistry, bioactivity and geographical diversity of steroidal alkaloids from the Liliaceae family. Nat Prod Rep 2006; 23: 735-752
• 2 Yun YG, Jeon BH, Lee JH et al. Verticinone induces cell cycle arrest and apoptosis in immortalized and malignant human oral keratinocytes. Phytother Res 2008; 22: 416-423
• 3 Liu Z, Jin Y, Shen P et al. Separation and purification of verticine and verticinone from Bulbus Fritillariae Thunbergii by high-speed counter-current chromatography coupled with evaporative light scattering detection. Talanta 2007; 71: 1873-1876
• 4 Wu X, Chen J, Pan Y. Simultaneous determination of peimine and peiminine in rat plasma by LC-ESI-MS employing solid-phase extraction. Biomed Chromatogr 2010; 24: 902-907
• 5 Chen LH, Liu LL, Liu HN et al. Simultaneous determination of peimine and peiminine in rat plasma by LC-MS/MS and its application in the pharmacokinetic study. Yao Xue Xue Bao 2010; 45: 891-894
• 6 Xu FZ, Chen C, Zhang YH et al. Synthesis and antitussive evaluation of verticinone-cholic acid salt, a novel and potential cough therapeutic agent. Acta Pharmacol Sin 2007; 28: 1591-1596
• 7 Li SL, Lin G, Chan SW et al. Determination of the major isosteroidal alkaloids in bulbs of Fritillaria by high-performance liquid chromatography coupled with evaporative light scattering detection. J Chromatogr A 2001; 909: 207-214
• 8 Xue Y, Gu HL. Determination of peimine and peiminine in Fritillaria thunbergii by HPLC-ELSD. Yao Xue Xue Bao 2005; 40: 550-552
• 9 Liu Z, Jin Y, Shen P et al. Separation and purification of verticine and verticinone from Bulbus Fritillariae Thunbergii by high-speed counter-current chromatography coupled with evaporative light scattering detection. Talanta 2007; 71: 1873-1876
• 10 Xue Y, Wang F. Simultaneous determination of peimine, peiminine and zhebeinine in Fritillaria thunbergii from different habitat by HPLC-ELSD. Zhongguo Zhong Yao Za Zhi 2007; 32: 1628-1630
• 11 Xin GZ, Zhou JL, Qi LW et al. Turbulent-flow chromatography coupled on-line to fast high-performance liquid chromatography and mass spectrometry for simultaneous determination of verticine, verticinone and isoverticine in rat plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878: 435-441
• 12 http://www/fda.gov/cder/guidance/index.htm