Song Naining, Zhang Shaoyu, Li Quansheng, Liu Changxiao
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
J Pharm Biomed Anal. 2008 Nov 4;48(3):974-9. doi: 10.1016/j.jpba.2008.06.002. Epub 2008 Jun 11.
A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC/MS/MS) for the determination of tetrandrine in rat plasma has been developed, fully validated and successfully applied to pharmacokinetic study in Sprague-Dawley (SD) rats after a single oral administration. Sample preparation involves a liquid-liquid extraction with n-hexane-dichlormethane (65:35, containing 1% 2-propanol isopropyl alcohol, v/v). Tetrandrine and brodimoprim (internal standard) were well separated by LC with a Dikma C(18) column using acetonitrile-methanol-ammonium formate aqueous solution (20mM) containing 0.3% formic acid (20:30:50, v/v/v) as mobile phase. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 623.0-->381.0 and m/z 339.0-->281.0 for tetrandrine and I.S., respectively. The present method exhibited good linearity over the concentration range of 5-2,000 ng/mL for tetrandrine in rat plasma with a lower limit of quantification of 5 ng/mL. The intra- and inter-day precision were 2.0-9.2% and 4.5-9.4%, and the intra- and inter-day accuracy ranged from -7.6 to 10.3% and -6.0 to 5.3%, respectively. No endogenous compounds were found to interfere with the analysis, and tetrandrine was stable during the whole assay period. The method was successfully applied to a pharmacokinetic study after an intragastric administration (i.g.) of tetrandrine to SD rats with a single dose of 50mg/kg. The results confirm that the assay is suitable for the pharmacokinetic study of tetrandrine.
已建立一种快速、灵敏的液相色谱-串联质谱法（LC/MS/MS）用于测定大鼠血浆中的粉防己碱，该方法经过全面验证，并成功应用于对Sprague-Dawley（SD）大鼠单次口服给药后的药代动力学研究。样品制备包括用正己烷-二氯甲烷（65:35，含1%异丙醇，v/v）进行液-液萃取。使用迪马C(18)柱，以含0.3%甲酸（20:30:50，v/v/v）的乙腈-甲醇-甲酸铵水溶液（20mM）作为流动相，粉防己碱和溴地莫普明（内标）通过LC得到良好分离。在三重四极杆质谱仪上采用多反应监测模式进行检测。使用电喷雾电离（ESI(+)）对电离进行优化，并通过MS/MS分析实现选择性，粉防己碱和内标的m/z分别为623.0→381.0和339.0→281.0。本方法在大鼠血浆中粉防己碱浓度范围为5 - 2000 ng/mL时表现出良好的线性，定量下限为5 ng/mL。日内和日间精密度分别为2.0 - 9.2%和4.5 - 9.4%，日内和日间准确度分别在-7.6%至10.3%和-6.0%至5.3%之间。未发现内源性化合物干扰分析，且粉防己碱在整个分析期间稳定。该方法成功应用于对SD大鼠单次给予50mg/kg粉防己碱灌胃给药后的药代动力学研究。结果证实该测定方法适用于粉防己碱的药代动力学研究。
