双黄连口服液黄芩苷、绿原酸、连翘酯苷A体内药代动力学研究
Research on An LC-MS Method for the Simultaneous Determination of Baicalin， Chlorogenic Acid and Forsythiaside A in Rat Plasma and its Application to Pharmacokinetic Study of Shuang-huang-lian in Rats
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摘要: 目的 建立同时测定双黄连口服液中黄芩苷、绿原酸、连翘酯苷A体内药代动力学过程。方法 血浆样品用混合溶剂提取（甲醇∶乙酸乙酯∶三氟乙酸=49∶48∶3），Hedera ODS 2（4.6 mm×250 mm，5 μm）分离，柱温30 ℃，流动相为乙腈-0.2%甲酸，流速为1.0 mL/min，电喷雾离子源(ESI)，SIM模式。检测离子：绿原酸，[M-H]-，m/z 353;黄芩苷，[M-H]-，m/z 445；连翘酯苷A，[M-H]-，m/z 623；灯盏乙素，[M-H]-，m/z 461。大鼠单剂量口服给药后，采用LC-MS法测定血浆中绿原酸、黄芩苷、连翘酯苷A浓度，Winnonlin 5.2软件对药-时曲线进行拟合，并计算药动学参数。结果 绿原酸在5~500 ng/mL，黄芩苷在10~2 000 ng/mL，连翘酯苷A在5~500 ng/mL线性关系良好（r≥0.991）；批内、批间精密度均小于15%；稳定性均在90.9%~103.1%范围内。方法学均已达到FDA生物药品分析要求。结论 该方法简便、准确、灵敏，可用于双黄连口服液体内药代动力学分析要求。Abstract: OBJECTIVE To establish the simultaneous determination of baicalin， chlorogenic acid and forsythiaside A in rat plasma and its application to pharmacokinetic study of Shuang-huang-lian in rats.METHODS Plasma samples were prepared with methanol-ethye acetate-trifluoroacetic acid (49∶48∶3) at a flow rate of 1.0 mL/min and detected with a mobile phase of acetonitrile-water containing 0.2% formic acid using ESI with negative ionization mode. Ions monitored in SIM mode were set as m/z 353[M-H]- for chlorogenic acid; m/z 445[M-H]- for baicalin; m/z 623[M-H]- for forsythiaside A. The concentration-time curves of baicalin， chlorogenic acid and forsythiaside A were simulated by Winnonlin5.2 and the pharmacokinetic parameters were calculated.RESULTS The calibration curve was linear within the range of 10~2 000 ng/mL for baicalin， 5~500 ng/mL for chlorogenic acid and forsythiaside A (r≥0.991). The RSDs of intra and inter day were all less than 15%， and the stability of baicalin， chlorogenic acid and forsythiaside A were controlled by the range of 90.9%~103.1%. The methods were all satisfied for the FDA level in analysis drug in vivo.CONCLUSION This method is simple， sensitive， and accurate， which can be used for analyzing Shuang-huang-lian in vivo.
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Key words:
- Shuang-huang-lian /
- baicalin /
- chlorogenic acid /
- forsythiaside A /
- pharmacokinetic
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