摘要
目的建立玄麦甘桔颗粒中指标性成分甘草苷和哈巴俄苷在大鼠血浆中的超高效液相-质谱/质谱定量测定方法,并研究其体内药动学过程。方法色谱柱:菲罗门Kinetex C_(18)柱(50 mm×3 mm,2.6μm);柱温:20℃;流动相为0.1%甲酸(A)-乙腈(B);梯度洗脱;流速为0.3 mL/min;进样量:5μL。采用ESI源,多反应监测模式(MRM)负离子模式下检测各成分血药浓度。6只雄性大鼠灌胃玄麦甘桔颗粒药液后分别于给药后0.03、0.08、0.16、0.33、0.67、1、1.5、2、3、4、6、8、12 h,眼内眦取血0.5 mL测定血药浓度,并用DAS 3.0软件计算药动学参数。结果以芦丁为内标,甘草苷、哈巴俄苷的检测范围分别为0.78~50.0 ng/mL(r=0.997 9)和1.66~106.10 ng/mL(r=0.995 8)。方法回收率>82.3%,日内精密度与日间精密度RSD均<8.8%。甘草苷、哈巴俄苷大鼠体内的t_(1/2)分别为(3.46±2.08)、(3.28±1.17)h,C_(max)分别为(27.55±21.12)、(16.28±14.53)μg/L,t_(max)分别为(0.31±0.19)、(0.33±0.18)h,AUC_(0~12 h)分别为(48.82±11.35)、(64.85±46.70)μg·h/L。结论该方法快速、灵敏,重复性好,可用于玄麦甘桔颗粒2种指标性成分在大鼠体内的药代动力学研究。
Objective To establish a UPLC-MS/MS method for the determination of indicative components such as liquiritin and harpagoside in Xuanmai ganjie granules in rats＇ plasma,and to study the pharmacokinetics of them.Methods Phenomenex Kinetex C_（18） column（50 mm×3 mm,2.6μm） was used,and the column temperature was 20℃.The chromatography was eluted with mobile phase consisting of 0.1%formic acid solution（A） and acetonitrile（B） at the flow rate of 0.3 mL/min by gradient elution,the volume was 5μL.Multiple-reaction monitoring（MRM） scanning mode was employed for quantification with switching electrospray ion（ESI） source polarity in negative mode.Six SD male rats were docked to collect blood 0.5 mL from angular vein at 0.03,0.08,0.16,0.33,0.67,1,1.5,2,3,4,6,8 and 12 h after administration of Xuanmai ganjie granule solution to determine the blood concentration of drugs.The pharmacokinetic parameters were calculated by using DAS 3.0 software.Results The linear ranges of liquiritin and harpagoside were 0.78~50.00 ng/mL（r=0.997 9） and 1.66~106.10 ng/mL（r=0.995 8）,respectively.The intra-day RSD and inter-day RSD were all lower than 8.8%,and the average recoveries were more than82.3%.The pharmacokinetic parameters of liquiritin and harpagoside were as follows：t_（1/2）：（3.46 ± 2.08） and（3.28± 1.17） h,C_（max）：（27.55 ±21.12） and（16.28 ± 14.53）μg/L,t_（max）：（0.31 ±0.19） and（0.33 ±0.18） h,AUC_（0~12h）：（48.82 ± 11.35） and（64.85 ±46.70）μg·h/L.Conclusion The method is efficient,sensitive and reproducible,and can be used for pharmacokinetic analysis of liquiritin and harpagoside in vivo.
出处
《实用药物与临床》
CAS
2017年第3期318-321,共4页
Practical Pharmacy and Clinical Remedies
基金
河北省卫生厅青年科技课题(ZL20140340)
河北省中医药管理局指导性项目(2014152)
