UPLC法测定大鼠血浆中海南粗榧内酯醇及其药代动力学研究
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摘要
目的采用UPLC建立大鼠血浆中海南粗榧内酯醇浓度测定方法,并研究其经大鼠尾静脉注射给药后初步药代动力学。方法以甲醇-水(47∶53)为流动相,流速0.17 mL·min~(-1),UV检测波长326 nm,以海南粗榧内酯为内标,乙腈沉淀蛋白,测定给药后海南粗榧内酯醇在大鼠体内的浓度,由DAS2.1软件拟合药动学参数。结果海南粗榧内酯醇在0.05～10.0 mg·L~(-1)浓度范围内线性关系良好(r=0.999 6),日内和日间差异RSD均小于6%,提取回收率大于85%,方法学考察均符合要求。海南粗榧内酯醇按1、2、4 mg·kg~(-1)尾静脉给药后,在大鼠体内的半衰期T_(1/2)分别为(39.82±0.92)、(40.11±0.79)、(41.61±2.07)min,AUC_(0-t)为(65.77±1.08)、(130.48±1.26)、(268.75±1.24)min·mg·L~(-1)。结论该方法对海南粗榧内酯醇的专属性较强、快速方便、灵敏度较高,适合大批量生物样本分析。
Aim To establish a UPLC method for the determination of the concentration of hainanolidol in plasma of rats,and study the pharmacokinetics of hainanolidol in rat plasma after single dose i. v. administration of hainanolidol (1,2,4 mg·kg~(-1)). Methods The UPLC method for the determination of hainanolidol in rat plasma was established using hainanolide as internal standard. The mobile phase was methanol-water (47 ∶ 53),the flow rate was 0. 17 mL·min~(-1),and the detection wavelength was UV 326 nm. The plasma concentration of hainanolidol in rats was determined by UPLC after single-dose intravenous injection in rats with 1,2 and 4 mg · kg~(-1) of hainanolidol,and the pharmacokinetic parameters were calculated by DAS2. 1. Results The result of calibration curve was linear over the range of 0. 05 ~ 10. 00 mg · L~(-1) (r =0. 999 6). The lower limit of quantification was 0. 05 mg·L~(-1). The intra-day and inter-day precision were both lower than 5%,and the extraction recoveries were higher than 85%,respectively. The validated method was successfully applied to the pharmacokinetic study after i. v administration of hainanolidol in rats with doses of 1,2 and 4 mg·kg~(-1). The T_(1/2) was (39. 82 ±0. 92), (40. 11 ± 0. 79) and (41. 61 ± 2. 07) min,respectively. The AUC_(0-t) was (65. 77 ± 1. 08), (130. 48 ± 1. 26) and (268. 75 ± 1. 24) min·mg·L~(-1),respectively. Conclusion A simple and specific UPLC method for the analysis of hainanolidol is successfully developed,which could be applied to pharmacokinetic study in rat plasma.
Aim To establish a UPLC method for the determination of the concentration of hainanolidol in plasma of rats,and study the pharmacokinetics of hainanolidol in rat plasma after single dose i. v. administration of hainanolidol (1,2,4 mg·kg~(-1)). Methods The UPLC method for the determination of hainanolidol in rat plasma was established using hainanolide as internal standard. The mobile phase was methanol-water (47 ∶ 53),the flow rate was 0. 17 mL·min~(-1),and the detection wavelength was UV 326 nm. The plasma concentration of hainanolidol in rats was determined by UPLC after single-dose intravenous injection in rats with 1,2 and 4 mg · kg~(-1) of hainanolidol,and the pharmacokinetic parameters were calculated by DAS2. 1. Results The result of calibration curve was linear over the range of 0. 05 ~ 10. 00 mg · L~(-1) (r =0. 999 6). The lower limit of quantification was 0. 05 mg·L~(-1). The intra-day and inter-day precision were both lower than 5%,and the extraction recoveries were higher than 85%,respectively. The validated method was successfully applied to the pharmacokinetic study after i. v administration of hainanolidol in rats with doses of 1,2 and 4 mg·kg~(-1). The T_(1/2) was (39. 82 ±0. 92), (40. 11 ± 0. 79) and (41. 61 ± 2. 07) min,respectively. The AUC_(0-t) was (65. 77 ± 1. 08), (130. 48 ± 1. 26) and (268. 75 ± 1. 24) min·mg·L~(-1),respectively. Conclusion A simple and specific UPLC method for the analysis of hainanolidol is successfully developed,which could be applied to pharmacokinetic study in rat plasma.
引文
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[11]甘萍,霍仕霞,白鹏,等.类叶升麻苷在大鼠体内的药代动力学及组织分布研究[J].中国药理学通报,2014,30(3):417-20.[11]Gan P,Huo S X,Bai P,et al.Pharmacokinetics and tissue distribution of acteoside in rats[J].Chin Pharmacol Bull,2014,30(3):417-420.
[12]王晓钰,江小燕,于曦,等.升麻素在大鼠体内的药代动力学研究[J].中国药理学通报,2015,31(10):1443-6.[12]Wang X Y,Jiang X Y,Yu X,et al.Pharmacokinetic study on cimifugin in rats[J].Chin Pharmacol Bull,2015,31(10):1443-6.
[13]张敬茹,于小桐,孙宁,等.桑黄素和乙酰化白藜芦醇对沙奎那韦在大鼠体内药代动力学的影响[J].中国药理学通报,2017,33(10):1414-20.[13]Zhang J R,Yu X T,Sun N,et al.Effects of co-administration with morin and acetyl-resveratrol on pharmacokinetics of saquinavir in rats[J].Chin Pharmacol Bull,2017,33(10):1414-20.
[14]黄勇,胡杰,陆苑,等.UPLC-MS法测定大鼠血浆中荭草花的3个指标成分及其药动学研究[J].中国药理学通报,2015,31(9):1314-8.[14]Huang Y,Hu J,Lu Y,et al.Pharmacokinetics of three index components in flower of Polygonumorientale L.in rat plasma by UPLCMS[J].Chin Pharmacol Bull,2015,31(9):1314-8.
[2]梅文莉,吴娇,戴好富,等.三尖杉属植物化学成分与药理活性研究进展[J].中草药,2006,5(3):452-8.[2]Mei W L,Wu J,Dai H F,et al.Advances in studies on chemical constituents in plants of Cephalotaxus Sieb.et Zucc.and their pharmacological activities[J].Chin Herb Med,2006,5(3):452-8.
[3]孙南君,薛智,梁晓天,等.新抗癌有效成分海南粗榧内酯(Hainanolide)结构的研究[J].药学学报,1979,14(1):39-44.[3]Sun N J,Xue Z,Liang X T,et al.Study on the structure of anticancer active ingredient in harringtonolidol[J].Acta Pharm Sin,1979,14(1):39-44.
[4]薛智,孙南君,梁晓天.海南粗榧内酯醇的结构研究[J].药学学报,1982,17(3):236-7.[4]Xue Z,Sun N J,Liang X T.Study on the structure of harringtonolidol[J].Acta Pharm Sin,1982,17(3):236-7.
[5]O'Sullivan T P,Zhang H.Model studies toward the synthesis of the bioactive diterpenoid,harringtonolide[J].Org Biomol Chem,2007,5(2):2627-35.
[6]康淑卿,蔡胜勇,滕立.海南粗榧内酯的抗病毒作用[J].药学学报,1981,16(11):867-8.[6]Kang S Q,Cai S Y,Teng L.Antivirus effect of hainanolide[J].Acta Pharm Sin,1981,16(11):867-8.
[7]Zhang M,Liu N,Tang W.Stereoselective total synthesis of hainanolidol and harringtonolide via oxidopyrylium-based cycloaddition[J].J Am Chem Soc,2013,135(33):12434-8.
[8]张文江,周同惠.海南粗榧新碱衍生物HH07A在大鼠体内的代谢转化研究[J].药学学报,1998,33(3):212-6.[8]Zhang W J,Zhou T H.Study on metabolic transformation of the Hainanensine derivative HH07A in rats[J].Acta Pharm Sin,1998,33(3):212-6.
[9]王春,魏伟.芍药苷药物代谢动力学研究进展[J].中国药理学通报,2014,30(12):1646-50.[9]Wang C,Wei W.Research progress of pharmacokinetic study on paeoniflorin[J].Chin Pharmacol Bull,2014,30(12):1646-50.
[10]彭兆亮,汪电雷.HPLC测定大鼠血浆中1,8-二川芎嗪基大黄酸及其药代动力学研究[J].中国药理学通报,2016,32(1):109-13.[10]Peng Z L,Wang D L.Determination of 1,8-TMP rhein and its pharmacokinetics in rat plasma by HPLC[J].Chin Pharmacol Bull,2016,32(1):109-13.
[11]甘萍,霍仕霞,白鹏,等.类叶升麻苷在大鼠体内的药代动力学及组织分布研究[J].中国药理学通报,2014,30(3):417-20.[11]Gan P,Huo S X,Bai P,et al.Pharmacokinetics and tissue distribution of acteoside in rats[J].Chin Pharmacol Bull,2014,30(3):417-420.
[12]王晓钰,江小燕,于曦,等.升麻素在大鼠体内的药代动力学研究[J].中国药理学通报,2015,31(10):1443-6.[12]Wang X Y,Jiang X Y,Yu X,et al.Pharmacokinetic study on cimifugin in rats[J].Chin Pharmacol Bull,2015,31(10):1443-6.
[13]张敬茹,于小桐,孙宁,等.桑黄素和乙酰化白藜芦醇对沙奎那韦在大鼠体内药代动力学的影响[J].中国药理学通报,2017,33(10):1414-20.[13]Zhang J R,Yu X T,Sun N,et al.Effects of co-administration with morin and acetyl-resveratrol on pharmacokinetics of saquinavir in rats[J].Chin Pharmacol Bull,2017,33(10):1414-20.
[14]黄勇,胡杰,陆苑,等.UPLC-MS法测定大鼠血浆中荭草花的3个指标成分及其药动学研究[J].中国药理学通报,2015,31(9):1314-8.[14]Huang Y,Hu J,Lu Y,et al.Pharmacokinetics of three index components in flower of Polygonumorientale L.in rat plasma by UPLCMS[J].Chin Pharmacol Bull,2015,31(9):1314-8.