UPLC-MS/MS分析地榆皂苷Ⅱ在大鼠体内的药代动力学
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摘要
目的:通过超高效液相色谱-质谱联用法(UPLC-MS/MS)测定皮下注射地榆皂苷Ⅱ后大鼠体内血浆药物浓度,阐明地榆皂苷Ⅱ经皮下注射给药后在大鼠体内变化的动力学特征。方法:采用XTerraMS C18色谱柱(2.1 mm×50 mm,5μm),柱温30℃,流动相[0.1%甲酸水溶液-乙腈(9∶1,A)]-[乙腈-0.1%甲酸水溶液(9∶1,B)]梯度洗脱(0~1.5 min,10%B;1.5~2.0 min,10%~53%B;2.0~3.8 min,53%~62%B;3.8~4.1 min,62%~95%B;4.1~4.5 min,95%B;4.5~4.7 min,95%~10%B;4.7~6.0 min,10%B),流速0.4 m L·min-1,进样量2μL;电喷雾离子源(ESI),在多反应监测(MRM)负离子模式下测定血浆中地榆皂苷Ⅱ的血药浓度。结果:建立了地榆皂苷Ⅱ在大鼠血浆中质量浓度测定的方法,线性范围5~2 000μg·L-1(R2=0.997),测得皮下注射地榆皂苷Ⅱ后大鼠体内药物的药峰浓度(Cmax)(95.877±11.433)μg·L-1,半衰期(t1/2)(35.456±23.405)h,药时曲线下面积AUC_(0-24 h)(1 221.983±153.379)μg·h·L-1。结论:建立了一种能快速、准确、灵敏的测定大鼠血浆中地榆皂苷Ⅱ质量浓度的方法,可用于该类成分的血药浓度测定及药代动力学研究,为地榆皂苷的体内药动学研究和临床合理应用提供参考。
Objective: To clarify the pharmacokinetic characteristics of ziyuglycoside Ⅱ after subcutaneous injection by UPLC-MS/MS. Method: An XTerra MS C18 reversed phase column( 2. 1 mm ×50 mm,5 μm) was used for the determination of analyte. And mobile phase was consisted of [0. 1% formic acidacetonitrile( 9 ∶ 1) ]( A) and [acetonitrile-0. 1% formic acid( 9 ∶ 1) ]( B) for gradient elution( 0-1. 5 min,10% B; 1. 5-2. 0 min,10%-53% B; 2. 0-3. 8 min,53%-62% B; 3. 8-4. 1 min,62%-95% B; 4. 1-4. 5 min,95% B; 4. 5-4. 7 min,95%-10% B; 4. 7-6. 0 min,10% B),the flow rate was 0. 4 m L·min-1,the plasma concentration of ziyuglycoside Ⅱ was performed by negative ion mode in multiple reaction monitoring with electrospray ionization( ESI). Result: The method was successful established for determining the plasma concentration of ziyuglycoside Ⅱ in rats, its linear range was 5-2 000 μg·L-1( R2= 0. 997). The main pharmacokinetic parameters in rats after subcutaneous injection of ziyuglycoside Ⅱ suspension were obtained as follows: peak concentration( Cmax) of( 95. 877 ± 11. 433) μg·L-1,half-life period( t1/2) of( 35. 456 ±23. 405) h, area under curve( AUC0-24 h) of( 1 221. 983 ± 153. 379) μg·h·L-1. Conclusion: A rapid,accurate and sensitive method is established for determining plasma concentration of ziyuglycoside Ⅱ in rats,and it can be applied to determine plasma concentration and pharmacokinetic studies of this component. The study provides the pharmacokinetic evidence for the in vivo study and clinical rational medication.
Objective: To clarify the pharmacokinetic characteristics of ziyuglycoside Ⅱ after subcutaneous injection by UPLC-MS/MS. Method: An XTerra MS C18 reversed phase column( 2. 1 mm ×50 mm,5 μm) was used for the determination of analyte. And mobile phase was consisted of [0. 1% formic acidacetonitrile( 9 ∶ 1) ]( A) and [acetonitrile-0. 1% formic acid( 9 ∶ 1) ]( B) for gradient elution( 0-1. 5 min,10% B; 1. 5-2. 0 min,10%-53% B; 2. 0-3. 8 min,53%-62% B; 3. 8-4. 1 min,62%-95% B; 4. 1-4. 5 min,95% B; 4. 5-4. 7 min,95%-10% B; 4. 7-6. 0 min,10% B),the flow rate was 0. 4 m L·min-1,the plasma concentration of ziyuglycoside Ⅱ was performed by negative ion mode in multiple reaction monitoring with electrospray ionization( ESI). Result: The method was successful established for determining the plasma concentration of ziyuglycoside Ⅱ in rats, its linear range was 5-2 000 μg·L-1( R2= 0. 997). The main pharmacokinetic parameters in rats after subcutaneous injection of ziyuglycoside Ⅱ suspension were obtained as follows: peak concentration( Cmax) of( 95. 877 ± 11. 433) μg·L-1,half-life period( t1/2) of( 35. 456 ±23. 405) h, area under curve( AUC0-24 h) of( 1 221. 983 ± 153. 379) μg·h·L-1. Conclusion: A rapid,accurate and sensitive method is established for determining plasma concentration of ziyuglycoside Ⅱ in rats,and it can be applied to determine plasma concentration and pharmacokinetic studies of this component. The study provides the pharmacokinetic evidence for the in vivo study and clinical rational medication.
引文
[1]范奎,代良敏,伍振峰,等.放化疗所致骨髓抑制的研究进展[J].中华中医药杂志,2017,32(1):210-214.
[2]张洪印.术前放化疗在局部晚期结直肠癌患者中的应用及敏感性预测研究进展[J].中国普通外科杂志,2017,26(3):380-385.
[3]贾英杰,于建春,杨佩颖,等.中医药防治化疗致骨髓抑制的临床研究概况[J].辽宁中医杂志,2014,41(10):2253-2255.
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[6]代燕平,高小平,吴建明,等.地榆总皂苷对巨核祖细胞增殖分化及相关受体表达的影响[J].中国中药杂志,2014,39(9):1685-1689.
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[9]罗艳,王寒,原忠.地榆中三萜皂苷类成分及其抗炎活性研究[J].中国药物化学杂志,2008,18(2):138-141.
[10]郑子春,沈洪,朱萱萱,等.黄柏、地榆、白及对溃疡性结肠炎大鼠组织中NF-κB和细胞因子表达的影响[J].中国中医急症,2010,19(3):469-472.
[11]王菲,查清,王有胜.地榆升白片治疗妇科肿瘤化疗中白细胞减少症120例效果观察[J].山东医药,2010,50(43):94-95.
[12]张鹏天,王麦绒,张兆国,等.子宫肌瘤地榆粉介入栓塞治疗的临床观察[J].基层医学论坛,2015,19(22):3028-3030.
[13]代良敏,熊永爱,杨桂燕,等.地榆皂苷类成分对环磷酰胺致小鼠骨髓抑制的保护作用研究[J].天然产物研究与开发,2016,28(6):852-859.
[14]贾亮亮,奚炜,金桂兰.地榆升白片对环磷酰胺致小鼠骨髓抑制的拮抗作用[J].中国实验方剂学杂志,2012,18(18):251-254.
[15]王大光,佘万祥,郭宗云.地榆升白片治疗干扰素诱发白细胞减少症临床观察[J].山西中医,2014,30(12):33-33.
[16]李方方,李天宇,徐大明,等.地榆升白片治疗感染相关性中心粒细胞减少症疗效观察[J].中外医学研究,2013,11(23):189-189.
[17]李洁,侯甲福,李丽,等.小白花地榆总皂苷对环磷酰胺致小鼠白细胞减少症影响的研究[J].中国药物经济学,2015,7(1):13-14.
[18]高芸,王柯,朱雪,等.地榆皂苷Ⅰ诱导人甲状腺乳头状癌细胞BCPAP凋亡的实验研究[J].中国中西医结合杂志,2018,38(1):80-84.
[19]王振龙,何霞,成明,等.地榆皂苷Ⅱ抑制肿瘤细胞增殖和诱导其凋亡的作用[J].华西药学杂志,2017,32(5):485-488.
[20]YE W,FU H X,XIE L,et al.Development and validation of a quantification method for ziyuglycosideⅠandⅡin rat plasma:application to their pharmacokinetic studies[J].J Sep Sci,2015,38(13):2340-2347.
[2]张洪印.术前放化疗在局部晚期结直肠癌患者中的应用及敏感性预测研究进展[J].中国普通外科杂志,2017,26(3):380-385.
[3]贾英杰,于建春,杨佩颖,等.中医药防治化疗致骨髓抑制的临床研究概况[J].辽宁中医杂志,2014,41(10):2253-2255.
[4]岳秀永,付正丰.中医药治疗后骨髓抑制的研究概况[J].中国民族民间医药,2017,26(6):61-63.
[5]熊永爱,杨明.地榆鞣质与皂苷组分配伍对儿茶素、表儿茶素和地榆皂苷Ⅰ在大鼠体内药动学参数的影响[J].中国中药杂志,2016,41(19):3661-3667.
[6]代燕平,高小平,吴建明,等.地榆总皂苷对巨核祖细胞增殖分化及相关受体表达的影响[J].中国中药杂志,2014,39(9):1685-1689.
[7]代良敏,熊永爱,范奎,等.地榆化学成分与药理作用研究进展[J].中国实验方剂学杂志,2016,22(20):189-195.
[8]秦三海,李坤,周玲,等.地榆总皂苷抗肿瘤作用的实验研究[J].山东医药,2010,50(15):24-26.
[9]罗艳,王寒,原忠.地榆中三萜皂苷类成分及其抗炎活性研究[J].中国药物化学杂志,2008,18(2):138-141.
[10]郑子春,沈洪,朱萱萱,等.黄柏、地榆、白及对溃疡性结肠炎大鼠组织中NF-κB和细胞因子表达的影响[J].中国中医急症,2010,19(3):469-472.
[11]王菲,查清,王有胜.地榆升白片治疗妇科肿瘤化疗中白细胞减少症120例效果观察[J].山东医药,2010,50(43):94-95.
[12]张鹏天,王麦绒,张兆国,等.子宫肌瘤地榆粉介入栓塞治疗的临床观察[J].基层医学论坛,2015,19(22):3028-3030.
[13]代良敏,熊永爱,杨桂燕,等.地榆皂苷类成分对环磷酰胺致小鼠骨髓抑制的保护作用研究[J].天然产物研究与开发,2016,28(6):852-859.
[14]贾亮亮,奚炜,金桂兰.地榆升白片对环磷酰胺致小鼠骨髓抑制的拮抗作用[J].中国实验方剂学杂志,2012,18(18):251-254.
[15]王大光,佘万祥,郭宗云.地榆升白片治疗干扰素诱发白细胞减少症临床观察[J].山西中医,2014,30(12):33-33.
[16]李方方,李天宇,徐大明,等.地榆升白片治疗感染相关性中心粒细胞减少症疗效观察[J].中外医学研究,2013,11(23):189-189.
[17]李洁,侯甲福,李丽,等.小白花地榆总皂苷对环磷酰胺致小鼠白细胞减少症影响的研究[J].中国药物经济学,2015,7(1):13-14.
[18]高芸,王柯,朱雪,等.地榆皂苷Ⅰ诱导人甲状腺乳头状癌细胞BCPAP凋亡的实验研究[J].中国中西医结合杂志,2018,38(1):80-84.
[19]王振龙,何霞,成明,等.地榆皂苷Ⅱ抑制肿瘤细胞增殖和诱导其凋亡的作用[J].华西药学杂志,2017,32(5):485-488.
[20]YE W,FU H X,XIE L,et al.Development and validation of a quantification method for ziyuglycosideⅠandⅡin rat plasma:application to their pharmacokinetic studies[J].J Sep Sci,2015,38(13):2340-2347.