前列安颗粒中芍药苷和连翘苷在大鼠体内的药动学研究
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篇名: | 前列安颗粒中芍药苷和连翘苷在大鼠体内的药动学研究 |
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摘要: | 目的:建立大鼠血浆中芍药苷和连翘苷浓度测定的方法,并用于大鼠ig前列安颗粒后的药动学研究。方法:采取液相色谱-质谱联用(LC-MS/MS)法。色谱柱为Waters C18;流动相为乙腈(A)-2 mmol/L乙酸铵溶液(含0.05%甲酸)(B)(0~9 min:15% A→50% A;9~11 min:50% A→90% A;11~17 min:90% A;17~19 min:90% A→15% A;19~20 min:15% A);流速为0.6 ml/min; 柱温为35 ℃;进样量为20 μl;定量离子对为芍药苷m/z 525.2→m/z 449.0,连翘苷m/z 552.3→m/z 355.3。7只雄性SD大鼠ig前列安颗粒药液1 g(生药)/kg后 0.25、0.5、0.75、1、1.5、2、3、4、6、8、10、12、24 h 眼内眦取血0.5 ml测定血药浓度,采用DAS 2.1.1药动学软件计算药动学参数。结果:芍药苷、连翘苷检测质量浓度线性范围分别为5.0~2 500.0 μg/L(r=0.997 9)、2.0~2 000.0 μg/L(r=0.998 2);精密度试验的RSD均小于5.5%(n=5);方法回收率分别为96.0%~104.0%、92.0%~107.0%,提取回收率分别为71.4%~83.5%、81.5%~92.3%;稳定性试验的RSD均小于5.0%(n=3)。芍药苷、连翘苷在大鼠体内的t1/2分别为(2.206±0.631)、(1.355±0.317) h,cmax分别为(1 504.069±620.885)、(79.043±15.568) μg/L,tmax分别为(1.000±0.250)、(1.214±0.267) h, AUC0-24 h分别为(4 897.645±2 207.577)、(263.475±54.795) μg·h/L,CL分别为(5.025±2.773)、(76.253±13.986) L/(h·kg)。结论:该方法灵敏度高、专属性强、操作简便、准确可靠,可应用于芍药苷、连翘苷在大鼠体内的药动学特征研究。 |
ABSTRACT: | OBJECTIVE: To establish a method for determining the plasma concentration of paeoniflorin and phillyrin and pharmacokinetic study before and after intragastric administration of Qianliean granules. METHODS: LC-MS/MS method was adopted. The column was Waters C18 with mobile phase consisted of acetonitrile (A)-2 mmol/L ammonium acetate (containing 0.05% formic acid)(B) (0-9 min:15% A→50% A;9-11 min:50% A→90% A;11-17 min:90% A;17-19 min:90% A→15% A;19-20 min:15% A), at the flow rate of 0.6 ml/min; column temperature was 35 ℃ and the volume was 20 μl; quantitative ions were paeoniflorin m/z 525.2 → m/z 449.0, phillyrin m/z 552.3 → m/z 355.3. 7 SD male rats were docked to collect blood 0.5 ml from angular vein 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h after administration Qianliean granule solution 1 g (medicinal materials)/kg to determine the blood concentration of drugs. DAS 2.1.1 software was employed to calculate pharmacokinetic parameters. RESULTS: The linear range of paeoniflorin and phillyri were 5.0-2 500.0 μg/L (r=0.997 9) and 2.0-2 000.0 μg/L (r=0.998 2), respectively; RSD of precision test was less than 5.5% (n=5); the method recovery were 96.0%-104.0% and 92.0%-107.0%, the extration recovery were 71.4%-83.5% and 81.5%-92.3% and RSD of stability test was less than 5.0% (n=3). The pharmacokinetic parameters of paeoniflorin and phillyrin were as follows as t1/2 of (2.206±0.631) and (1.355±0.317) h; cmax of (1 504.069±620.885) and (79.043±15.568) μg/L; tmax of (1.000±0.250) and (1.214±0.267) h; AUC0-24 h of (4 897.645±2 207.577) and (263.475±54.795) μg·h/L; CL of (5.025±2.773) and (76.253±13.986) L/(h·kg). CONCLUSIONS: The method is highly sensitive, exclusive, simple, accurate and reliable, and can be applied to study the pharmacokinetic characteristics of paeoniflorin and phillyrin in rats in vivo. |
期刊: | 2016年第27卷第10期 |
作者: | 田溪,梁振江,郭安然,杨秀岭 |
AUTHORS: | TIAN Xi,LIANG Zhenjiang,GUO Anran,YANG Xiuling |
关键字: | 液相色谱-质谱联用;前列安颗粒;连翘苷;芍药苷;药动学;大鼠 |
KEYWORDS: | LC-MS/MS; Qianliean granules; Phillyrin; Peoniflorin; Pharmacokinetics; Rats |
阅读数: | 262 次 |
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