丹红注射液对阿托伐他汀钙在大鼠体内药动学的影响
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篇名: | 丹红注射液对阿托伐他汀钙在大鼠体内药动学的影响 |
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摘要: | 目的:研究丹红注射液对阿托伐他汀钙(ATV)在大鼠体内药动学的影响。方法:以盐酸噻氯匹定为内标,采用超高效液相色谱-串联质谱法测定大鼠血浆中ATV的药物浓度。色谱柱为AcquityTM BEH C18,流动相为5 mmol/L甲酸铵溶液(含0.1%甲酸)-甲醇(梯度洗脱);离子源为电喷雾离子源,采用多反应离子监测(MRM)模式,质荷比(m/z)分别为559.20→440.20(ATV)、264.20→154.05(内标)。将24只SD大鼠随机分为ATV单用组(单独给予ATV,10 mg/kg)和丹红注射液低、中、高剂量联用组(给予丹红注射液1、2、4 mL/kg+ATV 10 mg/kg),分别于不同时间点取血,测定ATV血药浓度并计算其药动学参数。结果:ATV的血药浓度线性范围为0.25~62.50 ng/mL,定量下限为0.25 ng/mL;精密度、稳定性试验的RSD均小于15%;提取回收率、基质效应均大于85%。丹红注射液中、高剂量联用组ATV的cmax分别为(23.78±6.40)、(33.66±8.15)ng/mL,显著高于ATV单用组的(13.99±2.54)ng/mL(P<0.05);丹红注射液低、中、高剂量联用组ATV的AUC0-24 h分别为(67.20±15.22)、(88.16±14.84)、(126.84±31.55)ng·h/mL,显著高于ATV单用组的(46.08±7.47)ng·h/mL(P<0.05或P<0.01)。结论:丹红注射液联合给药可显著增加ATV在大鼠体内的暴露量。 |
ABSTRACT: | OBJECTIVE: To study the effects of Danhong injection on the pharmacokinetics of atorvastatin calcium (ATV) in rats. METHODS: The plasma concentration of ATV in rats was determined by UPLC-MS/MS using hydrochloric piperidine as internal standard. The determination was performed on AcquityTM BEH C18 column with mobile phase consisted of 5 mmol/L ammonium formate solution (containing 0.1% formic acid)-methanol (gradient elution). The ion source was ESI, and the mass transfer ratio (m/z) was 559.20→440.20 (ATV) and 264.20→154.05 (internal standard) by multiple reaction monitoring (MRM) mode. A total of 24 SD rats were randomly divided into ATV alone group (ATV, 10 mg/kg), Danhong injection low-dose, medium-dose and high-dose groups (Danhong injection 1, 2, 4 mL/kg+ATV 10 mg/kg). Blood samples were collected at different time points, and plasma concentration was determined and pharmacokinetic parameters of ATV were calculated. RESULTS: The linear range of ATV was 0.25-62.50 ng/mL, and the limit of quantitation was 0.25 ng/mL. RSDs of precision and stability tests were all lower than 15%. Extraction recovery and matrix effect were all higher than 85%. The pharmacokinetic parameter cmax of ATV in Danhong injection medium-dose and high-dose groups were (23.78±6.4), (33.66±8.15) ng/mL, which were significantly higher than (13.99±2.54) ng/mL in ATV alone group (P<0.05). AUC0-24 h of Danhong injection low-dose, medium-dose and high-dose groups were (67.20±15.22), (88.16±14.84), (126.84±31.55) ng·h/mL, which were significantly higher than (46.08±7.47) ng·h/mL in ATV alone group (P<0.05 or P<0.01). CONCLUSIONS: Combined administration of Danhong injection can significantly increase the plasma exposure of ATV in rats. |
期刊: | 2018年第29卷第24期 |
作者: | 朱金燕,彭灿,胡容峰,汤继辉,金涌 |
AUTHORS: | ZHU Jinyan,PENG Can,HU Rongfeng,TANG Jihui,JIN Yong |
关键字: | 阿托伐他汀钙;丹红注射液;药动学;联合用药;大鼠 |
KEYWORDS: | Atorvastatin calcium; Danhong injection; Pharmacokinetics; Combined administration; Rat |
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