LC-MS/MS法测定犬血浆中阿莫西林的浓度及其药动学研究
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篇名: LC-MS/MS法测定犬血浆中阿莫西林的浓度及其药动学研究
TITLE:
摘要: 目的:建立测定犬血浆中阿莫西林浓度的方法,研究其药动学特征。方法:取12只比格犬,灌胃阿莫西林胶囊250 mg,分别于给药前和给药后0.5、1、1.5、2、2.5、3、3.5、4、4.5、5、5.5、6、8、10 h取血1.0~1.5 mL,以阿莫西林-d4为内标,血浆样品经酸性乙腈沉淀后,采用液相色谱-串联质谱法(LC-MS/MS)测定其中阿莫西林的血药浓度。色谱条件为色谱柱Waters Atlantis dC18,流动相乙腈(含0.1%甲酸)-10 mmol/L甲酸铵水溶液(pH 4.5),采用梯度洗脱的方式,流速0.3 mL/min,柱温30 ℃,进样量1 μL;质谱条件为电喷雾离子源,正离子模式,扫描方式为多反应监测,离子源喷雾电压5.5 kV,离子源温度450 ℃,雾化气压力30 psi,加热气压力40 psi,阿莫西林离子对m/z 366.2→113.9,内标离子对m/z 370.2→353.0,二者碎裂电压分别为26、16 V,驻留时间均为200 ms。结果:阿莫西林检测质量浓度在0.1~16 μg/mL范围内线性关系良好(r=0.998 2),日内、日间精密度的RSD分别小于14.3%、11.8%(n=5),准确度为93.0%~112.0%(n=3);提取回收率为58.9%~63.3%(RSD=3.3%,n=3),基质效应为2.8%(n=6),稳定性试验的RSD均小于15%(n=3)。阿莫西林在犬体内的药动学符合一室模型,t1/2为1.56 h、10 h内的药-时曲线下面积(AUC0-10 h)为24 300 ng·h/mL、cmax为7 523 ng/mL。结论:该方法灵敏、准确、简便、快速,可用于犬血浆中阿莫西林的血药浓度测定及药动学的研究。
ABSTRACT: OBJECTIVE: To develop the method for the determination of amoxicillin concentration in dog plasma, and to study its pharmacokinetic characteristics. METHODS: Totally 12 Beagle dogs were collected and given Amoxicillin capsules 250 mg intragastrically. The 1.0-1.5 mL plasma samples were collected before medication, and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10 h after medication. Using amoxicillin-d4 as internal standard (IS), after precipitated with acidic acetonitrile, the plasma concentration of amoxicillin was determined by LC-MS/MS. The separation was performed on an Atlantis dC18 column with mobile phase consisted of acetonitrile (containing 0.1% formic acid)-10 mmol/L ammonium formate water solution (pH 4.5, gradient elution) at the flow rate of 0.3 mL/min. The column temperature was 30 ℃, and sample size was 1 μL. Mass spectrum condition included ESI, positive ion mode, multiple reaction monitoring, ion source spray voltage 5.5 kV, ion source temperature 450 ℃, atomizing gas pressure 30 psi, heater pressure 40 psi, ion pair m/z 366.2→113.9 and m/z 370.2→353.0 for amoxicillin and IS, fragmentation voltage 26 and 16 V, residence time 200 ms. RESULTS: The linear range of amoxicillin was 0.1-16 μg/mL (r=0.998 2). RSDs of intra-day and inter-day were lower than 14.3% and 11.8% (n=5). The accuracy was 93.0%-112.0% (n=3). The extraction recoveries were 58.9%-63.3% (RSD=3.3%, n=3), and matrix effect was 2.8%(n=6). RSDs of stability test was lower than 15% (n=3). By single compartment model, the pharmacokinetic parameters of amoxicillin included that t1/2 was 1.56 h, AUC1-10 h was 24 300 ng·h/mL and cmax was 7 523 ng/mL. CONCLUSIONS: The method is sensitive, accurate, simple and rapid. It is applied for the determination of amoxicillin concentration in the plasma of dog and the pharmacokinetic study of amoxicillin.
期刊: 2018年第29卷第23期
作者: 张元元,王晨,张斗胜,周从亚,杨丽,赵荣生,翟所迪,张现化
AUTHORS: ZHANG Yuanyuan,WANG Chen,ZHANG Dousheng,ZHOU Congya,YANG Li,ZHAO Rongsheng,ZHAI Suodi,ZHANG Xianhua
关键字: 阿莫西林;液相色谱-串联质谱法;比格犬;血药浓度
KEYWORDS: Amoxicillin; LC-MS/MS; Beagle dog; Plasma concentration
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