HPLC测定人血浆中霉酚酸及其代谢物浓度  被引量:4

Determination of Mycophenolic Acid and its Metabolins in Human Plasma by RP-HPLC

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作  者:赵强[1,2] 高峰 

机构地区:[1]山西医科大学公共卫生学院,太原030001 [2]解放军305医院,北京100017 [3]总参警卫局卫生保健处,北京100017

出  处:《中国现代应用药学》2010年第9期836-840,共5页Chinese Journal of Modern Applied Pharmacy

摘  要:目的建立反相高效液相色谱法,同时测定人血浆中霉酚酸(mycophenolic acid,MPA)、酚化葡萄糖醛麦考酚酸(phenol glucuronide metabolite,MPAG)、酰基化MPAG(acyl-MPAG,AcMPAG)的浓度。方法用蛋白沉淀法对样品进行处理。固定相为Zorbax Eclipse XDB C18柱(4.6 mm×250 mm,5μm),流动相:甲醇:20 mmol-L-1 NaH2PO4(用20%磷酸调至pH 3.0)为55∶45,流速:1.2 mL-min-1,检测波长:304 nm,柱温:45℃。结果 MPA、MPAG、AcMPAG浓度在0.2~50μg-mL-1(r=0.999 7)、2.8~531μg-mL-1(r=0.999 9)、0.3~24μg-mL-1(r=0.999 4)内呈良好的线性关系。MPA及其代谢物的绝对回收率均大于80%,MPA、MPAG、AcMPAG的相对回收率分别为94.0%~101.4%,98.4%~101.9%和96.1%~104.2%。日内及日间RSD远低于15%。结论采用反相高效液相色谱法测定人血浆中MPA、MPAG、AcMPAG的浓度和进行药物代谢动力学研究,方法灵敏度高、重复性强。OBJECTIVE RP-HPLC method detection for simultaneous determination of Mycophenolic acid(MPA),its phenol glucuronide metabolite(MPAG) and acyl-MPAG(AcMPAG) in human plasma was established.METHODS The plasma samples were prepared with protein-precipitating reagent,and the supernatant was eluted on Zorbax column(250 mm×4.6 mm,5 μm) with 20 mmol-L-1 NaH2PO4 buffer(pH 3.0,adjusted with 20% phosphoric acid) and methanol(45∶55) at 304 nm.The column temperature was 45 ℃,and the flow rate was 1.2 mL-min-1.RESULTS The assay was linear within the range of 0.2-50 μg-mL-1 for MPA(r=0.999 7),2.8-531 μg-mL-1 for MPAG(r=0.999 9),and 0.3-24 μg-mL-1 for AcMPAG(r=0.999 4).Mean absolute recovery of MPA and its metabolites was more than 80%.The average recoveries of MPA,MPAG and AcMPAG were 94%.0–101.4%,98.4%–101.9% and 96.1%–104.2 %,respectively.The RSD of within-day and between-day were all lower than 15%.CONCLUSION The method described is sensitive,reproducible,and will be useful in TDM or pharmacokinetic studies of MPA.

关 键 词:霉酚酸 酚化葡萄糖醛麦考酚酸 酰基化MPAG 反相高效液相色谱法 血浆浓度 

分 类 号:R969.11[医药卫生—药理学]

 

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