摘要
目的：建立快速测定肾脏移植血浆中麦考吗乙酯（Myeophenolate mofetil，MMF）活性代谢物霉酚酸（Mycophenolie acid，MPA）的高效液相色谱测定方法。方法：色谱条件为分析柱：Hypersil ODS2（4．6mm×200mm，5μm）；流动相：A相：25％乙腈＋75％0．02mol／L KH2PO4缓冲液（pH3．0），B相：70％乙腈＋30％0．02mol／L K2HPO4缓冲液（pH6．5）；梯度洗脱程序：0—14．5min为分析梯度，霉酚酸在8．7min出峰，继续用100％B流动相清洗4min。流速：1．0ml／min；检测波长254nm；柱温30℃；进样量100μl。9例肾脏移植患者13服MMF1．5g，不同时间采血，测定血浆中霉酚酸的浓度并计算药动学参数。结果：本方法线性范围为0．10—27mg／L时，峰面积与浓度呈良好的线性关系（r=0．9998），最低检出浓度为4μg／L，方法回收率分别为97．20％、98．73％和98．61％，日内精密度和日间精密度分别为3.5％、1.7％、0．6％和5．5％、3．0％、1．1％。药代动力学参数表明霉酚酸的平均血药浓度-时间曲线符合一室开放模型，tmax，ccma和AUC0-12h分别为0．94h、11．30mg／L和30．35mg·h·L^-1。结论：用高效液相色谱法梯度洗脱测定肾脏移植患者霉酚酸血药浓度，操作简便，结果准确。
Objective：To establish a quick HPLC method for determination of bioactive metabolite Mycophenolic acid（MPA） of M ycophenolate mofetil （MMF） in human plasma. Methods ：The chromatographic conditions include Hypersil ODS2 （4.6 mm × 200 mm,5 μm） ; mobile phase： gradient eluation of A[25% acetonitrile ＋ 75% 0.02 mol/L KH2PO4 buffer （pH3.0） ] -B [ 70% aectonitrile ＋ 30% 0. 02 mol/L K2HPO4 buffer（ pH 6.5） ] ,flow rate at 1.0 ml/min, wavelength 254 rim,column temperature was 30℃ and the dosage of MPA was 100 μl. The pharmacokinetic parameters of MPA taken by 9 patients showed standard curve in plasma. Results：The standard curve was linear（ r= 0. 9998） with the range of 0. 10 - 27 mg/L for MPA. The limit of detection in plasma was 4 μg/L. The average recovery was 97.20% , 98.73% and 98.61% , respectively. The intra day precision and inter day precision were 3.5%, 1.7% , 0.6% and 5.5% ,3.0%, 1.1% , respectively. The results showed that the pharmacokinetic of MPA was in accordance with the one compartment open model, tmax, cmax and AUC0 -12h was 0.94 h, 11.30 mg/L and 30.35 mg·h·L^-1, respectively. Conclusion ： The resolution, linearity, precision and average recovery of MPA can all meet the requirement of quantitative determination. The method is rapid,accurate and reliable.
出处
《华北国防医药》
2006年第6期388-390,共3页
Medical Journal of Beijing Military Region
关键词
肾移植
霉酚酸
麦考酚吗乙酯
色谱法
高效液相
Kidney transplant
Mycophelie acid
Mycophenolate mofctil
Chromatography, high performance liquid
