肾移植受者术后咪唑立宾血药浓度监测及肌酐清除率对其影响

发布时间：2018-10-24 13:45

【摘要】：目的:建立肾移植受者术后咪唑立宾浓度的高效液相色谱串联质谱(HPLC-MS/MS)分析方法,测定咪唑立宾浓度并探讨肌酐清除率对咪唑立宾血药浓度的影响。方法:HPLC色谱柱XDB-C18(150 mm×4.6 mm,5μm);流动相0.1%甲酸水溶液(A)-乙腈(B),梯度洗脱:0~2 min70%A,2~4 min40%A,4~7 min70%A;流速0.6 mL·min-1;电喷雾离子源ESI负离子模式。肾移植受者术后口服咪唑立宾(100 mg bid),在初次服药后第10日与第15日分别于服药前半小时和服药后3 h测定血药浓度,观察肌酐清除率对药物浓度的影响。结果:目标化合物咪唑立宾与内标BA-TPQ的离子质荷比(m/z)分别为258.2→126.1和278→91.1。二者分离完全,保留时间分别为2.14 min和2.74 min,提取回收率稳定,日内、日间精密度RSD低于15%,血浆样品在低温环境中稳定。肾移植受者血药浓度监测表明,咪唑立宾浓度与肌酐清除率高度相关,随肌酐清除率降低而升高,不良反应可能与峰浓度高有关。结论:肾移植术后监测咪唑立宾血药浓度,根据肌酐清除率调整给药剂量,有助于降低排异反应,减少不良反应的发生。
[Abstract]:Objective: to establish a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of midazolipin concentration in renal transplant recipients and to investigate the effect of creatinine clearance on the serum concentration of midazolipin. Methods: HPLC column XDB-C18 (150 mm 脳 4.6 mm,5 渭 m); mobile phase 0.1% formic acid solution (A) -acetonitrile (B), gradient elution: 0 ~ 2 min70%A,2~4 min40%A,4~7 min70%A; flow rate 0.6 mL min-1; electrospray ion source ESI negative ion mode). After renal transplantation, the serum concentrations of midazollibene were measured half an hour before and 3 hours after treatment at the 10th and 15th mg bid), after initial administration, and the effect of creatinine clearance on the drug concentration was observed. Results: the ion mass charge ratio (m / z) of the target compound imidolipin and internal standard BA-TPQ was 258.2 ~ 126.1 and 91.1 respectively. The separation was complete, the retention time was 2.14 min and the recovery rate of 2.74 min, was stable. The day precision RSD was lower than 15%, and the plasma sample was stable in low temperature environment. The monitoring of blood drug concentration in renal transplant recipients showed that the concentration of midazolbine was highly correlated with creatinine clearance and increased with the decrease of creatinine clearance, and the adverse reactions might be related to the high peak concentration. Conclusion: monitoring the blood concentration of midazolbine and adjusting the dosage according to the creatinine clearance rate after renal transplantation can help to reduce rejection reaction and decrease the occurrence of adverse reactions.
【作者单位】：首都医科大学附属北京友谊医院药学部;
【分类号】：R699.2

【相似文献】