异基因造血干细胞移植患者体内环孢素浓度测定及分析

目的：建立一种方便可行的环孢素A（ CsA）药物浓度测定方法，并对该院2012—2014年间异基因造血干细胞移植（ allo-HSCT）患者的CsA浓度监测结果加以分析，为临床使用CsA的有效性和安全性提供参考。方法采用高效液相色谱法（HPLC），血样经预处理后采用Ultimate XB－C18色谱柱分离；流动相为乙腈—水（85∶15）；流速1．2 mL· min－1；柱温65℃；检测波长λ＝214 nm。结果 CsA血药浓度在50～1000μg· L－1范围内，标准曲线线性关系良好（r＝0．9998），相对回收率为96．65％～101．82％，绝对回收率为91．78％～94．34％，日间及日内精密度RSD均小于4％。监测allo－HSCT患者共44例，其中23例CsA平均血药浓度在目标浓度范围内（200～400μg· L－1）；累计检测635例次，其中430例次在目标浓度范围内（200～400μg· L－1）。结论该方法方便、快速、可行，可用于临床CsA样本的测定。 allo－HSCT患者体内CsA浓度与发生移植物抗宿主病（GVHD）、药品不良反应（ADR）概率有相关性，平均血药浓度小于200μg· L－1的患者组更易发生移植物抗宿主病（ GVHD），而平均血药浓度大于400μg· L－1的患者组更易发生药物相关ADR反应，对allo－HSCT患者进行CsA浓度监测具有重要的临床意义。

Analyze and Monitor the Concentration of Cyclosporine Ain Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Objective To establish a convenient and feasible HPLC method for determination of cyclosporine A(CsA)level in blood and analyze the results of monitoring the concentration of cyclosporine A in the patients after allogeneic hematopoietic stem cell trans-plantation( allo-HSCT) in The First Affiliated Hospital Of Anhui Medical University from 2012 to 2014,which is used for studying the efficacy and safety in the clinic.Methods The CsA concentrations were determined with HPLC method,the blood samples was separa-ted with column Ultimate XB-C18;The mobile phase was a mixture of water and acetonitrile with the ratio of 15∶85.The flow rate was 1.2 mL· min-1 .The wave length of UV for detection was 214 nm and the column temperature was maintained at 65℃.Results A good line relationship was obtained within the blood CsA level range from 50μg· L-1 to 2 000μg· L-1 ( r=0.999 8) .The relative re-covery of CsA was 96.65%~101.82%and the absolute recovery of CsA was 91.78%~94.34%.The RSD was less than 4%.44 pa-tients and 635 samples with allo-HSCT were measured.Effective blood concentration(200 ~400 μg· L-1)was 23 patients and 430 samples.Conclusions The method is accurate,simple,sensitive and suitable for therapeutic monitoring of CsA.The concentration of CsA is related to the graft-versus-host disease( GVHD) and the adverse drug reaction( ADR). The patients whose average concentration less than 200μg· L-1 are more likely to get the GVHD and the patients whose average concentration more than 400μg· L-1 are more likely to get the ADR.It is important to monitor the concentration of CsA for the patients after allo-HSCT in the clinic.