治疗药物监测样本检测质量现状和标准化构想

Current status and standardization conception of the testing quality of therapeutic drug monitoring samples

准确测定患者体内药物浓度是做好治疗药物监测(TDM)工作,实施精准化药物治疗的必要前提,也是临床实验室的重要工作内容之一。TDM在免疫抑制剂(如环孢素A、他克莫司)、精神药物(如丙戊酸、卡马西平)和其他需要进行药物浓度监测的药物中都对临床治疗发挥着重要作用。用于TDM的血药浓度检测方法类别多,目前只有部分免疫学检测方法具备了经过批准的配套检测系统和试剂盒,但是大部分TDM项目的药物浓度检测方法属于高效液相色谱、液相色谱-串联质谱等技术,都是自建方法(LDT)。资料显示,同一检测项目不同检测方法之间的检测结果存在明显差异,同一方法不同实验室之间的检测结果也存在明显差异,究其原因,有以下几个方面:(1)TDM检测结果尚未实现量值溯源;(2)检测方法尚未实现标准化;(3)EQA计划的覆盖面不足;(4)TDM实验室参加EQA计划的意识不够;(5)TDM标准化尚处于初级阶段。这些问题制约了TDM的临床应用及相关研究工作的开展。为了解决这些问题,需要:(1)建立参考系统,实现检测结果量值溯源;(2)在逐步增加TDM EQA计划项目的同时,也要尽快开展正确度评价计划;(3)规范TDM样本检测技术;(4)加强实验室管理,建立完善的质量管理体系。

Accurate determination of drug concentration in blood samples is a necessary prerequisite for therapeutic drug monitoring(TDM)and the implementation of precise drug treatment,and it is also one of the important tasks of clinical laboratories.TDM plays an important role in clinical treatment in immunosuppressants(cyclosporine A,tacrolimus),psychotropic drugs(valproic acid,carbamazepine)and other drugs that require monitoring of drug concentration.There are many types of methods used for TDM for the detection of drug concentration in blood samples.At present,only a few immuno-assay methods were approved for marketing with detection systems and kits,most methods used for TDM are high performance liquid chromatography or liquid chromatography-tandem mass spectrometry which belong to laboratory developed tests(LDTs).Detection of TDM samples has many problems,such as incomparable testing results and large bias between different testing systems,including the biasbetween both different methods and different laboratories using the same method.There are several reasons:(1)the traceability chain has not been established,(2)the methods have not yet been standardized,(3)the coverage of the EQA plan is insufficient,(4)the awareness of TDM laboratories to participate in the EQA plan is insufficient,(5)TDM standardization is still in its infancy.These problems restrict the clinical application of TDM and the development of related research work.In order to solve these problems,it is necessary to:(1)Establish a reference system to realize the traceability of the test results;(2)While gradually increasing the TDM EQA plan items,the Trueness evaluation plan should be carried out as soon as possible;(3)Standardized TDM sample testing Technology;(4)Strengthen laboratory management and establish a complete quality management system.