Improvement On The Quality Control Level Of Therapeutic Drug Monitoring Of CsA

Objective:To observe the effects of storage temperature and storage time on monitoring whole blood concentration of CsA by FPIA;establish and improve the quality control(QC)method of therapeutic drug monitoring(TDM);and improve the QC level of monitoring blood concentration of CsA.Methods:Ten whole blood samples were collected from renal transplant recipients 12-hour after oral administration with CsA.Every sample was divided into two parts (A and B):While A group was stored at room temperature(25±4℃),B group was stored at cold-storage(6±2℃).The concentration of CsA was measured by FPIA after 6,24,72 hours respectively and the results were recorded.The stability of whole blood samples under different storage temperature and storage time was observed.20 batches of low,medium and high quality control samples of CsA were determined in 20 days continuously.Mean value was regarded as the target value and every control limit was confirmed with the multiple of the standard deviation(SD). The quality control graphs(Levey-Jennings QC graphs)and Z-score graphs were drawn by determination results of every batch of QC samples for monitoring drug blood concentration with improved Westgard multi-rule QC methods.Those graphs were used to judge it was "in control" or "out of control",and the results were analyzed and compared.Results:Relative standard deviation(RSD)of interday and intraday deviation of the low,medium and high quality control concentration were 2.28%,2.04%,2.14%,3.64%,3.02%and 2.91%in test precision respectively.The results accorded with the requirement for biological sample determination in the Chinese Pharmacopoeia, which should be less than 15%.The CsA whole blood samples were stored in different temperature,the test results showed that there was no significant statistic difference between samples stored at room temperature or at cold-storage for 72 hours(P＞0.05)with storage time prolonged.However,the results was P_A6＞P_A24＞P_A72,and P_B6＞P_B24＞P_B72,which showed that:storage in the same temperature, the longer the time,the greater the variance.That was the stability of the results was affected by storage time.The further statistic analysis showed that there was no statistic difference for samples stored at room temperature and Cold-storage for 24 hours(P＞0.05).So was it for 72 hours(P＞0.05).There was no statistic difference between the samples at different storage temperatures which were stored for the same time.The results were P_A24＜P_B24and P_A72＜P_B72for samples stored at same time, which showed that the variation for samples stored in cold-storage was less than those stored at room temperature.The accompanied QC determination results judged by constant QC scope were in control.There were 5 warnings and 1 "out of control" in the determination with improved Westgard multi-rules QC methods.RSDs of each tri-level parallel quality control results were 3.85%,4.89%,4.80%respectively.Conclusion:Whole blood sample of Cyclosporine A from renal transplant recipients can be stored at least for 72 hours at room temperature,and the determination results are credible.But they can be better at cold-storage.The quality control graphs (Levey-Jennings)and Z- score graphs are drawn with tri-level parallel(L,M,H) concentration of quality control samples.Tendency of quality control samples is monitored with improved Westgard multi-rule QC methods constantly,which can overcome the default without good uses of each determination results in constant QC scope and provide determination error of the lab truly.With the improved QC method it can improve the ability to test the error and decrease the appearance of false "out of control".So it ensures the stability and accuracy in monitoring blood concentration of CsA.