化学发光微粒子免疫法和酶放大免疫法检测环孢素A全血浓度的相关性分析
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摘要
目的通过化学发光微粒子免疫法(CMIA)和酶放大免疫法(EMIT)检测环孢素A全血浓度,评价2种方法检测结果的准确性和相关性。方法 CMIA和EMIT检测低、中、高3个全血免疫抑制剂质控物,进行准确度和批内、批间精密度分析;已知浓度的环孢素A(49.5,155.2,395.8,500.0,995.0,1 390.1 ng·mL~(-1))加入到不含环孢素A全血样本中,检测后计算结果回收率;测定100份环孢素A患者全血样本,测定值用Deming法进行线性回归分析和Bland-Altman法计算偏倚。结果 CMIA低、中、高3个全血免疫抑制剂质控物准确度相对误差分别为5.8%,5.2%,9.1%,其批内和批间的变异系数分别为7.4%,6.9%,8.6%和10.1%,11.3%,8.7%,CMIA回收率分别为91%,95%,103%,102%,102%,104%;EMIT低、中、高3个全血免疫抑制剂质控物的相对误差分别为2.8%,2.3%,4.3%,其批内和批间的变异系数分别11.2%,5.9%,5.7%和11.3%,9.2%,8.3%,EMIT回收率分别为90%,92%,97%,98%,99%,102%;CMIA和EMIT平均差异偏倚21.7 ng·mL~(-1)(95%CI:-125.1～168.4 ng·mL~(-1)),EMIT测定值/CMIA测定值平均为0.951(95%CI:0.56～1.34),EMIT测定结果平均低于CMIA5%左右。结论 CMIA和EMIT检测环孢素A全血浓度符合免疫分析精密度的要求,2种方法的检测结果相关性好,临床合理调整用药剂量时应考虑检测方法类型不同造成的影响。
OBJECTIVE To assess the accuracy and correlation between chemiluminescent microparticle immunoassay(CMIA) and enzyme multiplied immunoassay technique(EMIT) in the determination of cyclosporine A(CSA)concentration in whole blood. METHODS The low, medium and high level of whole blood immunosuppressant control were determined by CMIA and EMIT, then the accuracy, intra-assay and inter-assay precision of each method were analyzed. The known concentrations of CSA(49.5, 155.2, 395.8, 500.0, 995.0 and 1 390.1 ng·ml~(-1)) were added into the whole blood sample without CSA and measured, then the recovery rates of testing results were calculated. Whole blood samples of 100 patients were detected, the results were analyzed by Deming regression for linear regression analysis and analyzed by Bland-Altman for calculating bias. RESULTS The relative error of the low, medium and high level of whole blood immunosuppressant control measured with CMIA was 5.8%, 5.2% and 9.1%, the intra-assay coefficient of variation(CV) was 7.4%, 6.9% and 8.6%, the inter-assay CV was 10.1%, 11.3% and 8.7%, and the recovery rate was 91%, 95%, 103%, 102%, 102% and 104%, respectively.While in EMIT, it was observed that the relative error was 2.8%, 2.3% and 4.3%, the intra-assay CV was 11.2%, 5.9% and 5.7%,the inter-assay CV was 11.3%, 9.2% and 8.3%, and the recovery rate was 90%, 92%, 97%, 98%, 99% and 102%, respectively.The bias of mean difference between CMIA and EMIT was 21.7 ng·mL~(-1)(95% CI: -125.1-168.4 ng·mL~(-1)). The relative value of EMIT/CMIA was 0.951(95% CI: 0.56-1.34). The determination results of EMIT was 5% lower than that of CMIA in average.CONCLUSION Determination of whole blood CSA concentration by CMIA and EMIT meet the requirement of accuracy in immune analysis. The results showed a good correlation between CMIA and EMIT. The effects of different types of detection methods should be taken into consideration for the rational dosage adjustment of drugs in clinic.
OBJECTIVE To assess the accuracy and correlation between chemiluminescent microparticle immunoassay(CMIA) and enzyme multiplied immunoassay technique(EMIT) in the determination of cyclosporine A(CSA)concentration in whole blood. METHODS The low, medium and high level of whole blood immunosuppressant control were determined by CMIA and EMIT, then the accuracy, intra-assay and inter-assay precision of each method were analyzed. The known concentrations of CSA(49.5, 155.2, 395.8, 500.0, 995.0 and 1 390.1 ng·ml~(-1)) were added into the whole blood sample without CSA and measured, then the recovery rates of testing results were calculated. Whole blood samples of 100 patients were detected, the results were analyzed by Deming regression for linear regression analysis and analyzed by Bland-Altman for calculating bias. RESULTS The relative error of the low, medium and high level of whole blood immunosuppressant control measured with CMIA was 5.8%, 5.2% and 9.1%, the intra-assay coefficient of variation(CV) was 7.4%, 6.9% and 8.6%, the inter-assay CV was 10.1%, 11.3% and 8.7%, and the recovery rate was 91%, 95%, 103%, 102%, 102% and 104%, respectively.While in EMIT, it was observed that the relative error was 2.8%, 2.3% and 4.3%, the intra-assay CV was 11.2%, 5.9% and 5.7%,the inter-assay CV was 11.3%, 9.2% and 8.3%, and the recovery rate was 90%, 92%, 97%, 98%, 99% and 102%, respectively.The bias of mean difference between CMIA and EMIT was 21.7 ng·mL~(-1)(95% CI: -125.1-168.4 ng·mL~(-1)). The relative value of EMIT/CMIA was 0.951(95% CI: 0.56-1.34). The determination results of EMIT was 5% lower than that of CMIA in average.CONCLUSION Determination of whole blood CSA concentration by CMIA and EMIT meet the requirement of accuracy in immune analysis. The results showed a good correlation between CMIA and EMIT. The effects of different types of detection methods should be taken into consideration for the rational dosage adjustment of drugs in clinic.
引文
[1]LI D Y,GE W H.Correlation study of PXR 1792A>G and1944T>C genotypes with the concentration/dose ratios of cyclosporine in renal transplantation subjects[J].Chin J Mod Appl Pharm(中国现代应用药学),2017,34(1):97-100.
[2]王艳,姬怀雪.环孢素A血药浓度监测注意事项及用药指导[J].临床合理用药,2012,5(32):171-172.
[3]陈新谦,金有豫,汤光.新编药物学[M].第17版.北京:人民卫生出版社,2011:691.
[4]王羽,乔小云,王璐璐,等.联合用药对环孢素A血浓度影响的研究进展[J].医药导报,2012,31(7):904-905.
[5]王欣晨,商玉萍.1236例次再生障碍性贫血患者环孢素A血药浓度与其肝肾毒性的相关性研究[J].中国药师,2017,20(3):513-515.
[6]WANG S M,LI P F,ZHAO X L,et al.LC-MS/MSdetermination of cyclosporine in human blood and application in pharmacokinetics[J].J Chin Mass Spect,2010,31(1):53-58.
[7]CHEN L,HE Q,RUAN J.Cyclosporine absorption profiling and therapeutic drug monitoring in stable renal allograft recipients[J].Chin J Mod Appl Pharm(中国现代应用药学),2010,27(5):466-468.
[8]廖秀娟,韦柳萍.环孢素A的药动学及其影响因素研究进展[J].中国药房,2015,26(4):558-560.
[9]JEBABLI N,KLOUZ A,BAHLOUS A,et al.Comparison of three methods for cyclosporine therapeutic monitoring[J].Transplant Proc,2007,39(8):2557-2559.
[10]JULIA M.Potter pharmaeoeeonomies of therapeutic drug monitoring in transplantation[J].Therapeut Drug Monitor,2000,22(4):361.
[11]陈璐,边原,涂碎萍,等.EMIT法和FPIA法监测全血环孢素A浓度相关性比较[J].国外医药抗菌药物分册,2017,38(1):41-43.
[12]王磊,孙文利,李培余,等.环孢素A血药浓度检测方法比较分析[J].中华临床医师杂志(电子版),2017,11(3):417-421.
[13]WILLEMZE A J,CREMERS S C,SCHOEMAKER R C,et al.Ciclosporin kinetics in children after stem cell transplantation[J].Br J Clin Pharmacol,2008,66(4):539-545.
[14]SCHULTZ K R,NEVILL T J,BALSHAW R F,et al.Effect of gastrointestinal inflammation and age on the pharmacokinetics of oral microemulsion cyclos porin A in the first month after bone marrow transplantation[J].Bone Marrow Transplant,2000,26(5):545-551.
[15]GRIVEAS I,VISVARDIS G,PAPADOPOULOU D,et al.Effect of cyclosporine therapy with low doses of corticosteroids on idiopathic nephritic syndro me[J].Artif Organs,2010,34(3):234-237.
[16]DUNCAN N,CRADDOCK C.Optimizing the use of cyelosporin in allogeneic stem cell transplantation[J].Bone Marrow Transplant,2006,38(3):169-174.
[17]WILLEMZE A J,CREMERS S C,SEHOEMAKER R C,et al.Ciclosporin kinetics in children after stem cell transplantation[J].Br J Clin Pharmacol,2008,66(4):539-545.
[18]VOLLENBROEKER B,KOEH J H,FOBKER M,et al.Determination of cyclosporine and its metabo-lites in blood via HPLC-MS and correlation to clinically Important parameters[J].Transplant Proc,2005,37(4):1741-1744.
[19]MAZA A,MONTAUDI H,SBIDIAN E,et a1.Oral eyclosporin in psoriasis:a systematic review on treatment modalities,risk of kidney toxicity and evidence for use in non-plaque psoriasis[J].J Eur Acad Dermatol Venereol,2011,25(Suppl 2):19-27.
[20]WANG L,LIU H X,SUN W L.The application of HPLC-MS/MS method in the determination of whole blood concentration of Cyclosporine A and AM1 in bone marrow transplant patient[J].Chongqing Med(重庆医学),2017,46(23):3234-3237.
[2]王艳,姬怀雪.环孢素A血药浓度监测注意事项及用药指导[J].临床合理用药,2012,5(32):171-172.
[3]陈新谦,金有豫,汤光.新编药物学[M].第17版.北京:人民卫生出版社,2011:691.
[4]王羽,乔小云,王璐璐,等.联合用药对环孢素A血浓度影响的研究进展[J].医药导报,2012,31(7):904-905.
[5]王欣晨,商玉萍.1236例次再生障碍性贫血患者环孢素A血药浓度与其肝肾毒性的相关性研究[J].中国药师,2017,20(3):513-515.
[6]WANG S M,LI P F,ZHAO X L,et al.LC-MS/MSdetermination of cyclosporine in human blood and application in pharmacokinetics[J].J Chin Mass Spect,2010,31(1):53-58.
[7]CHEN L,HE Q,RUAN J.Cyclosporine absorption profiling and therapeutic drug monitoring in stable renal allograft recipients[J].Chin J Mod Appl Pharm(中国现代应用药学),2010,27(5):466-468.
[8]廖秀娟,韦柳萍.环孢素A的药动学及其影响因素研究进展[J].中国药房,2015,26(4):558-560.
[9]JEBABLI N,KLOUZ A,BAHLOUS A,et al.Comparison of three methods for cyclosporine therapeutic monitoring[J].Transplant Proc,2007,39(8):2557-2559.
[10]JULIA M.Potter pharmaeoeeonomies of therapeutic drug monitoring in transplantation[J].Therapeut Drug Monitor,2000,22(4):361.
[11]陈璐,边原,涂碎萍,等.EMIT法和FPIA法监测全血环孢素A浓度相关性比较[J].国外医药抗菌药物分册,2017,38(1):41-43.
[12]王磊,孙文利,李培余,等.环孢素A血药浓度检测方法比较分析[J].中华临床医师杂志(电子版),2017,11(3):417-421.
[13]WILLEMZE A J,CREMERS S C,SCHOEMAKER R C,et al.Ciclosporin kinetics in children after stem cell transplantation[J].Br J Clin Pharmacol,2008,66(4):539-545.
[14]SCHULTZ K R,NEVILL T J,BALSHAW R F,et al.Effect of gastrointestinal inflammation and age on the pharmacokinetics of oral microemulsion cyclos porin A in the first month after bone marrow transplantation[J].Bone Marrow Transplant,2000,26(5):545-551.
[15]GRIVEAS I,VISVARDIS G,PAPADOPOULOU D,et al.Effect of cyclosporine therapy with low doses of corticosteroids on idiopathic nephritic syndro me[J].Artif Organs,2010,34(3):234-237.
[16]DUNCAN N,CRADDOCK C.Optimizing the use of cyelosporin in allogeneic stem cell transplantation[J].Bone Marrow Transplant,2006,38(3):169-174.
[17]WILLEMZE A J,CREMERS S C,SEHOEMAKER R C,et al.Ciclosporin kinetics in children after stem cell transplantation[J].Br J Clin Pharmacol,2008,66(4):539-545.
[18]VOLLENBROEKER B,KOEH J H,FOBKER M,et al.Determination of cyclosporine and its metabo-lites in blood via HPLC-MS and correlation to clinically Important parameters[J].Transplant Proc,2005,37(4):1741-1744.
[19]MAZA A,MONTAUDI H,SBIDIAN E,et a1.Oral eyclosporin in psoriasis:a systematic review on treatment modalities,risk of kidney toxicity and evidence for use in non-plaque psoriasis[J].J Eur Acad Dermatol Venereol,2011,25(Suppl 2):19-27.
[20]WANG L,LIU H X,SUN W L.The application of HPLC-MS/MS method in the determination of whole blood concentration of Cyclosporine A and AM1 in bone marrow transplant patient[J].Chongqing Med(重庆医学),2017,46(23):3234-3237.