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中华临床实验室管理电子杂志

中华临床实验室管理电子杂志 ›› 2018, Vol. 06 ›› Issue (02) : 99 -103. doi: 10.3877/cma.j.issn.2095-5820.2018.02.007

所属专题： 文献；

实验研究

Elecsys与HPLC-MS/MS检测骨髓移植患者环孢素A血药浓度的相关性及其应用意义
王磊1, 孙文利1, 李培余1, 王红春1, 刘红星1,†()   
  1. 1. 065201　三河市，河北燕达陆道培医院临床药理室
  • 收稿日期:2018-01-22 出版日期:2018-05-28
  • 通信作者: 刘红星

Correlation of Elecsys and HPLC-MS/MS method in the determination of blood Cyclosporine A concentration in bone marrow transplant patients and its application

Lei Wang1, Wenli Sun1, Peiyu Li1, Hongchun Wang1, Hongxing Liu1,†()   

  1. 1. Department of Clinical Pharmacology, Hebei Yanda Ludaopei Hospital, Sanhe 065201, China
  • Received:2018-01-22 Published:2018-05-28
  • Corresponding author: Hongxing Liu
  • About author:
    Corresponding author: Liu Hongxing, Email:
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引用本文：

王磊, 孙文利, 李培余, 王红春, 刘红星. Elecsys与HPLC-MS/MS检测骨髓移植患者环孢素A血药浓度的相关性及其应用意义[J]. 中华临床实验室管理电子杂志, 2018, 06(02): 99-103.

Lei Wang, Wenli Sun, Peiyu Li, Hongchun Wang, Hongxing Liu. Correlation of Elecsys and HPLC-MS/MS method in the determination of blood Cyclosporine A concentration in bone marrow transplant patients and its application[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2018, 06(02): 99-103.

目的

探讨电化学发光(Elecsys)与液质联用(high performance liquid chromatography-tandem mass spectrometric，HPLC-MS/MS)检测骨髓移植患者环孢素A(Cyclosporin A，CSA)血药浓度的相关性，以建立两种方法更为准确合理的测定结果转换方法。

方法

用Elecsys和HPLC-MS/MS分别测定83例骨髓移植患者CSA谷浓度，采用线性回归分析、结果平均值，以及正态分布法对两种方法测定结果进行比较分析，以考察两种方法的相关性；然后，用3种数据处理方法进行加权残差分析，验证3种统计学方法的准确性。

结果

Elecsys与HPLC-MS/MS检测结果符合正态分布，测定CSA的平均值分别为139.2 ng/ml和149.7 ng/ml,且两种方法检测骨髓移植患者CSA血药浓度结果的差异均无统计学意义(t<0.01，P>0.05)。经线性回归分析(方程为Y=0.888X＋7.2696)，两种方法的相关性较好(r=0.999)；经3种数据分析方法所得换算系数分别为0.89、0.96和0.95。

结论

Elecsys与HPLC-MS/MS检测骨髓移植患者CSA血药浓度的结果相近，无需用系数换算，医生和临床药师可根据检测结果直接进行骨髓移植患者CSA个体化给药方案调整。

关键词: 电化学发光, 液质联用, 环孢素A, 血药浓度
Objective

To compare Elecsys and high performance liquid chromatographytandem mass spectrometric (HPLC-MS/MS) methods in measuring the blood Cyclosporine A (CSA) concentration of bone marrow transplant patients and to investigate the relationship of the results obtained from the two methods in order to establish a more accurate and reasonable conversion method.

Methods

The through concentration of CSA in 83 patients with bone marrow transplantation was measured by Elecsys and HPLC-MS/MS, respectively. The results from the two methods were analyzed by linear regression, and by the mean value and the normal distribution analyses in order to investigate the correlation of the two methods. Three data processing methods were performed to carry out weighted residual analysis and to verify the accuracy of the statistical methods.

Results

The mean concentrations of CSA were 139.2 ng/ml and 149.7 ng/ml measured by Elecsys and HPLC-MS/MS methods, respectively. There was no significant difference between Elecsys and HPLC-MS/MS in the determination of CSA concentration (t<0.01, P>0.05). The results obtained by the two methods were in accorded with normal distribution. Linear regression analysis showed that the correlation between the two methods was better (Y=0.888X+ 7.2696, r=0.999). The conversion coefficients obtained by the three data processing methods were 0.89, 0.96 and 0.95, respectively.

Conclusions

The results of the blood CSA concentration in bone marrow transplantation patients obtained by Elecsys and HPLC-MS/MS are similar., and the conversion coefficient of the two methods is not needed. Doctors and clinical pharmacists can directly adjust the individualized dosing of CSA in patients undergoing bone marrow transplantation according to the either testing results.

Key words: Elecsys, High performance liquid chromatographytandem mass spectrometric, Cyclosporin A, Blood concentration
图1 两种方法分别检测83例骨髓移植患者CSA血药浓度的5个批次的散点图
图2 Elecsys与HPLC-MS/MS检测83例骨髓移植患者CSA血浓度的相关性
图3 两种方法检测CSA谷浓度结果经对数转换后的频率分布直方图
表1 两种方法连续5日各测定20份标本结果的平均值分布(n=83)
检测日期 Elecsys(ng/ml) HPLC-MS/MS(ng/ml) Elecsys/HPLC-MS/MS比率 t值 P值
20151019 133.2 136.2 1.01 0.32 >0.05
20151020 167.6 183.9 0.92 0.67 >0.05
20151021 118.2 119.7 1.01 0.56 >0.05
20151022 129.0 138.8 0.94 <0.01 >0.05
20151023 132.0 144.6 0.92 <0.01 >0.05
合计 139.2 149.7 0.95 <0.01 >0.05
图4 两种方法测定骨髓移植患者CSA血浓度的比率一致性分析图
图5 83例骨髓移植患者CSA血药浓度3种统计分析方法的WRES分析散点图
1
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/CD]. 中华临床医师杂志：电子版, 2017,11(3):417-421.
2
王磊，刘红星，孙文利. HPLC-MS/MS法在骨髓移植患者全血CSA及AM1浓度测定中的应用[J]. 重庆医学, 2017,46(23):3234-3237.
3
梁晓丽，刘蕾，陈崸，等. HPLC-MS/MS和FPIA法测定全血中环孢素浓度的比较方法学[J]. 中国药学杂志, 2009,44(24):1904-1908.
4
Shimamoto T, Ohyashiki K. Immunosuppressive treatments for myelodysplastic syndromes[J]. Leuk Lymphoma, 2003,44(4):593-604.
5
黄金柱，罗晓，李咏，等. 肾移植术后抗感染治疗期间环孢素血药浓度监测与剂量调整[J]. 临床药物治疗杂志, 2015,13(4):81-84.
6
Passweg JR, Giagounidis AA, Simcock M, et al. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase Ⅲ trail comparing antithymocyte globulin plus cyclosporine with best supportive care-SAKK 33/99[J]. J Clin Oncol, 2011,29(3):303-309.
7
梁立艳，张莉，井丽萍，等. 环孢素血药浓度水平对重型再生障碍性贫血患者免疫抑制治疗近期疗效的影响[J]. 中华血液学杂志, 2011,32(11):766-771.
8
刘志艳，陈恳，刘园园，等. 伏立康唑对免疫抑制剂药代动力学影响的系统评价[J]. 临床药物治疗杂志, 2016,14(6):21-26.
9
Yamazaki H, Sugimori C, Chuhjo T, et al. Cyclosporine Therapy for Acquired Aplastic Anemia: Predictive Factors for the Response and Long-term Prognosis[J]. Int J Hematol, 2007, 85(3):186.
10
白薇，刘锋，李柳，等. 环孢素A治疗单纯红细胞再生障碍性贫血血药浓度与疗效关系探讨[J]. 临床血液学杂志, 2011,24(5):553-554.
11
Vogeser M, Shipkova M, Rigo-Bonnin R, et al. Multicenter Analytical Evaluation of the Automated Electrochemiluminescence Immunoassay for Cyclosporine[J]. Ther Drug Monit, 2014,36(5):640-650.
12
卫生部临床检验中心. 卫生部临床检验中心室间质量评价标准[S]. 北京：2017.
13
CLSI. Liquid Chromatography-mass spectrometry methods approved guideline[S]. CLSI document C62-A. Wayne. PA: CLSI, 2014.
14
中华医学会检验医学分会，国家卫生计划生育委员会，液相色谱-质谱临床应用建议[J]. 中华检验医学杂志, 2017,40(10):770-779.
15
European Medicines Agency. Guideline on validation of bioanalytical methods[S]. London: 2009.
16
Burlingame AL, Boyd RK, Gaskell SL. Mass spectrometry[J]. Anal Chem, 1994,66(12):634R-683R.
17
王磊，王红春，李培余, 等. 两种检测骨髓移植患者环孢素A血药浓度方法的比较[J/CD]. 中华临床实验室管理电子杂志, 2017,5(4):241-245.
18
陈文倩，刘晓，崔刚, 等. 对数正态分布在肾移植患者环孢素A谷浓度检测方法比较中的应用[J]. 中国药学杂志, 2014,49(4):329-333
19
朱愿超，梁良，赵明，等. 再生障碍性贫血患者环孢素Ａ血药浓度监测的回顾性分析[J]. 临床药物治疗杂志, 2015,13(5):20-24.
20
Andhavarapu S, Roy V. Immunomodulatory drugs in multiple myeloma[J]. Expert Rev Hematol, 2013,6(1):69-82.
21
Xiao Z, Xu Z, Zhang Y, et al. Cyclosporin A and thalidomide in patients with myelodysplastic syndromes: Results of a pilot study[J]. Leuk Res, 2011,35(1):61-65.
22
王翔岩，钟旭丽，宋泽亮，等. 儿童造血干细胞移植后环孢素A血药浓度监测[J]. 临床药物治疗杂志, 2015,13(6):21-24.
23
Saracco P, Quarello P, Iori AP, et al. Cyclosporine A response and dependence in children with acquired aplastic anaemia:a multicentre retrospective study with long-term observation follow up[J]. Br J Haematol, 2008,140(2):197-205.
24
中华医学会儿科学分会临床药理学组.儿童治疗性药物监测专家共识[J]. 中华儿科杂志, 2015,35(9):650-659.
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