[1]王 磊,刘红星,孙文利.HPLC-MS/MS法在骨髓移植患者他克莫司血药浓度测定中的应用[J].现代检验医学杂志,2017,32(02):126-130.[doi:10.3969/j.issn.1671-7414.2017.02.035]
　WANG Lei,LIU Hong-xing,SUN Wen-li.Application of HPLC-MS/MS Method in the Determination of Whole Blood Concentration of Tacrolimus in Bone Marrow Transplant Patient[J].Journal of Modern Laboratory Medicine,2017,32(02):126-130.[doi:10.3969/j.issn.1671-7414.2017.02.035]
点击复制

HPLC-MS/MS法在骨髓移植患者他克莫司血药浓度测定中的应用()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第32卷
期数:
2017年02期
页码:
126-130
栏目:
研究简报·实验技术
出版日期:
2017-03-25

文章信息/Info

Title:
Application of HPLC-MS/MS Method in the Determination of Whole Blood Concentration of Tacrolimus in Bone Marrow Transplant Patient
文章编号:
1671-7414(2017)02-126-05
作者:
王 磊; 刘红星; 孙文利
河北燕达陆道培医院,河北三河 065201
Author(s):
WANG Lei; LIU Hong-xing; SUN Wen-li
Hebei Yanda Lu·Daopei Hospital,Hebei Sanhe 065201,China
关键词:
FK506;  子囊霉素;  液相色谱-质谱联用技术;  治疗药物监测
分类号:
R617; Q503
DOI:
10.3969/j.issn.1671-7414.2017.02.035
文献标志码:
A
摘要:
目的 建立测定骨髓移植患者全血他克莫司(FK506)血药浓度的高效液相色谱-质谱联用(HPLC-MS/MS)法,探索HPLC-MS/MS法与羧基金属免疫分析(CMIA)法和化学发光微粒免疫(Elecsys)法在FK506血药浓度检测中的关系,为临床合理选用FK506血药浓度监测方法提供可靠依据。方法 采用子囊霉素作内标,全血样品经含内标甲醇沉淀蛋白处理。色谱柱为Ultimate XB-C18,柱温65℃,流动相为含0.1 g/dl甲酸和2 mmol/L乙酸铵的水和含0.1ml/dl甲酸的甲醇,梯度洗脱。质谱检测方式为电喷雾离子阱正离子模式,MRM扫描,监测FK506 m/z 821.5～768.5,子囊霉素m/z 809.4～756.4。选取部分骨髓移植患者全血FK506样本,分别用HPLC-MS/MS法,CMIA法和Elecsys法进行检测,对各种检测方法所检测的FK506浓度值进行比较。结果建立的HPLC-MS/MS法检测FK506血药浓度在0.5～50 ng/ml范围内线性关系良好,Y=0.228X-0.003 08(r=0.999 0)。HPLC-MS/MS法与CMIA法和Elecsys法检测FK506血药浓度结果相关性较好,差异无统计学意义。结论 建立了检测FK506血药浓度的HPLC-MS/MS法,该法可用于临床骨髓移植患者全血FK506浓度的监测。
Abstract:
Objective To develop a HPLC-MS/MS method for determination of Tacrolimus(FK506)in bone marrow transplant patient,and explorethe relationship of HPLC-MS/MS with CMIA and Elecsys in the measurement of FK506 blood drug concentration,and provide reliable basis for clinical rational use of monitoring method in FK506 blood drug concentration.Methods The separation was performed on a Ultimate XB-C18 column with amobile phase of water(containing 2 mmol/L ammonium acetate and 0.1 ml/dl formic acid)and methanol(containing 0.1 ml/dl formic acid).The way of eluting was gradient.Mass spectrum detection method was ESI positive ion mode and the MRMtransitions of FK506 m/z 821.5～768.5 and Ascomycin m/z 809.4～756.4.Selected part of the whole blood samples of FK506 in bone marrow transplant patient and respectively were tested by HPLC/MS/MS method,CMIA method and Elecsys method.Then,three methods for the detection of FK506 density were compared.Results The standard curve of FK506 was linear over the range of0.5～50 ng/ml,Y=0.228X-0.003 08(r=0.999 0).FK506 blood concentrationswere not significantly different in HPLC/MS/MS method,CMIA method and Elecsysmethod.Conclusion The HPLC-MS/MS method in the detection of FK506 was established and can be used for monitoring of whole blood concentration of FK506 in bone marrow transplant patients.

参考文献/References:

[1] Webb NJ, Roberts D, Preziosi R,et al.Fingerprick blood samples can be used to accurately measure tacrolimus levels by tandem mass spectrometry[J].Pediatric Transplantation,2005,9(6):729-733.
[2] Wang S,Magill JE,Vicente FB.A fast and simple high-performance liquid chromatography/mass spectrometry method for simultaneous measurement of whole blood tacrolimus and sirolimus[J].Archives of Pathology & Laboratory Medicine,2005,129(5):661-665.
[3] Poquette MA,Lensmeyer GL,Doran TC.Effective use of liquid chromatography-mass spectrometry(LC/MS)in the routine clinical laboratory for monitoring sirolimus,tacrolimus,and cyclosporine[J].Therapeutic Drug Monitoring,2005,27(2):144-150.
[4] Morris RG,Salm P,Taylor PJ,et al.Comparison of the reintroducedMEIA assay with HPLC-MS/MS for the determination of whole-blood sirolimus from transplant recipients[J].Therapeutic Drug Monitoring,2006,28(2):164-168.
[5] 王 磊,周枫叶,姜春菲,等.HPLC-MS/MS法测定白血病患者血浆伊马替尼与达沙替尼浓度[J].现代检验医学杂志,2016.31(1):128-131. Wang L,Zhou FY,Jiang CF,et al.Determination of imatinib and dasatinib in leukemia patients plasma by HPLC-MS/MS[J].Journal of Modern Laboratory Medicine,2016,31(1):128-131.
[6] 李 霞, 刘小红, 杨 乐.不同年龄阶段癫痫患儿奥卡西平活性代谢产物血药浓度的临床价值[J].现代检验医学杂志,2015,30(1):143-144,148. LI X,Liu XH,Yang L.Clinical values of blood serum concentration of MHD in children with epilepsy of different ages[J].Journal of Modern Laboratory Medicine,2015,30(1):143-144,148.
[7] 胡森安,艾红红,严丽花,等.维生素D及日照量对单纯性肥胖儿童血清瘦素水平影响的研究[J].现代检验医学杂志,2016,31(6):143-146. Hu SA,Ai HH,Yan LH,et al.Effect of vitamin D and sunlight on serum leptin levels in simple obese children[J].Journal of Modern Laboratory Medicine,2016,31(6):143-146.
[8] 邓安彦,蔡艳娟,周守容,等.ELISA法检测HBsAg(CMIA)低值血清样本的结果分析[J].现代检验医学杂志,2015,30(2):123-125. Deng AY,Cai YJ,Zhou SR,et al.Analysis of the results of ELISA bydetecting low quantitative HBsAg(CMIA)in serums[J].Journal of Modern Laboratory Medicine,2015,30(2):123-125.
[9] 刘立民,李 钰,蒙雨明,等.化学发光微粒免疫分析技术检测输血四项的性能评估[J].现代检验医学杂志,2015,30(2):107-110. Liu LM,Li Y,Meng YM,et al.Performance verification of chemiluminesent micropaticle immunoassay for the four blood index[J].Journal of ModernLaboratory Medicine,2015,30(2):107-110.
[10] Molinaro M,Regazzi MB,Pasquino S,et al.Pharmacokinetics of tacrolimus during the early phase after heart transplantation[J].Transplantation Proceedings,2001,33(3):2386-2389.
[11] Venkataramanan R,Shaw LM,Sarkozi L,et al.Cli-nical utility of monitoring tacrolimus blood concentrations in liver transplant patients[J].Journalof Clinical Pharmacology,2001,41(5):542-551.

备注/Memo

备注/Memo:

作者简介:王 磊(1984-),男,硕士,执业药师,主要从事医院药学研究工作,E-mail:rosie1982@163.com。
通讯作者:刘红星,男,硕士,执业医师,主要从事检验医学研究工作。
更新日期/Last Update: 2017-04-10