去甲万古霉素血药浓度检测方法的建立及评价

去甲万古霉素是我国研制生产的糖肽类抗生素，其化学结构、药理性质和抗菌作用与万古霉素相似，但治疗成本明显低于万古霉素。由于万古霉素与去甲万古霉素对耐药金黄色葡萄糖球菌和表皮葡萄球菌感染有很好的疗效，且不易诱导细菌产生耐药性，因此深受临床重视，实际应用中常需监测血药浓度。测定万古霉素血药浓度的方法主要为高效液相色谱法和免疫法。采用高效液相色谱法检测去甲万古霉素血药浓度灵敏度高、专一性好，但样本处理方法复杂且测量速度慢，不符合医院监测血药浓度的实际情况，而目前市场上没有专门针对去甲万古霉素开发的检测试剂盒。因此研究一种适用于医疗机构的去甲万古霉素血药浓度的方法十分必要。我院目前使用的血药浓度检测仪器为德国西门子公司的Viva-E血药浓度分析系统，检测方法为酶放大免疫法（enzyme- multiplied immunoassay technique，EMIT），检测原理是基于抗原（万古霉素）与酶标抗原竞争抗体从而由酶活力反映抗原浓度。目前临床常用的糖肽类抗菌药物有万古霉素、去甲万古霉素、替考拉宁，均具有

去甲万古霉素血药浓度检测方法的建立及评价

董　迪，毛　璐，宋　菲，张　威，甄健存（北京积水潭医院，北京 100035）

[摘要]　目的：建立适用于临床应用的去甲万古霉素血药浓度检测方法，为临床合理用药提供治疗药物监测手段。方法：应用酶放大免疫法检测去甲万古霉素血药浓度，对日间差、定量下限等项目进行初步研究，并与高效液相色谱法测定结果进行对比。结果：去甲万古霉素对市售酶放大免疫法万古霉素检测试剂响应良好，利用此法建立的检测方法测得结果日内（各测试组CV均小于15%）、日间差（P = 0.603 9）在药典要求范围内，与高效液相色谱法测得结果无显著性差异（P值分别为0.467 8、0.342 0），初步建议检测下限应≥ 3.0 μg·mL-1。结论：酶放大免疫法适用于医疗机构检测患者去甲万古霉素血药浓度，提示可利用免疫法试剂盒的交叉反应检测抗原结构类似物。去甲万古霉素血药浓度不同检测方法间的差异有待更进一步的研究。临床需要更多去甲万古霉素药代/药效动力学数据指导用药，以保障患者用药安全。

[关键词]　去甲万古霉素；治疗药物监测；血药浓度；酶放大免疫法

[中图分类号]　R917 [文献标识码]　A [文章编号]　1672 – 8157(2019)03 – 0146 – 04 Establishment and evaluation of a method for norvancomycin concentration determination in human plasma DONG Di, MAO Lu, SONG Fei, ZHANG Wei, ZHEN Jian-cun(Beijing Jishuitan Hospital, Beijing 100035, China) [ABSTRACT]　Objective:To establish a method for monitoring the plasma concentration of norvancomycin in order to provide therapeutic drug monitoring method for clinical rational drug use. Methods:Enzyme-multiplied immunoassay technique

(EMIT) was adopted to detect plasma concentration of norvancomycin. Test items such as between-day variances and lower limit of quantitation obtained by EMIT were studied preliminarily and compared with those of high performance liquid chromatography (HPLC). Results:Norvancomycin samples had a good response to vancomycin test kit by EMIT on market. The within-day variances (the CV of each test group was less than 15%) and between-day variances (P = 0.603 9) of the results detected by EMIT were all within the requirement range of Chinese pharmacopoeia, which had no significant difference compared with those of HPLC (P values were 0.467 8 and 0.342 0 respectively). A preliminary recommended lower detection limit was more than 3.0 μg·mL-1. Conclusion: EMIT was suitable for the detection of norvancomycin plasma concentration in medical institution, which indicated that antigen structural analogues could be detected by the immune cross reaction in immunoassay kit. The variance between different detection methods of norvancomycin need further study. More data about pharmacokinetics/pharmacodynamics of norvancomycin were required to guide drug use and ensure the medication safety of patients.

[KEY WORDS]　Norvancomycin; Therapeutic drug monitoring; Plasma concentration; Enzyme-multiplied immunoassay technique

[基金项目]　北京市属医院科研培育项目（PX2017054）

[通信作者]　甄健存，女，主任药师，研究方向：医院药事管理、

药物经济学、临床药学。E-mail：zhenjiancun@

[作者简介]　董迪，男，主管药师，研究方向：医院药学。E-mail：

jstdongdi@