目的 建立腹膜透析液中万古霉素浓度测定的液相色谱-串联质谱法(LC-MS/MS)检测方法,考察腹膜透析相关性腹膜炎(PDAP)患者腹膜透析液(以下简称腹透液)和血清万古霉素浓度的相关性,以期为临床PDAP患者万古霉素腹腔给药和浓度监测提供参考。方法 采集我院18例PDAP患者万古霉素腹腔给药后(1 g,q4d~q6d)的腹透液样本,利用经方法学验证的LC-MS/MS方法测定腹透液万古霉素浓度,并通过Pearson相关性分析法进一步评价腹透液中药物浓度和血药浓度的关系。结果 建立的腹透液万古霉素LC-MS/MS测定方法在 0.1~16 μg·mL-1内线性关系良好,专属性、准确度、精密度等均符合要求。PDAP患者腹腔给与万古霉素后24、48、72、96和120 h的质量浓度分别为(5.99±3.33)、(4.08±2.13)、(3.40±1.23),(2.58±1.56)和(2.05±1.15)μg·mL-1;各时间点腹透液中药物浓度与血药浓度呈显著正相关关系。结论 建立的LC-MS/MS方法适用于临床腹透液样本的万古霉素检测,万古霉素血药浓度能够在一定程度上反映腹透液中药物浓度并指导临床合理用药。
Abstract
OBJECTIVE To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of vancomycin concentration in peritoneal dialysis solution in patients with peritoneal dialysis-associated peritonitis (PDAP), as well as to investigate the correlation between peritoneal dialysis and serum vancomycin concentrations, with the aim of providing a reference for peritoneal administration and therapeutic drug monitoring of vancomycin in clinical. METHODS Peritoneal dialysis solution samples were collected from 18 PDAP patients in our hospital with vancomycin intraperitoneal administration (1g, q4d-q6d). The concentration of vancomycin in peritoneal dialysis solution was determined using LC-MS/MS method after methodologically validation. The relationship between peritoneal dialysis and paired serum vancomycin concentration was further evaluated by Pearson correlation analysis. RESULTS The established LC-MS/MS method showed good linearity in the range of 0.1-16 μg/mL, and the specificity, accuracy and precision were all in accordance with the requirements. The peritoneal dialysis vancomycin concentrations at 24, 48, 72, 96 and 120 h after intraperitoneal administration in PDAP patients were (5.99±3.33), (4.08±2.13), (3.40±1.23), (2.58±1.56) and (2.05±1.15)μg·mL-1, respectively. There was a significant positive correlation between peritoneal dialysis and serum vancomycin concentration at all time points. CONCLUSIONT The developed LC-MS/MS method is suitable for the detection of vancomycin in peritoneal dialysis solution samples, and the vancomycin blood concentration can reflect the drug concentration in the abdominal cavity to a certain extent, which can help guide the rational clinical use of drugs.
关键词
万古霉素 /
腹膜透析相关性腹膜炎 /
腹膜透析液 /
液相色谱-串联质谱法 /
相关性分析
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Key words
vancomycin /
peritoneal dialysis-associated peritonitis /
peritoneal dialysis solution /
LC-MS/MS /
correlation analysis
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中图分类号：
R969.1
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参考文献
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脚注
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基金
国家临床重点专科( 临床药学) 建设项目资助;苏州市药物临床研究与个体化治疗重点实验室项目资助(SZS201719);苏州市科技局医疗卫生应用基础研究项目资助(SYSD2016146)
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