目的 建立液相色谱串联质谱法测定早产儿咖啡因血清浓度的方法,并对66例早产儿给药7 d后的咖啡因血清谷浓度进行监测及疗效评估。方法 采用咪达唑仑作为内标,样品经过蛋白沉淀法处理后上样。色谱柱为UPLC BEH C18(2.1 mm×50 mm,1.7 μm),柱温设为30 ℃,流动相由甲醇和0.1％甲酸组成,梯度洗脱,流速为0.4 mL·min-1,洗脱时间为4 min,进样量10 μL。收集连续使用咖啡因7 d后早产儿血清,进行咖啡因血清谷浓度测定,并观察患儿在用药第8~12天疗效和不良反应发生情况。结果 血清中内源性物质不干扰待测物定量,咖啡因血清浓度在0.5~64 μg·mL-1内呈良好的线性关系(R2为0.999 5)。66例早产儿给药7 d后咖啡因血清浓度为(8.92±6.31) μg·mL-1,治疗有效率和不良反应发生率分别为68.18%和10.60%。咖啡因血清浓度水平与治疗有效率和不良反应发生率均有一定的关系,具有统计学意义(P值分别为0.033和0.011)。结论 本方法灵敏度高,重复性好,所需样本量少,能快速准确测定咖啡因血清浓度,为临床安全有效使用咖啡因治疗早产儿呼吸暂停提供保障和依据。
Abstract
OBJECTIVE To establish a LC-MS/MS method for determination the serum caffeine concentration in 66 preterm infants after 7 days of continuous use of caffeine and evaluate the effectiveness. METHODS Midazolam was used as internal standardand samples were processed by protein precipitation method. The determination was performed on UPLC BEH C18 column(2.1 mm×50 mm, 1.7 μm) at 30 ℃. The mixture of methanol and 0.1% formic acid was used as the mobile phase. The flow rate was 0.4 mL·min-1 with the elution time 4 min, and injection volume was 10 μL. Serum of preterm infants were collected after 7 days of continuous administration of caffeine, and the serum valley concentration of caffeine was determined. The effectiveness and the incidence of adverse reactions were observed at 8-12 days after administration of caffeine. RESULTS Endogenous substances in serum did not interfere with the quantification of the substances to be measured, and the calibration range of caffeine was 0.5-64 μg·mL-1(R2=0.999 5). The caffeine serum concentration of 66 preterm infants after 7 days of administration were 8.92±6.31 μg·mL-1, and the effective rate and adverse reaction rate were 68.18% and 10.60%, respectively.Caffeine serum concentration level was significantly correlated with the effective rate and adverse reaction rate(P value was 0.033 and 0.011, respectively). CONCLUSION This method has the advantages of high sensitivity, good reproducibility and small sample size, and can quickly and accurately determine the serum concentration of caffeine, which provides a guarantee and basis for the safe and effective use of caffeine in clinical treatment of premature infants with apnea.
关键词
咖啡因 /
血清浓度 /
早产儿 /
液相色谱串联质谱法 /
疗效
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Key words
caffeine /
serum concentration /
premature infant /
LC-MS/MS /
effectiveness
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中图分类号：
R969
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参考文献
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脚注
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基金
宁波市自然科学基金项目资助(2018A610245);浙江省药学会医院药学专项科研项目资助(2018ZYY37);浙江省医药卫生项目资助(2020KY279)
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