目的 建立同时测定人血浆中吗啡、羟考酮、哌替啶及芬太尼4种治疗药物浓度的方法,并用于治疗药物的监测。方法 血浆样本经乙腈沉淀蛋白后,以氘代吗啡作为内标,应用超高效液相色谱-串联质谱法(UPLC-MS/MS)测定药物浓度。以Agilent Eclipse XDB-C18柱(2.1 mm ×50.0 mm, 1.7 μm)为色谱柱,甲醇-水(2.0 mmol·L-1醋酸铵)为流动相等度洗脱,流速为0.3 mL·min-1,电喷雾离子源,应用多重反应监测模式进行正离子扫描分析。结果 吗啡、羟考酮、哌替啶及芬太尼的血药浓度在50.0～10 000.0 ng·mL-1内线性关系良好,日内及日间精密度均小于15.0%,提取回收率及基质效应均在85.0%～115.0%内,稳定性等符合要求。结论 该方法灵敏、快速、专属性强,可以用于吗啡、羟考酮、哌替啶及芬太尼治疗药物浓度监测及药动学等方面的研究。
Abstract
OBJECTIVE To establish a UPLC-MS/MS method to simultaneously determine the concentrations of morphine, oxycodone, pethidine and fentanyl in human plasma for therapeutic drug monitoring(TDM). METHODS Morphine-D3 was used as the isotope internal standard. The analytes were extracted from plasma by using acetonitrile and separated using an Agilent Eclipse XDB-C18 column(2.1×50 mm,1.7 μm) with water containing 2 mmol·L-1 ammonium acetate and methanol as the mobile phase. The flow rate was 0.3 mL·min-1. With positive ion electrospray ionization, the analytes were monitored on a triple quadrupole mass spectrometer in MRM mode. RESULTS Calibration curves were obtained over the concentration ranges of 50.0-10 000.0 ng·mL-1 for all the analytes, and the intra-and inter-day precision RSDs were <15.0%. The recovery and matrix effect were within the range of 85.0% to 115.0%. Stability was in line with relevant requirements. CONCLUSION The method is proved to be sensitive, rapid, and can be used for TDM and pharmacokinetic studies of morphine, oxycodone, pethidine, and fentanyl.
关键词
超高效液相色谱串联质谱 /
方法学验证 /
镇痛药物 /
血浆药物浓度 /
治疗药物监测
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Key words
UPLC-MS/MS /
method validation /
analgesics /
plasma drug concentration /
therapeutic drug monitoring
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中图分类号：
R917
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