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UPLC-MS/MS法测定人血浆中伏立康唑的浓度及其临床应用
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| 篇名： | UPLC-MS/MS法测定人血浆中伏立康唑的浓度及其临床应用 |
| TITLE： | |
| 摘要： | 目的：建立测定人血浆中伏立康唑浓度的方法，并应用于临床。方法：采用超高效液相色谱-串联质谱法测定。以酮康唑为内标，色谱柱为Shim-pack VP-ODS，流动相为水（含1‰甲酸及2 mmol/L乙酸铵）-乙腈，梯度洗脱，流速为0.3 ml/min，柱温为40 ℃；采用电喷雾离子源，以多反应监测方式进行正离子扫描，用于定量分析的离子对分别为m/z 351.2→282.2（伏立康唑）、m/z 532.1→490.2（内标）。结果： 伏立康唑血药浓度在1～10 000 ng/ml范围内线性关系良好（r＝0.999 5，n＝5），定量下限为1 ng/ml；日内、日间RSD＜10％；方法回收率＞90％（RSD＜8％），提取回收率＞70％（RSD＜8％）。采用该法检测10例深部真菌感染患者体内伏立康唑的血药浓度为507.33～7 011.24 ng/ml，有3例患者的血药浓度不在推荐治疗浓度范围内。结论：该方法快速、准确、灵敏度高，适用于伏立康唑治疗药物监测。 |
| ABSTRACT： | OBJECTIVE： To develop a method for concentration determination of voriconazole in human plasma and apply it in the clinic. METHODS： UPLC-MS/MS method was adopted. Using ketoconazole as internal standard， the determination was performed on Shim-pack VP-ODS column with mobile phase consisted of water （containing 1‰ formic acid and 2 mmol/L ammonium acetate）-acetonitrile （gradient elution） at flow rate of 0.3 ml/min and column temperature of 40 ℃.The electrospray ion source， positive ionizing pattern and multiple reaction monitoring were used； the mass transition ion-pairs of voriconazole and internal standard were m/z 351.2→282.2 and m/z 532.1→490.2. RESULTS： The linear range of voriconazole were 1-10 000 ng/ml （r＝0.999 5， n＝5）， and the limit of quantitation was 1 ng/ml； RSDs of inter-day and intra-day were all lower than 10％； method recovery was higher than 90％ （RSD＜8％）， and extraction recovery was higher than 70％ （RSD＜8％）. The plasma concentrations of voriconazole in 10 patients with invasive fungal infection determined by this method were 507.33-7 011.24 ng/ml， and those of 3 patients were outside the recommended treatment concentration range. CONCLUSIONS： The established method is fast， accurate and sensitive， and can be applied for the therapeutic drug monitoring of voriconazole. |
| 期刊： | 2016年第27卷第29期 |
| 作者： | 钟皎，郝琨，裴泽军 |
| AUTHORS： | ZHONG Jiao，HAO Kun，PEI Zejun |
| 关键字： | 伏立康唑；超高效液相色谱-串联质谱法；血药浓度；治疗药物监测；侵袭性真菌感染 |
| KEYWORDS： | Voriconazole； UPLC-MS/MS； Plasma concentration； Therapeutic drug monitoring； Invasive fungal infection |
| 阅读数： | 388 次 |
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