超高效液相色谱法测定人血浆中伏立康唑浓度

UPLC Determination of Voriconazole in Human Plasma

目的建立一种快速、灵敏的超高效液相色谱法测定人血浆中伏立康唑浓度法,并测定肺部真菌感染患者伏立康唑的血药浓度。方法采用超高效液相色谱-二极管阵列检测法(UPLC-PDA)测定伏立康唑血药浓度,以卡马西平为内标,乙腈沉淀处理血浆样品。采用S h im-pack XR-ODSⅢ柱(1.6μm,75 L×2.0),流动相为50 mmol·L^(-1)磷酸二氢钠-乙腈(40∶60),检测波长为254 nm,流速0.4 mL·min^(-1),柱温:40℃。结果血浆中伏立康唑线性范围为0.1~10.0μg·mL^(-1)(r=0.9990),萃取回收率为74.08%~81.15%,方法回收率为96.48%~101.20%,日内、日间RSD<4.57%。结论本法快速、简便、准确,适用于临床伏立康唑血药浓度的监测和药动学研究。伏立康唑个体差异大,治疗窗窄,有必要进行治疗药物监测,及时调整用药方案,以确保用药安全、有效。

OBJECTIVE To establish a rapid and sensitive UPLC method for the determination of voriconazole in the human plasma and to apply this method to patients with pulmonary fungal infection.METHODS The UPLC-PDA was applied for determination of voriconazole concentration with carbamazpine as internal standard and plasma samples were deposited down the protein with acetonitrile.The extracts were injected onto an Shim-pack XR-ODSⅢcolumn(1.6μm,75 L×2.0)with a mobile phase composed of 50 mmol·mL^(-1) phosphate buffer solution-acetonitrile(40∶60).The detective wavelength was 254 nm.The flow rate was 0.4 mL·min-1and the column temperature was set at 40℃.RESULTS The calibration was linear in the concentration range of 0.1~10.0μg·mL^(-1)(r=0.9990).The extraction and recovery rate was 74.08~81.15%and 96.48~101.20%,respectively.The intra-and inter-day precisions were both below 4.57%.CONCLUSION UPLC was proved to be convenient,accurate and suitable which can be used for therapeutic drug monitoring and for pharmacokinetic studies of voriconazloe.The detection results of twenty patients suggest the necessity of TDM of voriconazloe in clinical practice due to the apparent individual variation of plasma concentration so that the safety and effectiveness of medication can be ensured.