Concentration Determination of Voriconazole in Human Plasma by UPLC-MS/MS and Its Clinical Application
10.6039/j.issn.1001-0408.2016.29.09
- VernacularTitle:UPLC-MS/MS法测定人血浆中伏立康唑的浓度及其临床应用
- Author:
Jiao ZHONG
;
Kun HAO
;
Zejun PEI
- Publication Type:Journal Article
- Keywords:
Voriconazole;
UPLC-MS/MS;
Plasma concentration;
Therapeutic drug monitoring;
Invasive fungal infection
- From:
China Pharmacy
2016;27(29):4064-4066,4067
- CountryChina
- Language:Chinese
-
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 per-formed 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,pos-itive 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.