UPLC-MS/MS method for the determination of voriconazole plasma concentration from pediatric patients with hematologic tumor: an application towards personalized therapy
Biomed Chromatogr. 2022 Feb 18:e5356. doi: 10.1002/bmc.5356. Online ahead of print.
Untreated invasive fungal infection (IFI) is one of the important risk factors affecting the prognosis of pediatric patients with hematologic tumor. Voriconazole (VOR) is the first line anti-fungal drug for the treatment of Aspergillus infections. In order to reduce the risk of adverse drug reaction while producing ideal anti-fungal effect, therapeutic drug monitoring (TDM) was performed to maintain VOR plasma concentration in a range of 1000 to 5500 ng/ml. In present study, a reliable, accurate, sensitive, and quick ultra-high performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method was developed for determination of VOR level. Protein precipitation was performed using acetonitrile, and then the chromatographic separation was carried out by UPLC with C18 column using the gradient mobile phase made by 0.1% methanoic acid in acetonitrile (A) and 0.1% methanoic acid in water (B). In the selective reaction monitor mode, the mass spectrometric detection was carried out by an TSQ Endura triple quadruple mass spectrometer. The performance of this UPLC-MS/MS method was validated as per the National Medical Products Administration for Bioanalytical Method Validation. Additionally, the plasma concentrations of VOR in pediatric patients with hematologic tumor were detected by this method, and the analyzed results were used for personalized therapy.