UPLC-MS/MS method for the determination of voriconazole plasma concentration from pediatric patients with hematologic
Zhi-Peng Wen1, Hong Zhang2, Qin Li3
1Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, Guizhou, P. R. China.
Abstract:
Untreated invasive fungal infection is one of the important risk factors affecting the prognosis of pediatric patients with hematologic tumors. Voriconazole (VOR) is the first-line antifungal drug for the treatment of Aspergillus infections. In order to reduce the risk of adverse drug reactions while producing an ideal antifungal effect, therapeutic drug monitoring was performed to maintain the VOR plasma concentration in a range of 1,000-5,500 ng/ml. In the present study, a reliable, accurate, sensitive and quick ultra-high performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of the VOR level. Protein precipitation was performed using acetonitrile, and then the chromatographic separation was carried out by UPLC using a C18 column with the gradient mobile phases comprising 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 using 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 tumors were detected using this method, and the analyzed results were used for personalized therapy.
Insights
A new ultra-high performance liquid chromatograph-tandem mass spectrometry method accurately measures voriconazole (VOR) levels. This supports personalized therapy for pediatric hematologic tumor patients with invasive fungal infections.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Pediatric Oncology
Background:
- Invasive fungal infections pose a significant risk to pediatric hematologic tumor patients.
- Voriconazole (VOR) is a primary antifungal treatment for Aspergillus infections.
- Therapeutic drug monitoring of VOR is crucial to balance efficacy and minimize adverse drug reactions, targeting plasma concentrations of 1,000–5,500 ng/ml.
Purpose of the Study:
- To develop and validate a reliable, accurate, sensitive, and rapid ultra-high performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method for determining voriconazole plasma concentrations.
- To apply this validated method for monitoring VOR levels in pediatric patients with hematologic tumors.
Main Methods:
- Developed a UPLC-MS/MS method utilizing acetonitrile for protein precipitation.
- Employed a C18 column for chromatographic separation with gradient mobile phases (0.1% methanoic acid in acetonitrile and 0.1% methanoic acid in water).
- Utilized an TSQ Endura triple quadrupole mass spectrometer in selective reaction monitoring mode for detection and validated the method per National Medical Products Administration guidelines.
Main Results:
- Successfully developed and validated a UPLC-MS/MS method for precise VOR quantification.
- Demonstrated the method's reliability, accuracy, sensitivity, and speed.
- Applied the method to measure VOR plasma concentrations in pediatric patients undergoing treatment for hematologic tumors.
Conclusions:
- The developed UPLC-MS/MS method provides a robust tool for therapeutic drug monitoring of voriconazole.
- This method enables precise measurement of VOR levels, facilitating personalized therapy for pediatric patients with hematologic tumors and invasive fungal infections.
- Optimized VOR monitoring can improve treatment outcomes and reduce adverse events in this vulnerable patient population.
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