Posaconazole Trough Level Measurement Tests
High-performance liquid chromatography (HPLC) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) are the recommended tests for measuring posaconazole trough levels. 1, 2, 3
Testing Methods for Posaconazole Trough Levels
Primary Testing Methods
- HPLC with fluorescence detection: A validated method that can accurately measure posaconazole concentrations in serum/plasma 2
- LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry): Considered the gold standard for posaconazole measurement due to its high sensitivity and specificity 4, 3, 5
- UPLC-MS/MS (Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry): A newer, faster method with excellent precision 6
Alternative Method
- Bioassay: A sensitive microbiological method using Candida albicans mutants that can be used as an alternative when chromatographic methods are unavailable 6
Timing and Target Levels for Monitoring
According to the European Society of Clinical Microbiology and Infectious Diseases guidelines:
- Posaconazole plasma trough levels should be monitored on day 5 of therapy or soon thereafter 1
- For prophylaxis: Target level >0.7 mg/L 7
- For treatment of invasive aspergillosis: Target level >1.0 mg/L 7
- Upper safety threshold: 3.75 mg/L (provisional cutoff used in pharmacokinetic studies) 1
Clinical Considerations for Testing
- Repeated monitoring is indicated until steady-state level in the therapeutic range is confirmed 7
- Additional monitoring is recommended when:
Technical Aspects of Testing Methods
- HPLC methods typically use fluorescence detection (excitation 260 nm, emission 350 nm) 2
- LC-MS/MS methods often use protein precipitation for sample preparation and can detect multiple azole antifungals simultaneously 3, 5
- Most methods require only a small volume of plasma/serum (100 μL) 2, 4, 5
- Detection limits for posaconazole range from approximately 3-10 μg/L depending on the method 3, 5
Common Pitfalls and Caveats
- Variable oral bioavailability of posaconazole can lead to unpredictable serum concentrations, especially with the suspension formulation 2, 6
- Studies have shown that many patients (up to 39%) fail to achieve target trough levels with standard dosing 6
- Patients receiving posaconazole suspension may require more frequent monitoring due to variable absorption 7
- If therapeutic levels cannot be achieved with oral suspension, consider switching to tablet or intravenous formulation 7