Posaconazole LC-MS/MS

Patient variability in the pharmacokinetics of posaconazole supports quantitative monitoring of blood drug levels, particularly due to its variable absorption. Monitoring trough levels of posaconazole is suggested in patients with suboptimal nutritional intake (and therefore requiring food and liquid nutritional supplementation), or in patients with gastrointestinal disease such as mucositis, diarrhea, vomiting or GVHD. Monitoring trough levels of posaconazole is also suggested in patients treated with other drugs that either induce or inhibit CYP450 isoenzymes or that serve as substrates for these isoenzymes. Results may be clinically useful to determine if current dosing levels have achieved adequate therapeutic concentrations of posaconazole.

About Immunosuppressive Drug Level Monitoring

The successful management of invasive fungal infections (IFI) continues to pose a difficult challenge for physicians treating immunocompromised patients, and despite recent advances in therapy, the morbidity and mortality due to IFI remains unacceptably high.⁴ Triazole antifungal drugs are commonly used to either prevent or treat IFI in at-risk patients. However, extensive intra- and inter-patient variability is observed in the pharmacokinetics of triazole antifungal drugs. This variability supports quantitative monitoring, i.e., therapeutic drug monitoring of triazole blood drug levels.^4,5

By using drug level monitoring with timely results, the physician is able to individualize drug dosage to improve efficacy and reduce toxicity. Drug monitoring of triazoles is included in the Infectious Diseases Society of America guidelines for treating aspergillosis and candidiasis.^6,7 Recommendations indicate that blood samples should be obtained one to two weeks after the start of therapy, immediately before the next dose (“trough time”) and repeated following a change in dosage, formulation, initiation or discontinuation of an interacting medication, potential treatment failure or non-adherence to dosing schedule. Patients with altered hepatic and/or renal clearance will also benefit from drug level monitoring of triazoles.

Several triazole drugs are commonly used to treat IFI in immunocompromised patients. Voriconazole is used in treatment for a broad range of fungal infections, including invasive aspergillosis, candidiasis and other emerging IFI. Posaconazole is a broad spectrum triazole antifungal agent for treatment and prophylaxis of fungal and mold infections, including candidiasis, aspergillosis and zygomycosis. Itraconazole is used as therapy for a variety of invasive and non-invasive fungal infections, and is approved for the treatment of histoplasmosis, aspergillosis, esophageal candidiasis, and oropharyngeal candidiasis. Isavuconazole (CRESEMBA) is used to treat invasive aspergillosis and mucormycosis.¹

Posaconazole is extracted from biological matrix by simple protein precipitation with methanol followed by centrifugation. Chromatographic separation and quantitative analysis of the drug containing supernatant is performed using reversed-phase UPLC-MS/MS method. This test has not been cleared or approved for diagnostic use by the U.S. Food and Drug Administration.