Development of an LC-MS/MS Method for Quantifying Occidiofungin in Rabbit Plasma.

Area of Science:

• Mycology and Infectious Diseases
• Pharmacology and Toxicology
• Bioanalytical Chemistry

Background:

• Rising prevalence of life-threatening fungal infections due to opportunistic pathogens.
• Increasing antifungal resistance necessitates novel therapeutic agents.
• Occidiofungin (OCF) is a unique cyclic lipoglycopeptide with broad-spectrum antifungal activity, including against resistant Candida species.

Purpose of the Study:

• To develop and validate a bioanalytical method for quantifying occidiofungin in rabbit plasma.
• To support pharmacokinetic and toxicokinetic studies of occidiofungin following intravaginal administration.
• To assess the systemic absorption of occidiofungin after topical vaginal application.

Main Methods:

• Development and validation of a quantitative bioanalytical method for occidiofungin in rabbit plasma.
• Method validation included linearity (30-15,000 ng/mL), precision, accuracy, and stability assessments.
• Analysis of rabbit plasma samples after intravaginal administration of an occidiofungin-containing hydrogel.

Main Results:

• The bioanalytical method was successfully developed and validated for occidiofungin quantification in rabbit plasma.
• Pharmacokinetic and toxicokinetic studies revealed plasma concentrations of occidiofungin were predominantly below the limit of quantification (BLOQ).
• Results suggest limited systemic absorption of occidiofungin across the vaginal epithelial membrane.

Conclusions:

• A robust bioanalytical method for occidiofungin in rabbit plasma was established.
• Occidiofungin exhibits minimal systemic exposure following intravaginal administration, suggesting a favorable local safety profile.
• Further research can focus on optimizing topical delivery and efficacy for vulvovaginal candidiasis.