Development of an LC-MS/MS Method for Quantifying Occidiofungin in Rabbit Plasma
Andrew Cothrell1, Ravi S Orugunty2, Leif Smith1
1Department of Biology, Texas A&M University, College Station, Texas, USA.
Abstract:
Fungal infections are caused by opportunistic pathogens that can be life threatening and have been growing in prevalence. Many clinically relevant pathogens have resistance to or are developing resistance to the commonly used antifungal treatments. Occidiofungin (OCF) is a unique cyclic lipoglycopeptide with a novel structure that includes noncanonical amino acid in its covalent structure. It exhibits broad spectrum antifungal activity and has activity against drug resistant Candida species. Occidiofungin is a fungicidal compound that has a novel mechanism of action in which it disrupts higher order actin structures. Currently, occidiofungin is being developed for use in treating vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC). This study describes the development and application of a bioanalytical method for the quantification of occidiofungin in rabbit plasma. Method development was performed to quantify occidiofungin in rabbit plasma after intravaginal administration of a hydrogel containing occidiofungin. The method was validated with a linear range of 30-15 000 ng/mL in rabbit plasma. Precision, accuracy, calibration curve linearity, and stability of drug in plasma were established in quality controls. Extract stability, matrix effects, and recovery of drug in the extract were also determined. This study supported a repeat dose toxicity study in rabbits to determine occidiofungin pharmacokinetics and toxicokinetics. The pharmacokinetic and toxicokinetic primarily showed plasma concentrations of occidiofungin below the limit of quantification (BLOQ), suggesting that OCF-B does not readily cross the vaginal epithelial membrane.
Insights
Occidiofungin (OCF), a novel antifungal, shows promise for treating fungal infections. A new bioanalytical method confirmed OCF plasma levels remain below quantification limits after vaginal administration, indicating minimal systemic absorption.
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.
More Related Videos
09:58Spatial Quantification of Drugs in Pulmonary Tuberculosis Lesions by Laser Capture Microdissection Liquid Chromatography Mass Spectrometry LCM-LC/MS
Published on: April 18, 2018
10:01Quantification of Fungal Colonization, Sporogenesis, and Production of Mycotoxins Using Kernel Bioassays
Published on: April 23, 2012