Rubidium release: a rapid and sensitive assay for amphotericin B

Area of Science:

• Mycology
• Clinical Chemistry
• Pharmacology

Background:

• Accurate measurement of antifungal drug levels is crucial for effective treatment and patient safety.
• Amphotericin B is a vital antifungal medication, but its therapeutic range requires careful monitoring.
• Existing methods for amphotericin B quantification can be complex or lack sensitivity.

Purpose of the Study:

• To develop and validate a new, sensitive assay for quantifying amphotericin B levels.
• To assess the assay's performance in biological matrices like serum and spinal fluid.
• To explore the potential for improved therapeutic drug monitoring of amphotericin B.

Main Methods:

• A novel assay was developed utilizing the release of a radioactive potassium analogue, 86rubidium (86Rb), from Candida parapsilosis.
• The assay measures the interaction of amphotericin B with the fungal cell membrane, leading to 86Rb efflux.
• Quantification was performed on serum and spinal fluid samples to determine assay sensitivity and reproducibility.

Main Results:

• The developed 86Rb-release assay demonstrated high sensitivity and reproducibility.
• Amphotericin B concentrations ranging from 0.06-2.0 mug/ml were measurable in serum.
• The assay detected as little as 0.015 mug/ml of amphotericin B in spinal fluid, indicating greater sensitivity in this matrix.

Conclusions:

• The 86Rb-release assay provides a rapid, sensitive, and reproducible method for amphotericin B quantification.
• The assay's enhanced sensitivity in spinal fluid compared to serum may be attributed to reduced binding of amphotericin B by spinal fluid components.
• This assay holds promise for improved therapeutic drug monitoring of amphotericin B, potentially optimizing patient outcomes.