Regulated Bioanalysis of Liposomal Amphotericin B to Support Pharmacokinetic Studies of Liposomal Drugs

Abstract

Background: Because of the delicate nature of liposomes, bioanalysis of free and liposomal-encapsulated drugs is among the most challenging assays to perform. Current regulatory guidance for bioanalysis is not sufficient to address the complexity of this particular formulation. Method & results: Three individual LC–MS/MS methods to quantify free amphotericin B (10–3000 ng/ml) and encapsulated amphotericin B (100–50,000 ng/ml) in pretreated human plasma and total amphotericin B (100–50,000 ng/ml) in human plasma were fully validated and applied to a bioequivalence study. The acceptance criteria and experimental design of additional validation tests using cross quality control were carefully deliberated a priori and included in the sample analysis as well. Discussion: Additional validation tests are necessary to demonstrate that the measured concentration of the intended component is accurate and free of interference from other coexisting components in the sample. These practices can be used as guidance for future liposomal drug method validation.

Keywords::

• cross QC
• encapsulated drug
• free drug
• LC–MS/MS
• liposomal amphotericin B

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/bio-2021-0281

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/bio-2021-0281

Financial & competing interests disclosure

This research project is funded by Outstanding Scientific Fund of Shengjing Hospital (M0779, Shenyang, China) and National Natural Science Foundation of China (grant no. 82073936). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Data sharing statement

The authors certify that this manuscript reports original clinical trial data from NMPA clinical trials CTR20200885 and CTR20201717. No individual participant data that underlies the results reported in the article will be available, and nor will information regarding the study protocol or statistical analysis, beyond what is reported in the text.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.