Bioequivalence and Bioavailability Forum

Dear All,

How should the specificity experiment be designed and performed during bioanalytical method validation for Fixed Dose Combination (FDC) products using LC-MS/MS?
As per the ICH M10 section 3.2.2, Specificity,
“In the case of LC-MS based methods, to assess the impact of such substances, the evaluation may include comparing the molecular weight of a potential interfering related substance with the analyte and chromatographic separation of the related substance from the analyte.”
In FDC studies involving multiple analytes,

What is the recommended approach to ensure that the presence of one analyte at high concentration (e.g., Cmax or ULOQ) does not interfere with the accurate detection and quantification of another analyte at low concentration (e.g., LLOQ)?

Should specificity testing requires only spiking blank biological matrix samples with additional analytes at high concentrations to assess potential cross-talk or interference or is it appropriate to evaluate specificity using LLOQ-level samples for one analyte in the presence of co-administered analytes at their respective Cmax concentrations?

Regards
NK

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Edit: Guideline linked. [Helmut]