Bioequivalence and Bioavailability Forum

Hello shreyas goswami,

❝ No matrix effect observed during method development and method validation but what if matrix effect observed during subject sample analysis. ISTD {labelled IS} response difference in subject sample and CC/QC sample is found more than 40 percent. Moreover CC/QC samples were interspersed with subject samples and entire batch was processed in single processing batch.

A trillion billion years ago, when companies used to buy citrate plasma from blood banks to use for QCs and calibrators, while they were using Heparin or K2EDTA tubes etc for the PK samples, this effect was seen. It could go in both directions (enhancement, suppression). I believe companies learned that regulators were not, to say the least, supporting that practice with much enthusiasm

❝ Do we need to conduct further analysis with proper investigation and what if matrix effect observed due to change in population matrix.

There are no clear rules stated anywhere what to do, but it sounds like your QC + calibrator matrix has some properties that differ from that of your samples, and some degree of investigation would be a good idea.
Can you show the data or an IS plot?

❝ Does this data accepted by regulatory agencies.

If they notice it then they are in their good right to raise a lot of questions. And they might do so.