Systematic investigation of the failure of one analyte during method transfer and cross check of a 4-in-1 LC-MS/MS method

摘要

The root cause was identified to be a non-specific binding (NSB) of M1 to glass vial. Because the NSB of M1 in the working solution is minor (-30.2 to -21.2% after 5 consecutive transfers, table 4) and only will negatively impact the signal noise ratio at LLOQ a revalidation of the established method was not required. New cross check experiment was conducted with M1 working solution prepared in polypropylene tube and the results passed with mean difference of 2.7% (28 out of 29 incurred samples selected, the difference for the failed one is -22.7%, table 5). Detailed method description and thorough review are critical during method transition.