Internal standard variability: root cause investigation, parallelism for evaluating trackability and practical considerations

Zhang J, Dasgupta A, Ayala R, Bonapace C, Kassim S & Faustino PJ | Bioanalysis, 16(15), 771–776, (2024) Keywords: • bioanalysis • challenge • internal standard variability • mass spectrometry • matrix effect • parallelism • validation Use of Internal Standards (IS) has been recommended in LC-MS/MS and LC-MS applications for quantitating drug concentrations in regulated bioanalysis in accordance with the 2022 FDA “M10 Bioanalytical Method Validation and Study Sample Analysis” Guidance (2022 FDA M10 BMV Guidance) [1]. Due to the complexity of biological samples, sample processing and instruments, a certain level of IS response variability (ISV) within a run or...