Aim: To report the development and validation of an LC-MS/MS method for the simultaneous determination of unconjugated payload DM4 and its metabolite S-methyl-DM4 in human plasma. Methodology: A workflow of protein precipitation followed by reduction and solid phase extraction was employed to remove antibody-maytansinoid conjugates from plasma matrix, release DM4 from endogenous conjugates, and generate a clean sample extract for analysis, respectively. Sodium adduct species of both analytes were selected for multiple reaction monitoring to meet the assay sensitivity requirement in liquid chromatography with tandem mass spectrometry. Conclusion: The method was fully validated for a dynamic range of 0.100-50.0 ng/ml for both analytes along with desired stability and acceptable incurred sample reanalysis.
Keyphrases
- simultaneous determination
- tandem mass spectrometry
- liquid chromatography
- solid phase extraction
- ultra high performance liquid chromatography
- high performance liquid chromatography
- liquid chromatography tandem mass spectrometry
- mass spectrometry
- gas chromatography
- high resolution mass spectrometry
- molecularly imprinted
- glycemic control
- high resolution
- gas chromatography mass spectrometry
- oxidative stress
- metabolic syndrome
- type diabetes
- high throughput
- ms ms
- insulin resistance
- amino acid