Quantitation of polypeptides (glucagon and salmon calcitonin) in plasma samples by 'high resolution' on a triple quadrupole mass spectrometer.

Bioanalysis of large molecules can be challenging on LC-MS/MS due to multiply charged and endogenous interferences. While high sensitivity triple quadrupole systems (QqQ) have been commercialized recently, high-resolution MS (HRMS) systems are also available. HRMS provides alternative analysis methods, but more costly and with sensitivity lower than MRM on QqQ. QqQ is generally operated at unit resolution; however, newer systems are able to practically tune to 'high resolution'. Therefore, the advantages of both higher sensitivity of MRM on QqQ and better specificity on HRMS can possibly be combined on a QqQ to meet bioanalysis needs. Glucagon and salmon calcitonin were successfully quantified in high-resolution with fast cycle time on AB Sciex TripleQuad™ 5500. LLOQ (S/N) was increased and interferences reduced. For large molecules, the bioanalysis methods developed using high resolution on the QqQ are validated and used in preclinical and clinical studies.