RapidFire is a novel advanced robotics system coupled with a non-chromatographic system mass spectrometer. The typical instrument time per sample on RapidFire is 10-30 seconds, which is several times faster than chromatography based approaches. RapidFire analytics have been successfully used for high throughput in vitro assays, however, its utilization for in vitro and in vivo biopharmaceutical studies using complex matrixes (plasma, complex buffer system, etc) which have proven to be challenging. Currently industry and clinical organizations are very interested in using this innovative platform for product quality and clinical studies, but several critical analytical issues (matrix effect, carryover and specificity) have yet to be rigorously evaluated. As proof-of-concept studies, we evaluated the feasibility of utilizing RapidFire for: 1) evaluate the in vitro binding of amoxicillin and metoprolol to Kayexalate in BCS media; 2) investigate the in vitro skin permeation of four sunscreen UV filters and two excipients using complex receptor media; 3) in vivo biopharmaceutical analysis of bupropion and its three pharmacologically active metabolites in human plasma. Critical method development issues such as the matrix effect, carry-over and specificity in complex matrices as well as bioanalytical validation parameters such as accuracy, precision, analytical range were systematically investigated in all three studies. The analytical methods (sample preparation, RapidFire, MS/MS methods) were developed and validated according to the requirements of the FDA Bioanalytical Method Validation Guidance. The analytical methods for the three proof-of-concept studies were determined to be accurate, precise, specific and linear over the corresponding analytical ranges. Comparable accuracy, precision, linearity, and sensitivity were achieved with analysis speeds 20 to 30-folds faster than conventional liquid chromatography based MS or tandem MS (QQQ or Q-TOF) method. Quantitation data for ~15 analytes in the three studies obtained from RapidFire were found to correlate well with data from previously validated UPLC-MS and UHPLC-MS/MS (Q-TOF) methods. In summary, advanced analytical platforms like Rapidfire are positioned to conduct pharmaceutics and biopharmaceutics studies to support regulatory studies and advance capability and readiness.

Advanced robotics coupled with a non-chromatographic mass spectrometry platform to address complex matrixes for in vitro and in vivo biopharmaceutical studies

256th National Meeting (2018)

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