Streamlined method development for PK analysis utilizing robotic sample preparation and ultra-fast SPE-MS/MS using a newly developed QQQ MS (Agilent)
A number of highly-automated sample preparation techniques and rapid mass spectrometry based analyses have been developed in recent years to manage the method development in recent years to manage the method development and sample throughput required for absorption, distribution, metabolism and excretion/pharmacokinetics (ADME/PK) studies in early drug discovery. In addition to fast analytical cycle times, the resulting assays must exhibit a high degree of sensitivity, specificity, and robustness. One of the most effective tools for addressing these analytical challenges is ultra-fast solid-phase extraction (SPE) coupled with tandem mass spectrometry (MS/MS). This technology reduces cycle times by 10-fold when compared with typical ultra high performance liquid chromatography (UHPLC)-MS/MS analyses. Ultra-fast SPE-MS/MS accelerates method development by enabling rapid and automated assessment of different SPE cartridges and optimization of sample wash and elution buffers.
This study describes strategies for streamlining method development using Agilent RapidFire 365 high-throughput technology with an Agilent 6470 triple quadrupole MS system. This newly developed mass spectrometer incorporates enhanced pre-filter ion optics, a curved collision cell with tapered resistive rods, and an advanced ion detector that operates at dynode acceleration potentials of up to 20 kV.