@entity70527 (3,3-Difluoropyrrolidin-1-yl)-((2S,4S)-4-(4-(pyrimidin-2-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone) is an inhibitor of @entity5735 ( @entity5735 ) for the treatment of @entity532 . A sensitive and selective LC-MS/MS assay capable of quantifying @entity70527 in monkey serum was required to support regulated safety studies. Due to the polar nature of this compound and for ease of sample processing, hydrophilic interaction chromatography (HILIC) was identified as an ideal assay technique. During the initial phase of method development significant peak tailing was observed. The effects of polar organic modifier percentage, buffer concentration, column particle size, and flow rate were assessed to determine the final optimal conditions. @entity70527 demonstrated a strong dependence on buffer concentration with respect to height equivalent to a theoretical plate (HETP), capacity factor (k'), and tailing factor (T). Improvements in chromatography were observed with increasing buffer concentration due to reduction of electrostatic secondary interactions with ionized @entity55042 . A plot of logk' versus percentage organic modifier at an elevated buffer concentration, produced a linear fit with a correlation coefficient of 0.996, indicating that the primary chromatographic retention mechanism was partitioning. A LC-MS/MS assay was successfully developed and validated for GLP bioanalysis of @entity70527 in monkey serum utilizing the optimized HILIC conditions. Additionally, carryover was effectively minimized through fortification of @entity10977 to the sample extract.

Remediation of undesirable secondary interactions encountered in hydrophilic interaction chromatography during development of a quantitative LC-MS/MS assay for a @entity5735 ( XXXX ) inhibitor in monkey serum.

@entity5735 :: ('1803', 'Gene') :: ['DPP-IV', 'dipeptidyl peptidase IV'] @entity10977 :: ('MESH:D019855', 'Chemical') :: ['ethylene glycol'] @entity70527 :: ('MESH:C558848', 'Chemical') :: ['PF-00734200'] @entity532 :: ('MESH:D003925', 'Disease') :: ['diabetic complications and other disorders'] @entity55042 :: ('CHEBI:37171', 'Chemical') :: ['silanols']
@entity5735 :: (1803,Gene) :: ['DPP-IV']
