@entity69544 and @entity69545 are new nonpeptide @entity4756 NK3 receptor antagonists with different lipophilicity and solubility. We have developed and validated two separate, simple HPLC methods for quantitation of these two compounds in plasma to support oral pharmacokinetic/bioavailability studies in @entity35 . The two compounds in plasma were extracted on cyano SPE cartridges with different washing schemes to optimize extraction efficiency and chromatographic specificity. The analytes and internal standard in the resulting extracts were chromatographed on a C18 HPLC column, using mobile phases containing different @entity1391 buffer strengths and @entity1626 concentrations. Both compounds were detected using UV, Peak area ratios were proportional over the concentration range of 50-3000 ng ml-1 for @entity69544 , and 100-1500 ng ml-1 for @entity69545 . Stability profiles of both drugs and internal standard in @entity35 plasma at 37 degrees C and in injection solvent at ambient temperature were good. Assay precision, based on quality controls, was < 5.6% and 13.4% (%RSD) for @entity69544 and @entity69545 , respectively. Similarly, assay accuracy for both compounds was within +/- 7.1% and +/- 6.0% (%RE), respectively. The HPLC methods were successfully applied to assay samples from two oral bioavailability studies. Oral bioavailability studies were conducted for each compound in @entity35 receiving a PO dose of 20 mg kg-1 or an i.v. dose of 5 mg kg-1. Despite their difference in lipophilicity and solubility, the absolute oral bioavailability of @entity69544 (5.3 +/- 4.8%) is similar to that of @entity69545 (8.8% +/-3.2%).

Development and application of sensitive HPLC assays for NK3 antagonists in XXXX plasma.

@entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity1626 :: ('MESH:C032159', 'Chemical') :: ['acetonitrile'] @entity69545 :: ('MESH:C113017', 'Chemical') :: ['CAM 5187'] @entity1391 :: ('CHEBI:26020', 'Chemical') :: ['phosphate'] @entity69544 :: ('MESH:C113016', 'Chemical') :: ['CAM 5500'] @entity4756 :: ('MESH:D015320', 'Chemical') :: ['tachykinin']
@entity35 :: (10116,Species) :: ['rat']
