Background: Clinical development of lesinurad, a selective uric acid reabsorption inhibitor,
required analysis of lesinurad in plasma from special patient populations.
Methods: EMA and FDA bioanalytical method validation guidance have recommended studying matrix
effects on quantitation if samples from special patient populations are to be analyzed. In addition to
lesinurad (plasma protein binding 98.2%), the matrix effects from special population plasma on the
quantitation of verapamil (PPB 89.6%), allopurinol and oxypurinol (PPB negligible) were also investigated.
Results: The plasma from special population patients had no matrix effects on the three quantification
methods with stable isotope labeled internal standard, protein precipitation extraction, and LC-MS/MS
detection. The validated lesinurad plasma quantification method was successfully applied for the pharmacokinetic
evaluations to support the clinical studies in renal impaired patients.
Conclusion: Special population plasma did not affect quantitation of drugs with a wide range of
plasma protein binding levels in human plasma. With the confirmation that there is no impact on quantification
from the matrix, the bioanalytical method can be used to support the pharmacokinetic evaluations
for clinical studies in special populations.