Investigation and resolution of incurred sample reanalysis failures: two case studies.

The reanalysis of incurred bioanalytical samples (incurred sample reanalysis) provides additional data that help us to ensure that a 'validated bioanalytical method' is reproducible. While the guidelines for the conduct of incurred sample reanalysis evaluations have been well described, published information pertaining to the occurrence of failures and the manner in which they are resolved has not received the same amount of attention. The purpose of this manuscript is to describe two case studies where incurred sample reanalysis failures were encountered for small molecules, the approaches that were taken to elucidate the root cause of the failures, and the remedial actions that were implemented to prevent such failures from recurring.

Pharmacokinetics of high-dose buprenorphine following single administration of sublingual tablet formulations in opioid naïve healthy male volunteers under a naltrexone block.

Sublingual buprenorphine formulations have been developed as treatments for opioid dependence. In three studies, opioid naïve healthy male subjects received Subutex tablets (buprenorphine 2 and 8 mg [N=27] or 12 and 16 mg [N=27]) or Suboxone (two formulations) tablets (buprenorphine 8 mg/naloxone 2 mg [N=36]) sublingually, under a naltrexone block for assessment of buprenorphine pharmacokinetics and tablet disintegration times. Plasma buprenorphine was quantified up to 72 h post-dose using a sensitive LC-MS/MS assay.