title: Incurred sample reanalysis (ISR): a decisive tool in bioanalytical research.
abstract: The AAPS Workshop 2008 on Current Topics in GLP Bioanalysis: Assay Reproducibility for Incurred Samples was the defining moment in establishing incurred sample reanalysis (ISR) as a mandatory exercise in demonstrating assay reproducibility using incurred (study) samples. The importance of ISR can be envisaged from its role in clinical as well as non-clinical studies. Incurred samples can differ significantly in their composition when compared with the calibration standards and quality control samples that are used to validate the developed method. The present article attempts to summarize five troubleshooting cases encountered in the analyses of incurred samples for bioanalytical methods developed in our laboratory for mesalamine, hydrochlorothiazide, clopidogrel, sildenafil and rabeprazole. The issues identified were related to: sample inhomogeneity, sample processing error, impact of buffer pH during sample preparation, instability of metabolite and change in laboratory environment. The steps taken to trace and correct these incidents are discussed with adequate data. These examples will further broaden the scope and emphasize the significance of ISR. We believe this investigation will help to develop more reliable and efficient bioanalytical methods.
authors.affiliation: Bioequivalence and Bioanalytical Department, Cadila Pharmaceuticals Ltd., Ahmedabad, India. manish.yadav@cadilapharma.co.in
authors.forename: Manish
authors.initials: M
authors.lastname: Yadav
authors.forename: Pranav S
authors.initials: PS
authors.lastname: Shrivastav
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000032:analysis* / Q000493:pharmacokinetics; D016477:Artifacts; D001681:Biological Assay; D000077144:Clopidogrel; D004355:Drug Stability; D017408:Guidelines as Topic; D006801:Humans; D006852:Hydrochlorothiazide / Q000032:analysis* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D019804:Mesalamine / Q000032:analysis* / Q000493:pharmacokinetics; D010879:Piperazines / Q000032:analysis* / Q000493:pharmacokinetics; D011340:Problem Solving; D011687:Purines / Q000032:analysis / Q000493:pharmacokinetics; D011786:Quality Control; D064750:Rabeprazole; D012015:Reference Standards; D015203:Reproducibility of Results; D000068677:Sildenafil Citrate; D013048:Specimen Handling / Q000379:methods; D013450:Sulfones / Q000032:analysis* / Q000493:pharmacokinetics; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D054928:Validation Studies as Topic
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D006852:Hydrochlorothiazide; D064750:Rabeprazole; D019804:Mesalamine; D000077144:Clopidogrel; D000068677:Sildenafil Citrate; D013988:Ticlopidine