ABSTRACT
Validation of LC-MS/MS assays includes an assessment of matrix effects. Hemolysis effect, a special type of matrix effect, can also have an impact on analyte quantitation. In situations where the hemolysis effect is marginal, this can be resolved simply by dilution of hemolyzed samples with plasma prior to analysis. However, in some cases, the impact can be so dramatic that analytes are completely immeasurable. In such situations, modification to the bioanalytical method will be required, including, but not limited to, adjusting the chromatographic conditions to separate interferences present in hemolyzed samples; additional sample clean-up techniques such as protein precipitation in combination with SPE or a change in extraction technique such as from SPE to a liquid-liquid extraction method. Here, we report examples from four bioanalytical methods, where the presence of hemolyzed blood in plasma was found to have an impact on analyte quantitation and a description of the solutions adopted to resolve this are provided.
Subject(s)
Blood/metabolism , Chemistry Techniques, Analytical/methods , Chromatography, Liquid/methods , Pharmaceutical Preparations/blood , Solid Phase Extraction/methods , Spectrometry, Mass, Electrospray Ionization/methods , Atorvastatin , Benzodiazepines/blood , Carbazoles/blood , Carvedilol , Hemolysis , Heptanoic Acids/blood , Microfluidics , Olanzapine , Phenylephrine/blood , Propanolamines/blood , Pyrroles/bloodABSTRACT
This event was organized by the Calibration and Validation Group (a scientific nonprofit organization based in Toronto, Canada) as a 1.5-day workshop for contract research organizations and pharmaceutical companies involved in providing bioanalytical data for bioavailability, bioequivalence, pharmacokinetic and comparability studies.
Subject(s)
Drug Storage , Laboratories , Pharmaceutical Preparations/analysis , Pharmacokinetics , Biological Availability , Biotransformation , Calibration , Drug Contamination , Humans , Laboratories/standards , Pharmaceutical Preparations/metabolism , Quality Control , Reproducibility of Results , Therapeutic Equivalency , United States , United States Food and Drug Administration/standardsABSTRACT
The purpose of this study was to determine whether the pharmacokinetics of warfarin and ciprofloxacin PR (a prolonged-release formulation of ciprofloxacin) were altered after coadministration. Eighteen healthy male volunteers were given a single oral 7.5-mg dose of warfarin, a single oral 500-mg dose of ciprofloxacin PR, or both drugs administered together in a randomized, open-label, 3-way crossover study. Ciprofloxacin concentrations, warfarin (R)- and (S)-enantiomer concentrations, prothrombin time, and activated partial thromboplastin time were measured over 120 hours following study drug administration. There were no significant differences in pharmacokinetic or pharmacodynamic parameters among treatments. A slightly greater value of half-life for (R)-warfarin was observed when coadministered with ciprofloxacin PR compared with warfarin administered alone (52.6 vs 50.1 hours, P = .029). This difference is not considered clinically relevant, because the values remain similar. These results show that warfarin pharmacokinetics and pharmacodynamics are not altered with concomitant administration of ciprofloxacin PR.
Subject(s)
Anti-Infective Agents , Anticoagulants , Ciprofloxacin , Warfarin , Adolescent , Adult , Analysis of Variance , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/pharmacokinetics , Anti-Infective Agents/pharmacology , Anticoagulants/pharmacokinetics , Anticoagulants/pharmacology , Ciprofloxacin/administration & dosage , Ciprofloxacin/pharmacokinetics , Ciprofloxacin/pharmacology , Cross-Over Studies , Delayed-Action Preparations , Drug Interactions , Half-Life , Humans , Male , Middle Aged , Partial Thromboplastin Time , Prothrombin Time , Stereoisomerism , Tablets , Warfarin/pharmacokinetics , Warfarin/pharmacologyABSTRACT
The Third American Association of Pharmaceutical Scientists/Food and Drug Administration Bioanalytical Workshop, held in 2006, reviewed and evaluated current practices and proposed that carryover and contamination be assessed not only during the validation of an assay but also during the application of the method in a study. In this article, the potential risks of carryover and contamination in each stage of a bioanalytical method are discussed, to explain to the industry why this recommendation is being made.