This can be a difficult aspect of biomarker measurement Z-VAD-FMK in vivo to evaluate. For example, a laboratory’s participation and success in a proficiency

testing exercise may seem to be a reasonable test for a Tier 1 study; however, many proficiency testing studies have tolerance ranges that can vary by 200% (i.e., an “acceptable” analyte concentration value can be +/− 200% of the true value). In general, the study methods should have appropriate instrumentation and describe the accompanying procedures (e.g., QC, method robustness, presence of confirmation ions, use of isotope dilution). A Tier 1 study includes instrumentation that provides unambiguous identification and quantitation of the biomarker at the required sensitivity (e.g., GC–HRMS [gas chromatography/high-resolution mass

spectrometry], GC–MS/MS, LC–MS/MS). A Tier 2 study uses instrumentation that allows for identification of the biomarker with a high degree of confidence and the required sensitivity (e.g., GC–MS, GC–ECD [gas chromatography-electron capture detector]). A Tier 3 study uses instrumentation that only allows for possible quantification of the biomarker but the method has known interferants (e.g., GC–FID [gas chromatography–flame ionization detector], spectroscopy). Biomarkers are most commonly measured and reported in units of concentration; that is, mass of biomarker/volume of biological media. There are strong effects of variable urine output

(driven by diet, exercise, check details hydration, age, disease state, etc.) on urinary biomarker concentration, and of blood volume and fat content on blood biomarker concentration. Urine biomarker concentrations have been normalized across and within subjects to correct for variable urine dilution using creatinine concentration (derived from creatine phosphate breakdown in muscle), specific gravity, urine output, and other methods, though uncorrected urinary levels in spot samples without auxiliary information are commonly reported and utilized in assessments of exposure and relationship to health outcomes (Barr et al., 2005b, LaKind and Naiman, 2008, LaKind and Naiman, 2011, Lorber Dichloromethane dehalogenase et al., 2011 and Meeker et al., 2005). There is no current consensus on the best method(s) for “correcting” urinary biomarkers measurements for variable urine dilution. Minimally, both the volume-based and a corrected (creatinine and/or other method) concentrations should be provided to allow appropriate comparison across studies. It is also instructive to obtain a full volume void and elapsed time between voids. Blood-based biomarker levels have been reported in whole blood, serum, plasma and as lipid-adjusted values. The method used to determine the lipid correction or to separate the different components of the blood fluid should be provided and all concentrations, when available, should be reported (e.g., whole volume and lipid-adjusted).