Think of all the tubes of blood that are drawn and transported to the clinical laboratory to be processed every day. After being logged in, they make their way to an instrument for analysis, wherever that might be: in the same room, down the hall, across town, or a plane ride away. During that time, as the samples sit at room temperature, refrigerated, or on dry ice, chemical processes continue, albeit at varied rates for different molecules. Indeed, even at subfreezing temperatures enzymatic lipolysis takes place (1). Oxidation, which could obscure endogenous oxidation events that may represent important novel biomarkers, can also occur (2). Clinical chemists are careful to evaluate these and other preanalytical variables that may affect assay results for their patients. Unfortunately, there is often no way to tell if something has gone unexpectedly wrong with sample collection, storage, or preparation until it is too late and a result is already in a medical record being interpreted by a care provider. It would be highly desirable to have an easy way to tell if a sample has been compromised in a way that would effectively eliminate the possibility of accurate protein quantification, but this option will never be possible for the traditional automated immunochemical platforms that serve as the mainstay in clinical laboratories. In addition to the preanalytical issues with clinical assays, a variety of analytical problems can also complicate the analysis of a biomarker in human samples. For example, lipemia and hyperproteinemia can interfere with the indirect potentiometric measurement of sodium (3). In addition, interconversion of folate metabolites from lysed erythrocytes occurs during the deconjugation reaction before certain chromatographic assays (4). In this issue of Clinical Chemistry , Bystrom et al. (5) describe taking …