The solid sample itself acts as the perfectly matrix-matched calibration standard. This approach allows for a comprehensive measurement uncertainty.

Mass spectrometry (MS) allows for monitoring growth hormone (GH) isoform compositions at high specificity. It is demonstrated that this capability can be used to reliably detect alterations as elicited by (putative) doping with 22 kDa-GH. Sample treatment consists of enzymatic protein cleavage, followed by 2-step liquid chromatography clean-up, prior to analysis by MS. The protocol does not depend on antibodies for analyte extraction at any stage. Therefore, MS opens an opportunity for independent confirmation, if combined with the antibody-based isoform differential test presently used in practice. To check the fitness-for-purpose of this concept, GH-free serum was spiked with pure 22 kDa- and 20 kDa-GH covering a representative range of concentrations (0.5-9.4 μg/L), while the 22kDa fraction was within a range of  80%-85%, or at 100%, the latter simulating an administration of 22 kDa-GH. Mean deviation of 22 kDa-fractions found was within less than 3% for samples with total GH>= 1 μg/L . Beyond this, results by antibody-free isoform-differential MS, as described, were in line with those of the World Anti-Doping Agency-approved antibody-based test for 18 native sera and 3 positive controls. In this context, relating 22 kDa-GH to total-GH rather than 22 kDa+20 kDa was considered as an alternative strategy to earlier approaches. However, 20 kDa-GH as an additional measurand, next to 22 kDa- and total-GH, provides useful extra information, as it directly indicates the presence or absence of a non-22 kDa-GH form.

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Within the Working Group on Inorganic Analysis (IAWG) of the Consultative Committee for Amount of Substance: Metrology in Chemistry and Biology (CCQM) international key comparisons and pilot studies related to inorganic analysis are carried to ensure consistency in this field at the highest level. Some of these comparisons deal directly with the preparation and characterization of monoelemental solutions or with topics, closely related. The importance of monoelemental solutions lies in the fact that almost every measurement in inorganic analysis relies on the comparison with either a reference material, or references in form of solutions, usually (mono)elemental solutions. All quantitative measurement approaches, e.g. isotope dilution or standard addition, need an accurate reference solution made from a well characterized reference material, prepared under full gravimetric control. These primary (monoelemental) solutions do not only serve as arbitrary references/calibration solutions, but they also link up measurement results to the International System of units (SI), this way establishing the so-called metrological traceability to a measurement unit of the SI. Without such solutions on the highest possible level of accuracy and with the smallest possible associated uncertainties (for e.g. element content and/or impurities), an analysis itself can never be as good as it could be with appropriate reference solutions. This article highlights select key comparisons and pilot studies dealing with monoelemental solution-related topics within the IAWG from the foundation of CCQM—25 years ago—up to latest achievements in the field of inorganic analysis.