Metrological approaches to organic chemical purity: primary reference materials for vitamin D metabolites

Published

September 7, 2015

Author(s)

Michael A. Nelson, Mary Bedner, Brian E. Lang, Blaza Toman, Katrice A. Lippa

Abstract

Given the critical role of pure, organic compound primary reference standards used to characterize and certify chemical Certified Reference Materials (CRMs), it is essential that associated mass purity assessments be fit-for-purpose, represented by an appropriate uncertainty interval, and metrologically sound. The mass fraction purities (% g/g) of 25-hydroxyvitamin D (25(OH)D) reference standards used to produce and certify values for clinical Vitamin D metabolite CRMs were investigated by multiple orthogonal quantitative measurement techniques. Quantitative 1H-nuclear magnetic resonance spectroscopy (qNMR) was performed to establish traceability of these materials to the International System of Units (SI) and to directly assess the principal analyte species. The 25(OH)D standards contained volatile and water impurities, as well as structurally-related impurities that are difficult to observe by chromatographic methods or to distinguish from the principal 25(OH)D species by one-dimensional NMR. These impurities have the potential to introduce significant biases to purity investigations in which a limited number of measurands are quantified. Combining complementary information from multiple analytical methods, using both direct and indirect measurement techniques, enabled mitigation of these biases. Purities of 25(OH)D reference standards and associated uncertainties were determined using frequentist and Bayesian statistical models to combine data acquired via qNMR, liquid chromatography with UV absorbance and atmospheric pressure-chemical ionization mass spectrometric detection (LC-UV, LC-ACPI-MS), thermogravimetric analysis (TGA), and Karl Fischer (KF) titration.

Citation

Analytical and Bioanalytical Chemistry

Volume

407

Issue

28

Pub Type

Journals

Download Paper

https://doi.org/10.1007/s00216-015-9013-7

Keywords

purity, qNMR, data combination, Vitamin D, primary standard, metrology

Citation

Nelson, M. , Bedner, M. , Lang, B. , Toman, B. and Lippa, K. (2015), Metrological approaches to organic chemical purity: primary reference materials for vitamin D metabolites, Analytical and Bioanalytical Chemistry, [online], https://doi.org/10.1007/s00216-015-9013-7 (Accessed April 24, 2024)