A-194 Development of candidate Standard Reference Material® 1950a Metabolites in Frozen Human Plasma

Abstract

Background Standard Reference Material® (SRM) 1950 Metabolites in Frozen Human Plasma was first made available in 2011 with the intended purpose of validating methods for determining a variety of metabolites, including fatty acids, vitamins, hormones, and amino acids, as well as comparison of measurement technologies used in metabolomic studies. Given the continued demand for SRM 1950, a user survey was conducted in 2023 to inform the design of the SRM 1950a renewal material. The specifications of the renewal material and measurands for priority value assignment were based on user survey feedback. Value assignments by NIST will be based on measurements from a variety of Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed Reference Measurement Procedures (RMPs) and other higher-order methods. Methods The SRM 1950 user survey was developed in collaboration between laboratory and survey experts at NIST and administered via an online tool. Initial acceptance screening of candidate SRM 1950a was performed using an Abaxis Piccolo Xpress chemistry analyzer with Basic Metabolic Panel Plus rotors. Value assignment measurements for cholesterol, creatinine, total glycerides, urea, uric acid, homocysteine, and glucose use a combination of RMPs based on either isotope-dilution liquid chromatography-mass spectrometry (ID-LC-MS) or isotope-dilution gas chromatography-mass spectrometry (ID-GC-MS). Value assignment measurements for amino acids and fatty acids use higher-order ID-LC-tandem mass spectrometry (MS/MS) and ID-GC-MS methods, respectively. Measurement campaigns are designed to capture batch homogeneity, within-vial variation, between-vial variation, and method variation. Results Based on feedback from the SRM 1950 user survey, candidate SRM 1950a was designed with specifications similar to the original material. SRM 1950a is a pool of normal human plasma from 100 donors (50 % male, 50 % female) with a racial and ethnic distribution that approximates the current United States population. The plasma was prepared with lithium heparin anticoagulant and stored in 1 mL aliquots. Based on the chemistry analyzer results from 10 vials selected in a random stratified manner across the SRM 1950a batch, the material displayed homogeneity for urea, and glucose in addition to several other analytes not intended for value assignment. The values were within normal ranges and similar to the SRM 1950 control. Preliminary value assignment campaign data also support the overall homogeneity of SRM 1950a and target analyte values similar to the original SRM 1950. Conclusion Candidate SRM 1950a will provide a renewal batch of pooled human plasma with values assigned for priority metabolites to support validation and comparison of methods. Based on user feedback, the renewal material is designed similarly to the original SRM 1950 and will allow NIST to continue to support a variety of metabolomics measurements through a reference material once SRM 1950 is depleted.