Development of Certified Reference Material for Amino Acids in Dried Blood Spots and Accuracy Assessment of Disc Sampling.

To achieve the measurement reliability of amino acids used as diagnostic markers in clinical fields, establishing a reference measurement system is required, in which certified reference materials (CRMs) are an essential step in the hierarchy of measurement traceability. This study describes the development of dried blood spot (DBS) CRMs for amino acid analysis with complete measurement traceability to the International System of Units (SI). Six essential amino acids─proline, valine, isoleucine, leucine, phenylalanine, and tyrosine─were analyzed using isotope-dilution liquid chromatography-mass spectrometry (ID-MS). For minimizing measurement bias and uncertainty overestimation, whole spots with 50 µL of whole blood were adopted in the certification. The between-spot homogeneities by whole spot sampling were lower than 2.1%. The relative expanded uncertainties of the six amino acids in the developed DBS CRMs were lower than 5.7% at 95% confidence. The certified values are traceable to SI through both gravimetric preparation and the primary method in certification, ID-MS. Comparison among DBS testing laboratories revealed discrepancies between the whole spot and disc sampling methods. The actual sampling volume was accurately estimated by weighing, which revealed the possibility of underestimation in routine DBS testing. The candidate CRMs can support the standardization of DBS testing for amino acids through the qualification and validation of many kinds of measurement procedures to compensate the measurement bias caused by matrix-specific sampling error.

Standardization Status of Total Cholesterol Concentration Measurement: Analysis of Korean External Quality Assessment Data.

BACKGROUND: Total cholesterol concentration measurement is important in the diagnosis of dyslipidemia and evaluation of cardiovascular disease risk factors. Measurement reliability for obtaining an accurate total cholesterol concentration requires procedure standardization. We evaluated the standardization status for total cholesterol concentration measurement through Korean external quality assessment (EQA) data analysis. METHODS: This study involved 1,670 laboratories that participated in the EQA of total cholesterol concentration measurements in 2019 for 32 products from different manufacturers. The target concentrations of three quality control (QC) materials (samples A, B, and C) were measured using the reference method and compared with EQA data. The performance criteria for total cholesterol concentration measurement were based on the National Cholesterol Education Program guidelines, with ±3% inaccuracy. RESULTS: The target values and inaccuracies of the QC material based on the reference method measurements were 254.65±7.64, 108.30±3.25, and 256.29±7.69 mg/dL (6.59±0.20, 2.80±0.08, and 6.63±0.20 mmol/L) for samples A, B, and C, respectively. The performance criteria were not met in 42.7% laboratories for sample A, 68.4% of laboratories for sample B, and 38.0% laboratories for sample C. CONCLUSIONS: Despite significant efforts to accurately measure total cholesterol concentrations, further actions are needed for measurement standardization. Manufacturers reporting values that differ from target values should check calibrator traceability; additional efforts to accurately measure total cholesterol concentrations are required for laboratories that use products from these manufacturers.