Evaluation of analytical performance of homocysteine LC-MS/MS assay and design of internal quality control strategy

Abstract

Objectives Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become a common technique in clinical laboratories in recent years. Because most methods are laboratory-developed tests (LDTs), their reproducibility and quality control (QC) have been controversial. In this study, Westgard Sigma Rules were used to evaluate the analytical performance and establish an individualised internal QC (IQC) strategy for these LDTs. Methods Taking the LC-MS/MS LDT method for homocysteine (Hcy) as an example, the ‘desirable specifications’ from the Biological Variation Database were used as quality goals. Based on the external quality assessment (EQA) samples, bias was calculated and the coefficient of variation (CV) was also calculated by IQC measurements for six consecutive months. The analytical performance was evaluated by calculated sigma metrics and an IQC strategy was designed using the Westgard Sigma Rules with run size. Results Over 116 days within 6 months, a total of 850 data points were collected for each of IQC 1 and IQC 2. The monthly coefficient of variation CV% was 2.57–4.01%, which was non-significant (p-value: 0.75). The absolute bias% for IQC1 and IQC2 was 1.23 and 1.87%, respectively. The allowable total error (TEa) was selected as 15.5%, Sigma metrics were 4.02 and 4.30, and the analytical performance was ‘Good’. The 13s/22s/R4s/41s multi rules (n=4, r=1) with a run size of 200 samples were suggested for the Hcy IQC scheme. The quality goal index (QGI) values were over 1.2, indicating that trueness needed to be improved. Conclusions The analytical performance of the Hcy LC-MS/MS LDT conformed to the Six Sigma rating level, achieving ‘good’ (four Sigma). Clinical practice indicated that calibration bias was the primary factor affecting trueness.

Ensure the accuracy and consistency of biochemical analyzer test results: Chemometrics for instrument and inter-instrument item comparison in Chinese hospital laboratory

“…Moreover, most laboratories issue test reports after only one test, so it is very important to conduct systematic evaluation experiments of equipment regularly. Systematic evaluation experiments can usually be carried out from two aspects: the verification or validation of the methodological performance of clinical testing items [ [9] , [10] , [11] , [12] , [13] ] and the experimental evaluation of the analytical performance of the instrument itself, but the latter is rarely studied. This study took the AU5400 and ADVIA2400 biochemical analyzers as the research objects and designed and verified the analytical performance evaluation experiments of the instruments according to the industry norms of our country and the world standards [ [14] , [15] , [16] ].…”

“…At present, there are many pieces of research on period verification, such as internal quality control and external quality assessment [ [5] , [6] , [7] , [8] ]. Almost all research on the systematic evaluation of instruments focuses on methodological performance verification and validation experiments of clinical items [ [9] , [10] , [11] , [12] , [13] ], and almost no one pays attention to the analytical performance evaluation of the instrument itself. Therefore, the research direction of our team focuses on the automatic biochemical analysis instrument itself stoichiometric scheme design and feasibility analysis.…”