Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part II–Operations

Abstract

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly utilized in clinical laboratories because it has advantages in terms of specificity and sensitivity over other analytical technologies. These advantages come with additional responsibilities and challenges given that many assays and platforms are not provided to laboratories as a single kit or device. The skills, staff, and assays used in LC-MS/MS are internally developed by the laboratory, with relatively few exceptions. Hence, a laboratory that deploys LC-MS/MS assays must be conscientious of the practices and procedures adopted to overcome the challenges associated with the technology. This review discusses the post-development landscape of LC-MS/MS assays, including validation, quality assurance, operations, and troubleshooting. The content knowledge of LC-MS/MS users is quite broad and deep and spans multiple scientific fields, including biology, clinical chemistry, chromatography, engineering, and MS. However, there are no formal academic programs or specific literature to train laboratory staff on the fundamentals of LC-MS/MS beyond the reports on method development. Therefore, depending on their experience level, some readers may be familiar with aspects of the laboratory practices described herein, while others may be not. This review endeavors to assemble aspects of LC-MS/MS operations in the clinical laboratory to provide a framework for the thoughtful development and execution of LC-MS/MS applications.

Liquid chromatography–tandem mass spectrometry for clinical diagnostics

“…Comparative elements, such as the internal standard response of a sample measured against the mean internal standard response of quality controls in the same batch, can be evaluated for systematic errors (such as under-pipetting of the internal standard) or random error (sample-specific ion suppression). Limits for each metric can be defined in laboratory standard operating procedures and used to assess data quality prior to result release, which is an important feature of LC-MS/MS 41 .…”

“…Proficiency testing and external quality assessment are essential components of the quality management plan for clinical LC-MS/MS assays 81 . Sources of proficiency testing failures that are unique to LC-MS/MS assays include variable matrix effects, lot-to-lot reagent variation, poor specificity and non-commutability of the testing material 82 .…”

Clinical Usefulness of Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry Method for Low Serum Testosterone Measurement

“…Analytical performance characteristics, including precision, accuracy, linearity, lower limit of quantitation (LLOQ), carryover, matrix effects, and stability, were evaluated, and method comparisons were conducted in accordance with the US Food and Drug Administration Center for Drug Evaluation and Research (CDER) Bioanalytical Method Validation Guidance for Industry [ 9 ], CLSI guidelines [ 10 , 11 ], a previous study [ 12 ], and review articles on LC-MS/MS laboratory development and operation [ 13 , 14 ].…”

Calibration Practices in Clinical Mass Spectrometry: Review and Recommendations

“…The regression method, model, and fitting technique used for the measurement procedure should be tailored to the empirical data-generating process characterized during method validation. Interested readers are encouraged to read two excellent reviews by Rappold [ 42 , 43 ] to gain additional insights into method development and operationalization of clinical mass spectrometry.…”