Review Article

Ann Lab Med 2022; 42(2): 121-140

Published online March 1, 2022

Copyright © Korean Society for Laboratory Medicine.

Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part I-Development

Brian A. Rappold , B.S.

Laboratory Corporation of America Holdings, Research Triangle Park, NC, USA

Correspondence to: Brian A. Rappold, B.S.
Laboratory Corporation of America Holdings, 1904 TW Alexander Drive, Research Triangle Park, NC 27719, USA
Tel: +1-919-224-5283
Fax: +1-919-361-7242

Received: May 11, 2021; Revised: June 25, 2021; Accepted: September 28, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


The process of method development for a diagnostic assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) involves several disparate technologies and specialties. Additionally, method development details are typically not disclosed in journal publications. Method developers may need to search widely for pertinent information on their assay(s). This review summarizes the current practices and procedures in method development. Additionally, it probes aspects of method development that are generally not discussed, such as how exactly to calibrate an assay or where to place quality controls, using examples from the literature. This review intends to provide a comprehensive resource and induce critical thinking around the experiments for and execution of developing a clinically meaningful LC-MS/MS assay.

Keywords: Tandem Mass Spectrometry, Liquid Chromatography, Method Development, Sample Preparation, Calibration, Internal Standards, Matrix Effects, Quality Control