Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

How to Subscribe
MLS & MLT Comprehensive CE Package
Includes 176 CE courses, most popular
$109Add to cart
Pick Your Courses
Up to 8 CE hours
$55Add to cart
Individual course$25Add to cart
The page below is a sample from the LabCE course Vitamin D. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

Learn more about Vitamin D (online CE course)
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) combines liquid chromatography's physical separation capabilities with mass spectrophotometry's mass analysis capabilities. It has evolved into a widely used technology to perform routine tests in clinical laboratories. Historically, LC-MS/MS has been used primarily by research, pharmaceutical, or commercial laboratories. Advances in technology, decreasing costs for basic systems, intelligible software, an increased number of published protocols and methods, and the release of Food and Drug Administration (FDA)-approved kits have enabled more clinical laboratories to pursue these instruments as viable clinical analyzers.
LC-MS/MS uses two mass filters arranged sequentially with a collision cell between them. The filters can be used in static or scanning mode to select a particular mass-to-charge ratio or range. In the middle collision cell, the precursor ions collide with gas molecules and are fragmented into smaller ions, referred to as product ions. The resulting product ions are then separated and detected in a second stage of mass spectrometry.
The advantages of this methodology are that it has superior selectivity for many analytes since it recognizes them by at least two physical properties (their precursor and product ion mass). Clinical laboratories have also experienced situations in which manufacturers unexpectedly withdraw immunoassays from the market, leaving labs searching for alternate methods. LC-MS/MS also allows for versatility in enabling laboratories to offer new laboratory-developed­ tests for biomarkers or newly approved medications before FDA-approved kits or immunoassays come on the market. In addition, the sensitivity of LC-MS/MS may allow lower detection limits for some analytes compared to immunoassays and other methods. Cost is another benefit; the system allows for the simultaneous identification and quantification of several analytes of interest, which lowers the cost per test.
One disadvantage of the system is that it requires high technical expertise to develop and validate tests and troubleshoot the instruments. In addition, the FDA’s recently released draft guidance document on regulating laboratory-developed tests using this methodology could affect most tests developed and performed on LC-MS/MS. Currently, laboratories develop and validate LC-MS/MS assays according to CLIA. Because these may be FDA-approved tests, they have additional analytical validation requirements, including an evaluation of imprecision, accuracy, linearity, recovery, sensitivity, specificity, carry-over, ion suppression, acceptable sample types/collection tubes/anticoagulants, storage/transport conditions, and the establishment of reference ranges. Determining the appropriate sample preparation, column choice, mobile phase, and selection of suitable internal standards are just a few of the many challenges faced during the normal method development of an assay. Another issue is standardization. Variations between LC-MS/MS assays/ users can arise since LC-MS/MS assays are not standardized, and commercial calibrators are unavailable.