An Overview on LC-MS Chromatography and its Qualification

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Pavithra B
Praveen Kumar SU
Karthik R
Jasmin Sajini R


Liquid chromatography and mass spectrometry (LC/MS) is a technique that couples the action of separation of analyte done by liquid chromatography subsequently analysis of separated analyte characteristics done by mass spectrometry. LC/MS is now being put forward by the analyst for the determination of identity, purity, quality, quantity, structural elucidation and molecular weight of unknown compounds. It is a powerful analytical technique that combines the resolution of liquid chromatography with the detection specificity of mass spectrometry. Liquid chromatography (LC) separates sample components and injects them into a mass spectrometer where MS align and detects charged ions. LC-MS also widely being used in evaluation and interpretation of bioavailability, bioequivalence and pharmacokinetic data in bioanalytical studies. LCMS is also playing an important role in the qualitative and quantitative determination of known pollutants, Food safety and development, product quality control such as the quantitation of residual veterinary drugs, food additives and the composition analysis of supplements and organic foods. This review focussed on the qualification of this analytical instrument LC-MS, where Analytical instrument qualification is collective document which provides evidence that instrument performs as per standards suitably for its intended application. Qualification of analytical instrument is usually done regularly on short term or long term to generate a validated data integrity.  As AIQ is a continuous process over lifetime of instrument which comprises of DQ, IQ, OQ, PQ; on risk assessment analysis it provides information on requalification step. When an instrument meet standard, manufacturer functional and operational specification thereby it complies with User Requirement Specification, then an analytical instrument said to a qualified one.

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Pavithra B, Praveen Kumar SU, Karthik R, & Jasmin Sajini R. (2023). An Overview on LC-MS Chromatography and its Qualification. Journal of Coastal Life Medicine, 11(1), 1421–1430. Retrieved from


James J Pitt. Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry. Clinical Biochemist Reviews. 2009 Feb; 30(1): 19–34.

Muller M, Volkel W.` The use of liquid chromatography/mass spectrometry (LC/MS) in biological monitoring. Biomonitoring Methods. 2012 Jan. 11:2007.

Taylor P. J. Matrix effects: The Achilles heel of quantitative high-performance liquid chromatography-electrospray-tandem mass spectrometry. Clinical Biochemistry. 2005. 38: 328-334.

Mei H, Hsieh Y, Nardo C, Xu X, Wang S, Korfmacher W A. Investigation of matrix effects in bioanalytical high-performance liquid chromatography/tandem mass spectrometric assays: application to drug discovery. Rapid Communication in Mass Spectrometry. 2002. 17: 97-103.

Siv kumar. Concept of URS, Design Qualification, Installation Qualification, Operational Qualification, Performance Qualification. Pharmaceutical Guidance- Audit and guidelines. 2019 July 11. Available on

Surendra k Bansal, Thomas Layloff, Emest D Bush, Marta Hamilton, Edward A Hankinson, et al. Qualification of Analytical Instruments for use in the pharmaceutical industry: A Scientific Approach. American Association of Pharmaceutical Scientists.2004;5(1):22.

Devesh Kapoor, Ruchi Vyas, Diwaker Dadrwal. An overview of analytical instrument qualification with reference of pharmaceutical industry. Journal of Drug Delivery and Therapeutics. 2018. 8(5):99-103.

Armin Groh, Bernd Renger, Claus Feussner, Hermann Wätzig, Heidemarie Höwer-Fritzen, Lukas Kaminski, et al. Why System Suitability Tests Are Not a Substitute for Analytical Instrument Qualification (Part 3): Performance Qualification (PQ). LCGC Europe. 2011; 24: 8.

Mike Sargent. Guide to achieving reliable quantitative LC-MS measurements. National Measurement System. RSC Analytical Methods Committee.2013.

U.S. Food and Drug Administration [Internet]. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the Determination of NDMA in Ranitidine Drug Substance and Solid Dosage Drug Product. 2019 Oct 17. Available from: https://www.fda. gov/media/131868.

Waters Qualification Workbook. Acquity UPLC I- class systems with UV Detectors using Mass Lynx v4.1. Recommended installation qualification procedure: IQ.

Waters Qualification Workbook. Acquity UPLC I- class systems with UV Detectors using Mass Lynx v4.1. Recommended operational and performance qualification procedure: OQ & PQ.

LC-MS setup [internet]. University of Washington's Proteomics Resource (UWPR). 2019 Sep 09. Available from: docs/protocols05/ UWPR_LC_MS _setup.

D.Gowrisankar, K.Abbulu, O.Bala Souri, K.Sujana .Validation and Calibration of Analytical Instruments. Journal of Biomedical Science and Research. 2010.Vol 2 (2): 89-99.

Waters Qualification Workbook. Waters Xevo TQ-XS Mass Spectrometer (MassLynx 4.2). Installation Qualification Procedure: IQ.

Careri, M., Mangia, A. Validation and qualification: the fitness for purpose of mass spectrometry-based analytical methods and analytical systems. Analytical and Bioanalytical Chemistry. 2006. 386, 38–45.

Rakesh Das, Subhasis Dan, and Tapan Kumar Pal. Method development and validation of liquid chromatography-tandem/mass spectrometry for aldosterone in human plasma: Application to drug interaction study of atorvastatin and Olmesartan combination. Journal of Advanced Pharmaceutical Technology and Research. 2014 Jul-Sep; 5(3): 108–114.

Waters Qualification Workbook. Waters Xevo TQ-XS Mass Spectrometer (MassLynx 4.2). Operational Qualification and Performance Qualification Procedure: IQ.

Emergency Response and Air Toxicants Branch, Division of Laboratory Sciences, National Center for Environmental Health [internet]. Laboratory Procedure Manual. HPLC - APCI Tandem Mass Spectrometry. 2003 Dec 5. Available from: es/nhanes_05_06/cot_d_met_cotinine.

Jeremy Dowling, Richard Hartwick, Jonathan Crowther, Bill Ciccone. Performance Qualification of HPLC Instrumentation in Regulated Laboratories. LCGC North America. 2008 Jan 05. Volume 26, Issue 5: 464–481.

Petrovic M, Hernando MD, Díaz-Cruz MS, Barcelo D. Liquid chromatography–tandem mass spectrometry for the analysis of pharmaceutical residues in environmental samples: a review. Journal of Chromatography A. 2005 Mar 4;1067(1-2):1-4.

Gosetti F, Mazzucco E, Zampieri D, Gennaro MC. Signal suppression/enhancement in high-performance liquid chromatography tandem mass spectrometry. Journal of Chromatography A. 2010 Jun 18;1217(25):3929-37.

Rosen J, Hellenas KE. Analysis of acrylamide in cooked foods by liquid chromatography tandem mass spectrometry. Analyst. 2002;127(7):880-2.

Choi BK, Hercules DM, Gusev AI. Effect of liquid chromatography separation of complex matrices on liquid chromatography–tandem mass spectrometry signal suppression. Journal of Chromatography A. 2001 Jan 12;907(1-2):337-42.

Stahl DC, Swiderek KM, Davis MT, Lee TD. Data-controlled automation of liquid chromatography/tandem mass spectrometry analysis of peptide mixtures. Journal of the American Society for Mass Spectrometry. 1996 Jun 1;7(6):532-40.

van den Ouweland JM, Kema IP. The role of liquid chromatography–tandem mass spectrometry in the clinical laboratory. Journal of chromatography B. 2012 Feb 1; 883:18-32.

Ardrey RE. Liquid chromatography-mass spectrometry: an introduction. John Wiley & Sons; 2003 Apr 2.

Niessen WM, Tinke AP. Liquid chromatography-mass spectrometry general principles and instrumentation. Journal of Chromatography A. 1995 Jun 26;703(1-2):37-57.

Holcapek M, Jirasko R, Lisa M. Recent developments in liquid chromatography–mass spectrometry and related techniques. Journal of Chromatography A. 2012 Oct 12; 1259:3-15.

Malik AK, Blasco C, Pico Y. Liquid chromatography–mass spectrometry in food safety. Journal of Chromatography A. 2010 Jun 18;1217(25):4018-40.

Di Stefano V, Avellone G, Bongiorno D, Cunsolo V, Muccilli V, Sforza S, Dossena A, Drahos L, Vékey K. Applications of liquid chromatography–mass spectrometry for food analysis. Journal of Chromatography A. 2012 Oct 12; 1259:74-85.

Hoja H, Marquet P, Verneuil B, Lotfi H, Pénicaut B, Lachâtre G. Applications of liquid chromatography-mass spectrometry in analytical toxicology: a review. Journal of analytical toxicology. 1997 Mar 1;21(2):116-26.

Arpino b. Combined liquid chromatography/mass spectrometry. Mass Spectrometry in the Biological Sciences: A Tutorial. 1991 Dec 31; 353:253.

Covey TR, Lee ED, Bruins AP, Henion JD. Liquid chromatography/mass spectrometry. Analytical chemistry. 1986 Dec 1;58(14):1451A-61A.

Niessen WM. State-of-the-art in liquid chromatography–mass spectrometry. Journal of Chromatography A. 1999 Sep 24;856(1-2):179-97.

Vestal ML. High-performance liquid chromatography-mass spectrometry. Science. 1984 Oct 19;226(4672):275-81.

Niessen WM. Advances in instrumentation in liquid chromatography–mass spectrometry and related liquid-introduction techniques. Journal of Chromatography A. 1998 Jan 23;794(1-2):407-35.

Games DE, Hirter P, Kuhnz W, Lewis E, Weerasinghe NC, Westwood SA. Studies of combined liquid chromatography-mass spectrometry with a moving-belt interface. Journal of Chromatography A. 1981 Jan 9; 203:131-8.

Pitt JJ. Principles and applications of liquid chromatography-mass spectrometry in clinical biochemistry. The Clinical Biochemist Reviews. 2009 Feb;30(1):19.

Ardrey RE. Liquid chromatography-mass spectrometry: an introduction. John Wiley & Sons; 2003 Apr 2.

Niessen WM. Progress in liquid chromatography–mass spectrometry instrumentation and its impact on high-throughput screening. Journal of Chromatography A. 2003 Jun 6;1000(1-2):413-36.

Rivier L. Criteria for the identification of compounds by liquid chromatography–mass spectrometry and liquid chromatography–multiple mass spectrometry in forensic toxicology and doping analysis. Analytica chimica acta. 2003 Sep 15;492(1-2):69-82.

Hird SJ, Lau BP, Schuhmacher R, Krska R. Liquid chromatography-mass spectrometry for the determination of chemical contaminants in food. TrAC Trends in Analytical Chemistry. 2014 Jul 1; 59:59-72.