LC-MS AS A VERSATILE TOOL FOR DRUG DISCOVERY, DEVELOPMENT, AND CLINICAL DIAGNOSTICS

Authors

  • SARAVANAN RAVINDRAN Department of Pharmaceutics, Faculty of Pharmacy, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India.
  • SHAIK MEHARAJ Department of Pharmaceutical Analysis, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India.
  • RAJAGANAPATHY KALIYAPERUMAL Department of Pharmacology, Faculty of Pharmacy, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2026v19i2.57475

Keywords:

Liquid Chromatography-Mass Spectrometry (LC-MS), Electrospray Ionization (ESI), Artificial Intelligence (AI) and Machine Learning (ML), Multidimensional Separation Technology, Biomolecular Research

Abstract

One of the crucial elements in the analysis of biomolecules is liquid chromatography-mass spectrometry (LC-MS), affording unique sensitivity and specificity to a broad spectrum of applications in the discovery of new drugs, proteomics, and metabolomics. Modern biomolecular science has been reshaped by new techniques in LC-MS technology by enabling the potential to deconstruct increasingly complex systems in biological and life sciences research. A highlight of current trends, hot instruments, and advancements, along with modern approaches for improvements in separations and processing the data for advancement in this sector, will also be addressed herein. Combining high-resolution MS (HRMS) and ultra-high-performance liquid chromatography (UHPLC) marks one of the most meaningful changes since this combination produces the best results, both in terms of better resolution and as regards increasing sample throughput. Many of these previous limitations for biological macromolecule analysis are fast being mitigated because improved ionization technologies, particularly in electrospray ionization and matrix-assisted laser desorption/ionization, expand the breadth of possible LC-MS analyses. Recent improvements in multidimensional separation technology and stationary phase diversity increase chromatographic efficiencies, especially to study more intricate biological matrices. Together with strategies to overcome these limitations, this paper also discusses challenges such as matrix effects, sample preparation challenges, and data quality. Researchers can uncover novel information on biomolecular interactions, disease mechanisms, and therapeutic targets by integrating state-of-the-art LC-MS technologies with innovative computational approaches. As LC-MS continues to evolve, it holds immense potential to shape the future of precision medicine and biomolecular research.

Downloads

Download data is not yet available.

References

1. Metz TO, Zhang Q, Page JS, Shen Y, Callister SJ, Jacobs JM, et al. The future of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discovery. Biomark Med. 2007;1(1):159-85. doi: 10.2217/17520363.1.1.159, PMID 19177179

2. Rischke S, Hahnefeld L, Burla B, Behrens F, Gurke R, Garrett TJ. Small molecule biomarker discovery: Proposed workflow for LC-MS-based clinical research projects. J Mass Spectrom Adv Clin Lab. 2023;28:47-55. doi: 10.1016/j.jmsacl.2023.02.003, PMID 36872952

3. De Merbel N, van Gnoth MJ, Wilson A, Blattmann P, Ingelse B, Jordan G, et al. Perspective on LC-MS(/MS) for biotherapeutic and biomarker proteins in research and regulated bioanalysis: Consolidation of European Bioanalysis Forum experience. Bioanalysis. 2024;2:1-7. doi: 10.1080/17576180.2024.2418251

4. Pavithra B, Praveen Kumar SU, Karthik R, Jasmin Sajini R. An overview on LC-MS chromatography and its qualification. J Coast Life Med. 2023;11(1):1421-30.

5. Faloye KO, Tripathi MK, Adesida SA, Oguntimehin SA, Oyetunde YM, Adewole AH, et al. Antimalarial potential, LC-MS secondary metabolite profiling and computational studies of Zingiber officinale. J Biomol Struct Dyn. 2023;42(5):2570-85. doi: 10.1080/07391102.2023.2205949, PMID 37116195

6. Cross TG, Hornshaw MP. Can LC and LC-MS ever replace immunoassays? J Appl Bioanal. 2016;2(4):108-16. doi: 10.17145/jab.16.015

7. Sharma D, Rahul M, Gupta A, Singh K. Quantitative bioanalysis by LC-MS/MS: A review. J Pharm Biomed Anal. 2010;7(1):1-9.

8. Smith BJ, Martins-de-Souza D. Biological applications for LC-MS-based proteomics. Adv Exp Med Biol. 2021;1336:17-29. doi: 10.1007/978-3-030-77252-9_2, PMID 34628625

9. Bengio Y, Courville A, Vincent P. Representation learning: A review and new perspectives. IEEE Trans Pattern Anal Mach Intell. 2013;35(8):1798-828. doi: 10.1109/TPAMI.2013.50, PMID 23787338

10. Liebisch G, Vizcaino JA, Koefeler H, Troetzmueller M, Griffiths WJ, Schmitz G, et al. Lipid Res. 2013;54:1523-30. doi: 10.1194/jlr.M035750

11. Zhu R, Song E, Hussein A, Kobeissy FH, Mechref Y. Glycoproteins enrichment and LC-MS/MS glycoproteomics in central nervous system applications. Methods Mol Biol. 2017;1598:213-27. doi: 10.1007/978- 1-4939-6952-4_9, PMID 28508363

12. Sarvani V, Elisha Raju P, Sreekanth N, Leela Madhuri P, Chandu Babu R. Role of LC-MS in drug discovery process. Int J Pharm Ther. 2013;4(3):148-53.

13. Kantheti S, Gorumutchu GP, Raju RR, Sivanadh M. Quantitative analysis of elacestrant in pharmaceutical dosage forms by UPLC-MS with emphasis on stability assessment. Asian J Pharm Clin Res. 2025;18(7):185-97. doi: 10.22159/ajpcr.2025v18i7.54496

14. Ramu C, Gayathri N, Priya G, Boobalan SK, Sekar T. Integrated phytochemical analysis of Strychnos nux-vomica using molecular spectroscopy and hyphenated chromatography. Asian J Pharm Clin Res. 2025;18(8):124-31. doi: 10.22159/ajpcr.2025v18i8.54684

15. Alvarez-Rivera G, Ballesteros-Vivas D, Parada-Alfonso F, Ibañez E, Cifuentes A. Recent applications of high-resolution mass spectrometry for characterization of plant natural products. TrAC Trends Anal Chem. 2019;112:87-101. doi: 10.1016/j.trac.2018.12.008

16. Crutchfield CA, Clarke W. Present and future applications of high resolution mass spectrometry in the clinic. Discoveries (Craiova). 2014;2(2):e17. doi: 10.15190/d.2014.9, PMID 32309546

17. Géhin C, Holman SW. Advances in high-resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information. Anal Sci Adv. 2021;2(3-4):142-56. doi: 10.1002/ansa.202000149, PMID 38716455

18. Geiger T, Wehner A, Schaab C, Cox J, Mann M. Comparative proteomic analysis of eleven common cell lines reveals ubiquitous but varying expression of most proteins. Mol Cell Proteomics. 2012 Mar 1;11(3):M111.014050. doi: 10.1074/mcp.M111.014050, PMID 22278370

19. Prasad B, Garg A, Takwani H, Singh S. Metabolite identification by liquid chromatography-mass spectrometry. TrAC Trends Anal Chem. 2011;30(2):360-87. doi: 10.1016/j.trac.2010.10.014

20. Köfeler HC, Ahrends R, Baker ES, Ekroos K, Han X, Hoffmann N, et al. Recommendations for good practice in MS-based lipidomics. J Lipid Res. 2021;62:100138. doi: 10.1016/j.jlr.2021.100138, PMID 34662536

21. Zhang H, Lu KH, Ebbini M, Huang P, Lu H, Li L. Mass spectrometry imaging for spatially resolved multi-omics molecular mapping. Npj Imaging. 2024;2(1):20. doi: 10.1038/s44303-024-00025-3, PMID 39036554

22. Bekker-Jensen DB, Martínez-Val A, Steigerwald S, Rüther P, Fort KL, Arrey TN, et al. A compact quadrupole-Orbitrap mass spectrometer with FAIMS interface improves proteome coverage in Short LC gradients. Mol Cell Proteomics. 2020;19(4):716-29. doi: 10.1074/mcp. TIR119.001906, PMID 32051234

23. Zhang C, Le Dévédec SE, Ali A, Hankemeier T. Single-cell metabolomics by mass spectrometry: Ready for primetime? Curr Opin Biotechnol. 2023;82:102963. doi: 10.1016/j.copbio.2023.102963, PMID 37356380

24. Hale OJ, Illes-Toth E, Mize TH, Cooper HJ. High-field asymmetric waveform ion mobility spectrometry and native mass spectrometry: Analysis of intact protein assemblies and protein complexes. Anal Chem. 2020;92(10):6811-6. doi: 10.1021/acs.analchem.0c00649, PMID 32343119

25. Thompson A, Schäfer J, Kuhn K, Kienle S, Schwarz J, Schmidt G, et al. Tandem mass tags: A novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem. 2003;75(8):1895-904. doi: 10.1021/ac0262560, PMID 12713048

26. Ferreira CR, Yannell KE, Jarmusch AK, Pirro V, Ouyang Z, Cooks RG. Ambient ionization mass spectrometry for point-of-care diagnostics and other clinical measurements. Clin Chem. 2016;62(1):99-110. doi: 10.1373/clinchem.2014.237164, PMID 26467505

27. Kong J, Yu S. Fourier transform infrared spectroscopic analysis of protein secondary structures. Acta Biochim Biophys Sin (Shanghai). 2007;39(8):549- 59. doi: 10.1111/j.1745-7270.2007.00320.x, PMID 17687489

28. Vargas Medina DA, Maciel EV, Lanças FM. Miniaturization of liquid chromatography coupled to mass spectrometry: Chip-based LC-MS devices. TrAC Trends Anal Chem. 2020;131:116003. doi: 10.1016/j. trac.2020.116003

29. Zhang H, Zhang J, Yuan C, Zhang D, Lu D, Chen S, et al. Mass spectrometry imaging combined with artificial intelligence: Recent advances and perspectives. Trends Anal Chem. 2024;178:117834. doi: 10.1016/j.trac.2024.117834

30. Zhao L, Li F. UHPLC-MS strategies and applications for pharmacokinetics and drug metabolism. TrAC Trends Anal Chem. 2014;63:170-9. doi: 10.1016/j.trac.2014.07.014

31. van den Hurk RS, Pursch M, Stoll DR, Pirok BW. Recent trends in two-dimensional liquid chromatography. TrAC Trends Anal Chem. 2023;166:117166. doi: 10.1016/j.trac.2023.117166

32. Ho CS, Lam CW, Chan MH, Cheung RC, Law LK, Lit LC, et al. Electrospray ionisation mass spectrometry: Principles and clinical applications. Clin Biochem Rev. 2003;24(1):3-12. PMID 18568044

33. Nielen MW, Hooijerink H, Zomer P, Mol JG. Desorption electrospray ionization mass spectrometry in the analysis of chemical food contaminants in food. TrAC Trends Anal Chem. 2011;30(2):165-80. doi: 10.1016/j.trac.2010.11.006

34. Bueno MJ, Agüera A, Gómez MJ, Hernando MD, García-Reyes JF, Fernández-Alba AR. Application of liquid chromatography/quadrupole-linear ion trap mass spectrometry and time-of-flight mass spectrometry to the determination of pharmaceuticals and related contaminants in wastewater. Anal Chem. 2007;79(24):9372-84. doi: 10.1021/ac0715672, PMID 18001124

35. Ens W, Standing KG. Hybrid quadrupole/time-of-flight mass spectrometers for analysis of biomolecules. Methods Enzymol. 2005;402:49-78. doi: 10.1016/S0076-6879(05)02002-1, PMID 16401506

36. Gaspari M, Cuda G. Nano LC-MS/MS: A robust setup for proteomic analysis. Methods Mol Biol. 2011;790:115-26. doi: 10.1007/978-1- 61779-319-6_9, PMID 21948410

37. Ozohanics O, Ambrus A. Hydrogen-deuterium exchange mass spectrometry: A novel structural biology approach. Life (Basel). 2020;10(11):286. doi: 10.3390/life10110286, PMID 33203161

38. Horvatovich P, Hoekman B, Govorukhina NI, Bischoff R. Multidimensional chromatography coupled to mass spectrometry in analysing complex proteomics samples. J Sep Sci. 2010;33(10):1421-37. doi: 10.1002/jssc.201000050, PMID 20486207

39. Aydoğan C, Rigano F, KujovskáKrčmová L, Chung DS, Macka M, Mondello L. Miniaturized liquid chromatography in molecular omics applications. Anal Chem. 2020;92(17):11485-97. doi: 10.1021/acs. analchem.0c01957

40. Beccaria M, Cabooter D. Current developments in LC-MS for pharmaceutical analysis. Analyst. 2020;145(4):1129-57. doi: 10.1039/ C9AN02145K, PMID 31971527

41. Korfmacher WA. Principles and applications of LC-MS in new drug discovery. Drug Discov Today. 2005 Oct 15;10(20):1357-67. doi: 10.1016/S1359-6446(05)03620-2, PMID 16253874

42. Metowogo K, Eklu-Gadegbeku K, Agbonon A, Aklikokou KA, Gbeassor M. Gastroprotective effect of hydroalcoholic extract of Aloe buettneri. Iran J Pharm Res. 2011;10(1):69-74. PMID 24363683

43. Nazario CE, Silva MR, Franco MS, Lanças FM. Evolution in miniaturized column liquid chromatography instrumentation and applications: An overview. J Chromatogr A. 2015 Nov 20;1421:18-37. doi: 10.1016/j.chroma.2015.08.051, PMID 26381569

44. Andersson ME, Aslan D, Clarke A, Roeraade J, Hagman G. Generic chiral liquid chromatographic screens using a column-switching system. J Chromatogr A. 2003;1005(1-2):83-101. doi: 10.1016/S0021- 9673(03)01001-9

45. Akimaru M, Okubo K, Hiruta Y, Kanazawa H. Temperature-responsive solid-phase extraction column for biological sample pretreatment. Anal Sci. 2015;31(9):881-6. doi: 10.2116/analsci.31.881, PMID 26353953

46. Alanazi S. Recent advances in liquid chromatography-mass spectrometry applications. Anal Sci Adv. 2025;6(1):e70024. doi: 10.1002/ansa.202400024

47. Basheer C, Alhooshani K, Abdulkadir NA, Kanimozhi S. Sample preparation of biological samples for LC-MS analysis. In: Basheer C, editor. Sample Preparation Techniques in Analytical Chemistry. Amsterdam: Elsevier; 2012. p. 1-25.

48. Baysoy A, Bai Z, Satija R, Fan R. The technological landscape and applications of single-cell multi-omics. Nat Rev Mol Cell Biol. 2023;24(10):695-713. doi: 10.1038/s41580-023-00615-w, PMID 37280296

49. Bretherton R, Bugg D, Olszewski E, Davis J. Regulators of cardiac fibroblast cell state. Matrix Biol. 2020;91-92:117-35. doi: 10.1016/j. matbio.2020.04.002, PMID 32416242

50. Buettner F, Natarajan KN, Casale FP, Proserpio V, Scialdone A, Theis FJ, et al. Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells. Nat Biotechnol. 2015;33(2):155-60. doi: 10.1038/nbt.3102, PMID 25599176

51. Challen B, Cramer R. Advances in ionisation techniques for mass spectrometry-based omics research. Proteomics. 2022;22(15- 16):e2100394. doi: 10.1002/pmic.202100394, PMID 35709387

52. Hale OJ, Cooper HJ. Native mass spectrometry for the study of protein structure and interactions. Analyst. 2021;146(10):2951-64. doi: 10.1039/D0AN02320A

53. Kelleher NL. Top-down proteomics. Anal Chem. 2004;76(11):197A- 203. doi: 10.1021/ac041560f, PMID 15190879

54. Lanucara F, Holman SW, Gray CJ, Eyers CE. The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics. Nat Chem. 2014;6(4):281-94. doi: 10.1038/nchem.1889, PMID 24651194

55. Mann M, Kelleher NL. Precision proteomics: The case for top-down approaches. Proc Natl Acad Sci U S A. 2008;105(47):18132-8. doi: 10.1073/pnas.0800788105, PMID 18818311

56. Nilsson T, Mann M, Aebersold R, Yates JR, Bairoch A, Bergeron JJ. Mass spectrometry in high-throughput proteomics: Ready for the big time. Nat Methods. 2010;7(9):681-5. doi: 10.1038/nmeth0910-681, PMID 20805795

57. Zhang Y, Fonslow BR, Shan B, Baek MC, Yates JR 3rd. Protein analysis by shotgun/bottom-up proteomics. Chem Rev. 2013;113(4):2343-94. doi: 10.1021/cr3003533, PMID 23438204

58. Aebersold R, Mann M. Mass-spectrometric exploration of proteome structure and function. Nature. 2016;537(7620):347-55. doi: 10.1038/ nature19949, PMID 27629641

59. Neely BA, Dorfer V, Martens L, Bludau I, Bouwmeester R, Degroeve S, et al. Toward an integrated machine learning model of a proteomics experiment. J Proteome Res. 2023;22(3):681-96. doi: 10.1021/acs. jproteome.2c00711, PMID 36744821

60. Lee ES, Durant TJ. Supervised machine learning in the mass spectrometry laboratory: A tutorial. J Mass Spectrom Adv Clin Lab. 2022;23:1-6. doi: 10.1016/j.jmsacl.2021.12.001, PMID 34984411

61. Feist P, Hummon AB. Proteomic challenges: Sample preparation techniques for microgram-quantity protein analysis from biological samples. Int J Mol Sci. 2015;16(2):3537-63. doi: 10.3390/ ijms16023537, PMID 25664860

62. Shishkova E, Coon JJ. Rapid preparation of human blood plasma for bottom-up proteomics analysis. Proteomics. 2021;21(19-20):e2100074. doi: 10.1002/pmic.202100074

63. Woźniak J, Nawała J, Dziedzic D, Popiel S. Overview of liquid sample preparation techniques using metal-organic frameworks as sorbents. Molecules. 2024;29(19):4752. doi: 10.3390/molecules29194752, PMID 39407677

64. Nenni M, Doğan A, Çelebier M, Soyseven M, Kaynak MS, Aboul- Enein HY, et al. Ultrafiltration-based sample preparation and HPLC-UV determination of diclofenac in human plasma samples. Turk J Chem. 2022;46(3):777-85. doi: 10.55730/1300-0527.3367, PMID 37720620

65. Wong MM, Holzheuer WB, Webster GK. A comparison of HPLC and SFC chiral method development screening approaches for compounds of pharmaceutical interest. Curr Pharm Anal. 2008 May 1;4(2):101-5. doi: 10.2174/157341208784246288

66. Daryanavard SM, Zolfaghari H, Abdel-Rehim A, Abdel-Rehim M. Recent applications of microextraction sample preparation techniques in biological samples analysis. Biomed Chromatogr. 2021;35(7):e5105. doi: 10.1002/bmc.5105, PMID 33660303

67. Niu Z, Zhang W, Yu C, Zhang J, Wen Y. Recent advances in biological sample preparation methods coupled with chromatography, spectrometry and electrochemistry. TrAC Trends Anal Chem. 2018;108:179-90. doi: 10.1016/j.trac.2018.08.017

68. Okubo K, Ikeda K, Oaku A, Hiruta Y, Nagase K, Kanazawa H. Protein purification using solid-phase extraction on temperature-responsive hydrogel-modified silica beads. J Chromatogr A. 2018 Sep 21;1568:38-48. doi: 10.1016/j.chroma.2018.07.027, PMID 30033167

69. Lee S, Vu HM, Lee JH, Lim H, Kim MS. Advances in mass spectrometry-based single cell analysis. Biology (Basel). 2023;12(3):395. doi: 10.3390/biology12030395, PMID 36979087

70. Gulati GS, D’Silva JP, Liu Y, Wang L, Newman AM. Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics. Nat Rev Mol Cell Biol. 2025 Jan;26(1):11-31. doi: 10.1038/s41580-024-00768-2, PMID 39169166

71. Tirosh I, Venteicher AS, Hebert C, Escalante LE, Patel AP, Yizhak K, et al. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature. 2016;539(7628):309-13. doi: 10.1038/nature20123, PMID 27806376

72. Chen TY, You L, Hardillo JA, Chien MP. Spatial transcriptomic technologies. Cells. 2023 Aug 10;12(16):2042. doi: 10.3390/ cells12162042, PMID 37626852

73. Liu X, Peng T, Xu M, Lin S, Hu B, Chu T, et al. Spatial multi-omics: Deciphering technological landscape of integration of multi-omics and its applications. J Hematol Oncol. 2024;17(1):72. doi: 10.1186/s13045- 024-01596-9, PMID 39182134.

74. von Gerichten J, Saunders KD, Kontiza A, Newman CF, Mayson G, Beste DJ, et al. Single-cell untargeted lipidomics using liquid chromatography and data-dependent acquisition after live cell selection. Anal Chem. 2024;96(18):6922-9. doi: 10.1021/acs.analchem.3c05677, PMID 38653330

75. Saito Y, Jinno K, Greibrokk T. Capillary columns in liquid chromatography: Between conventional columns and microchips. J Sep Sci. 2004 Dec;27(17-18):1379-90. doi: 10.1002/jssc.200401902, PMID 15638147

76. Louie KB, Kosina SM, Hu Y, Otani H, de Raad M, Kuftin AN, et al. 6.12 Mass Spectrometry for Natural Product Discovery. Comprehensive Natural Products III. Amsterdam: Elsevier; 2020. p. 263-306.

77. Yamashita M, Fenn JB. Electrospray ion source: Another variation on the free-jet theme. J Phys Chem. 1984;88(20):4451-9. doi: 10.1021/j150664a002

78. Gupta C, Sarkar D, Tieleman DP, Singharoy A. The ugly, bad, and good stories of large-scale biomolecular simulations. Curr Opin Struct Biol. 2022;73:102338. doi: 10.1016/j.sbi.2022.102338, PMID 35245737

79. Jain S, Pei L, Spraggins JM, Angelo M, Carson JP, Gehlenborg N, et al. Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP). Nat Cell Biol. 2023;25(8):1089-100. doi: 10.1038/s41556- 023-01194-w, PMID 37468756

80. Agbokponto JE, Yemoa LA, Assanhou AG, Liu R, Ganfon H, Ding L. Liquid chromatography tandem mass spectrometry determination method of bencycloquidium bromide: Application to drug interaction study in human. Int J Pharm Pharm Sci. 2021;13(10):43-6. doi: 10.22159/ijpps.2021v13i10.5791

81. Jothula H, Navuluri S, Mulakayala NR. Stability based HPLC method for cyclophosphamide related substances in finished drug products: Development and validation. Int J Curr Pharm Res. 2024;16(3):42-51. doi: 10.22159/ijcpr.2024v16i3.4061

82. Chen H, Yan G, Wen MH, Brooks KN, Zhang Y, Huang PS, et al. Advancements and practical considerations for biophysical research: Navigating the challenges and future of super-resolution microscopy. Chem Biomed Imaging. 2024;2(5):331-44. doi: 10.1021/cbmi.4c00019, PMID 38817319

83. Grebe SK, Singh RJ. LC-MS/MS in the clinical laboratory-where to from here? Clin Biochem Rev. 2011;32(1):5-31. PMID 21451775

84. Pöhö P, Lipponen K, Bespalov MM, Sikanen T, Kotiaho T, Kostiainen R. Comparison of liquid chromatography-mass spectrometry and direct infusion microchip electrospray ionization mass spectrometry in global metabolomics of cell samples. Eur J Pharm Sci. 2019;138:104991. doi: 10.1016/j.ejps.2019.104991, PMID 31404622

85. Nagase K, Nishiyama T, Inoue M, Kanazawa H. Temperature responsive chromatography for therapeutic drug monitoring with an aqueous mobile phase. Sci Rep. 2021 Dec 6;11(1):23508. doi: 10.1038/ s41598-021-02998-2, PMID 34873248

86. Gaspar VP, Ibrahim S, Zahedi RP, Borchers CH. Utility, promise, and limitations of liquid chromatography-mass spectrometry-based therapeutic drug monitoring in precision medicine. J Mass Spectrom. 2021;56(11):e4788. doi: 10.1002/jms.4788, PMID 34738286

87. Kaddah MM, El Demellawy MA, Talaat W. Comprehensive analytical approaches using LC-MS and IC-MS in pharmaceutical and biomedical sciences. Microchem J. 2025;216:114780. doi: 10.1016/j. microc.2025.114780

88. Nakagawa T, Wakui M. LC-MS/MS in clinical diagnostics: Opportunities and implementation challenges. Med J Mass Spectrom. 2025;8:65-73. doi: 10.24508/mms.2024.11.007

89. Espada A, Molina-Martin M, Dage J, Kuo MS. Application of LC/MS and related techniques to high-throughput drug discovery. Drug Discov Today. 2008;13(9-10):417-23. doi: 10.1016/j.drudis.2008.03.005, PMID 18468559

90. Patidar A, Kamble P. A comprehensive review on liquid chromatography-mass spectrometry (LC-MS). Asian J Pharm Res Dev. 2025;13(1):95-103. doi: 10.22270/ajprd.v13i1.1509

91. Kaddah MMY, El Demellawy MA, Talaat W. Comprehensive analytical approaches: The use of LC-MS and IC-MS in modern pharmaceutical and biomedical sciences. Microchem J. 2025;216:114780. doi: 10.1016/j.microc.2025.114780

92. Shareef TH, Mohamed Divan Masood M, Navabshan I. Biochemical evaluation of Indus viva I pulse natural ayurvedic syrup and it’s in silico-interaction analysis. Asian J Pharm Clin Res. 2023;16(12):31-42. doi: 10.22159/ajpcr.2023.v16i12.49266

93. Wong KH, Kwok-Wen NG, Tan BS, Yen-Ping NG, Jing NG. Discovery of photocytotoxic chlorophyll derivatives from Antarctic, Arctic and tropical Chlorella. Asian J Pharm Clin Res. 2025;18(12):136-42. doi: 10.22159/ajpcr.2025v18i12.56970

94. Lee H. Pharmaceutical applications of liquid chromatography coupled with mass spectrometry (LC/MS). J Liq Chromatogr Relat Technol. 2005;28(7-8):1161-202. doi: 10.1081/JLC-200053022

95. Kumar KJ, Vijayan V. An overview of liquid chromatography-mass spectroscopy instrumentation. Pharm Methods. 2014;5(2):47-52. doi: 10.5530/phm.2014.2.2

96. Krokhin O, Li Y, Andonov A, Feldmann H, Flick R, Jones S, et al. Mass spectrometric characterization of proteins from the SARS virus: A preliminary report. Mol Cell Proteomics. 2003;2(5):346-56. doi: 10.1074/mcp.M300048-MCP200, PMID 12775768

97. Gayatri S, Surya M, Karthik R, Vasundra L. Optimization and validation of ultraperformance liquid chromatography coupled with tandem mass spectrometry for quantification of efavirenz in human plasma. Int J Appl Pharm. 2025;17(6):381-7.

98. Akin A, Antosz FJ, Ausec JL, Greve KF, Johnson RL, Magnusson LE, et al. An orthogonal approach to chiral method development screening. Curr Pharm Anal. 2007 Feb 1;3(1):53-70. doi: 10.2174/157341207779802403

99. Stavrianidi A. A classification of liquid chromatography mass spectrometry techniques for evaluation of chemical composition and quality control of traditional medicines. J Chromatogr A. 2020;1609:460501.doi: 10.1016/j.chroma.2019.460501, PMID 31515074

100. Yu Y, Yao C, Guo DA. Insight into chemical basis of traditional Chinese medicine using LC-MS. Acta Pharm Sin B. 2021;11(6):1469- 92. doi: 10.1016/j.apsb.2021.02.017, PMID 34221863

101. Yang M, Sun J, Lu Z, Chen G, Guan S, Liu X, et al. Phytochemical analysis of traditional Chinese medicine using liquid chromatography coupled with mass spectrometry. J Chromatogr A. 2009;1216(11):2045- 62. doi: 10.1016/j.chroma.2008.08.097, PMID 18804769

102. Huang X, Kong L, Li X, Chen X, Guo M, Zou H. Strategy for analysis and screening of bioactive compounds in traditional Chinese medicines. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;812(1-2):71-84. doi: 10.1016/j.jchromb.2004.06.046, PMID 15556489

103. Lee MS, Kerns EH. LC/MS applications in drug development. Mass Spectrom Rev. 1999;18(3-4):187-279. doi: 10.1002/(SICI)1098- 2787(1999)18:3/4<187:AID-MAS2>3.0.CO;2-K, PMID 10568041

104. Lim CK, Lord G. Current developments in LC-MS for pharmaceutical analysis. Biol Pharm Bull. 2002;25(5):547-57. doi: 10.1248/bpb.25.547, PMID 12033491

105. Koehler M, Delguste M, Sieben C, Gillet L, Alsteens D. Initial step of virus entry: Virion binding to cell-surface glycans. Annu Rev Virol. 2020 Sep 29;7(1):143-65. doi: 10.1146/annurev-virology-122019-070025, PMID 32396772

106. Tamara S, den Boer MA, Heck AJ. High-resolution native mass spectrometry. Chem Rev. 2021 Aug 20;122(8):7269-326. doi: 10.1021/acs.chemrev.1c00212, PMID 34415162

107. Barth M, Schmidt C. Native mass spectrometry-a valuable tool in structural biology. J Mass Spectrom. 2020 Oct;55(10):e4578. doi: 10.1002/jms.4578, PMID 32662584

108. Kaur H, Bhagwat SR, Sharma TK, Kumar A. Analytical techniques for characterization of biological molecules-proteins and aptamers/oligonucleotides. Bioanalysis. 2019 Jan 1;11(2):103-17. doi: 10.4155/bio-2018-0225, PMID 30475073

109. Gokul M, Umarani G, Esakki A. Green synthesis and characterization of isolated flavonoid mediated copper nanoparticles by using Thespesia populnea leaf extract and its evaluation of anti-oxidant and anti-cancer activity. Int J Chem Res. 2022 Jan 1;6:15-32. doi: 10.22159/ijcr.2022v6i1.197

Published

07-02-2026

How to Cite

SARAVANAN RAVINDRAN, et al. “LC-MS AS A VERSATILE TOOL FOR DRUG DISCOVERY, DEVELOPMENT, AND CLINICAL DIAGNOSTICS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 19, no. 2, Feb. 2026, pp. 25-35, doi:10.22159/ajpcr.2026v19i2.57475.

Issue

Section

Review Article(s)