Author(s): Pankaj, Pramod Kumar, Aman Kapoor, Priyanka, Puneet Kumar, Saweta Kumari


DOI: 10.52711/2231-5675.2023.00006   

Address: Pankaj, Pramod Kumar, Aman Kapoor, Priyanka, Puneet Kumar, Saweta Kumari
Dreamz College of Pharmacy, Khilra (Sundernagar) 175036.
*Corresponding Author

Published In:   Volume - 13,      Issue - 1,     Year - 2023

LC-TOF-MS is powerful analytical technique. It is a combination of two techniques one of which is belongs to chromatography and other is from spectroscopy. Chromatography is separation technique and perform both techniques separately it is very time consuming but combined both techniques to save time and provide better results. This represents the potential of liquid chromatography with (quadrupole) time-of-flight mass spectrometry [LC-(Q)TOF-MS] in examining the presence of pesticide metabolites in food and water samples. This method portrays a quick enhanced screen for blood and urine specimens in post-mortem, driving under the influence and drug facilitated sexual assault forensic toxicology casework. (LC–MS) is an analytical technique that amalgamate the physical separation capability of liquid chromatography with the mass analysis capability of mass-spectrometry (MS).This technique can be used in analysis of pharmacokinetics, proteomics/metabolomics, development drug, analysis of pesticides in vegetables, analysis of medicinal panaxherbs for metabolomic research, identification of diphenhydramine in segment sample, investigation of pesticides metabolites in food and water etc.

Cite this article:
Pankaj, Pramod Kumar, Aman Kapoor, Priyanka, Puneet Kumar, Saweta Kumari. LC–Tof-Ms an Influential Hyphenated Technique and its Application. Asian Journal of Pharmaceutical Analysis. 2023; 13(1):35-1. doi: 10.52711/2231-5675.2023.00006

Pankaj, Pramod Kumar, Aman Kapoor, Priyanka, Puneet Kumar, Saweta Kumari. LC–Tof-Ms an Influential Hyphenated Technique and its Application. Asian Journal of Pharmaceutical Analysis. 2023; 13(1):35-1. doi: 10.52711/2231-5675.2023.00006   Available on:

1.    Ferrer, E.M. Thurman (EDITOR), Liquid Chromatography Mass Spectroscopy.
2.    Nagaraju, D Narendra, P Jitendra Kumar, VDN Srinivas, SVN Padma. Determination of Entacapone in Pharmaceutical Preparations by Liquid Chromatography. Asian J. Research Chem. 2(4): Oct.-Dec. 2009 page 454-456.
3.    Meyyanathan. S. N, Babu. B, Kalaivani. M. Development and Validation of An Analytical Liquid Chromatography-Tandem Mass Spectroscopy Method for the Estimation Febuxostat in Pharmaceutical Formulation. Research J. Pharm. and Tech. 2019; 12(5):2137-2140
4.    Sparkman,0. David. Mass Spectroscopy desk Pittsburgh; Global View Pub.
5.    Dubey R.D., Ahmad A.R., Paroha S., Gupta R.K., Sahu P. K., Verma S., Daharwal S. J., Prasad Reddy S.L.N. Mass Spectroscopy: A Versatile Analytical Technique. Research J. Science and Tech. 3(2): March-April. 2011: 55-64.
6.    Downard KM.” Historical account: Francis William Aston: the man behind the mass spectrograph”. European journal of Mass Spectrometry. Prince P “Standard definition of terms relating to mass spectroscopy: A report from the committee on meauserments and standards of the American society for mass spectroscopy” Journal of the American Society of Mass Spectroscopy.
7.    March RE (2000) ”Quadrupole ion trap mass spectroscopy: a view at the turn of the century”. International journal of mass spectroscopy.
8.    Schwartz JC, Senko MW, Syka JE (June 2000).” A two-dimensions quadruple ion trap mass spectrometer. Journal of the American Society Mass Spectrometry.
9.    Pramod K., Amar Deep A., Pooja K., Mahendra Singh A An Overview: LC-MS as Tool of sample Extraction and Quantification in Bioanalytical Laboratories
10.    Khan, Hamid, Javed, Ali. Asian Journal of Pharmaceutical Analysis; Raipur Vol. 7, Iss. 1, (Mar 2017). Identification of Impurities and Degradation Products in Pharmaceutical Products- Role of Hyphenated Techniques
11.    K. Mahendra, Y.L. N. Murthy, C.V. Narasimha Rao, K. Bala Murali Krishna.Quantitative Determination of Solanesol in Tobacco by Liquid Chromatography–Mass Spectrometry (LC-MS). Asian J. Research Chem. 4(7): July, 2011; Page 1125-1130.
12.    Boyd, Robert K. (1994). Linked-scan technique for MS/MS using tandem-in-space instruments. Mass Spectrometry Reviews. 18.Benton HP, Wong DM, Trauger SA, Siuzdak G (August) processing tandem mass spectrometry data metabolite metabolite identification and structural characterization. Analytical Chemistry.
13.    A. Anka Rao, K. Pavan Kumar, A. Narayana Rao, Narender Malothu, B. Prassana Kumar Desu, Naga Raju Bandaru. Rapid Quantitative Estimation of Glipizide and Sitagliptin in Rat Plasma by Liquid Chromatography and Mass spectroscopy (LC-MS). Research Journal of Pharmacy and Technology. 2022; 15(4):1675-9.
14.    Ardey, Robert E. (2003-01-01). “Liquid Chromatography-Mass Spectroscopy: An Introduction Analytical Technique in the Sciences (Ants). john Wiley ans Sons. Ltd
15.    de Hoffmann, Edmond; Stroobant, Vincent (2002). Mass Spectrometry (Principles and Applications) (2nd ed.). Wiley. pp. 157–158. ISBN 0-471-48566-7.
16.    Pitt, James J (February 2009). "Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry". Clin Biochem Rev. 30 (1): 19–34. PMC 2643089. PMID 19224008.
17.    Zhou, Bin; Xiao, Jun Feng; Tuli, Leepika; Ressom, Habtom W (Feb 2012). "LC-MS-based metabolomics". Mol Biosyst. 8 (2): 470–481.
18.    Chaimbault, Patrick (2014-01-01). "The Modern Art of Identification of Natural Substances in Whole Plants". In Jacob, Claus; Kirsch, Gilbert; Slusarenko, Alan; Winyard, Paul G.; Burkholz, Torsten (eds.). Recent Advances in Redox Active Plant and Microbial Products. Springer Netherlands. pp. 31–94.
19.    Dass, Chhabil (2007-01-01). "Hyphenated Separation Techniques". Fundamentals of Contemporary Mass Spectrometry. John Wiley & Sons, Inc. pp. 151–194.
20.    Pitt, James J (2017-03-12). "Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry". The Clinical Biochemist Reviews. (1): 19–34. ISSN 0159-8090. PMC 2643089. PMID 19224008.
21.    Niessen, Wilfried M. A (2006). Liquid Chromatography-Mass Spectrometry, Third Edition. Boca Raton: CRC Taylor & Francis. pp. 50–90. ISBN 9780824740825. OCLC 232370223.
22.    James, A. T.; Martin, A. J. P. (1952-03-01). "Gas-liquid partition chromatography: the separation and micro-estimation of volatile fatty acids from formic acid to dodecanoic acid". Biochemical Journal. 50 (5): 679–690.
23.    Tal'roze, V.L.; Gorodetskii, I.G.; Zolotoy, N.B; Karpov, G.V.; Skurat, V.E.; Maslennikova, V.Ya. (1978). "Capillary system for continuous introducing of volatile liquids into analytical MS and its application". Adv. Mass Spectrom. 7: 858.
24.    Ardrey, Robert E. (2003-01-01). "Introduction". Liquid Chromatography – Mass Spectrometry: An Introduction. Analytical Techniques in the Sciences (Ants). John Wiley & Sons, Ltd. pp. 1–5.
25.    Roberts, Gordon (2013). Roberts, Gordon C. K (ed.). Encyclopaedia of Biophysics – Springer.
26.    Sharp, Thomas R. (2009-01-01). "Mass Spectrometry". In Nassar, Ala F.; Collegiateessor, Paul F. Hollenberg; VP, JoAnn Scatina (eds.). Drug Metabolism Handbook. John Wiley & Sons, Inc. pp. 167–227.
27.    Arpino, Patrick (1992). "Combined liquid chromatography mass spectrometry. Part III. Applications of thermos pray". Mass Spectrometry Reviews. 11 (1): 3–40. Bibcode:1992MSRv...11....3A.
28.    Arpino, Patrick (1989). "Combined liquid chromatography mass spectrometry. Part I. Coupling by means of a moving belt interface". Mass Spectrometry Reviews. 8 (1): 35–55. Bibcode:1989 MSRv....8...35A.
29.    Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. (1989-10-06). "Electrospray ionization for mass spectrometry of large biomolecules". Science. 246 (4926): 64–71. Bibcode:1989Sci...246...64F. CiteSeerX
30.    Sharma Shivani, Singh Navdeep, Ankalgi Amar Deep, Rana Arti, Ashawat Mahendra Singh. A Laconic Review on Liquid Chromatography Mass Spectrometry (LC-MS) Based Proteomics Technology in Drug Discovery. Robb, null; Covey, null; Bruins, null (2000-08-01). "Atmospheric pressure photoionization: an ionization method for liquid chromatography-mass spectrometry". Analytical Chemistry. 72 (15): 3653–3659.
31.    Widmer, Leo; Watson, Stuart; Schlatter, Konrad; Crowson, Andrew (2002). "Development of an LC/MS method for the trace analysis of triacetone triperoxide (TATP)". The Analyst. 127 (12): 16271632. Bibcode:2002Ana...127.1627W.
32.    Jump up to:a b Sudhakar, P.; Latha, P.; Reddy, P. V. (2016-04-05). Phenotyping Crop Plants for Physiological and Biochemical Traits. Academic Press. ISBN 9780128041109.
33.    Horning, E. C.; Horning, M. G.; Carroll, D. I.; Dzidic, I.; Stillwell, R. N. (1973-05-01). "New picogram detection system based on a mass spectrometer with an external ionization source at atmospheric pressure". Analytical Chemistry. 45 (6): 936–943.
34.    Robb, null; Covey, null; Bruins, null (2000-08-01). "Atmospheric pressure photoionization: an ionization method for liquid chromatography-mass spectrometry". Analytical Chemistry. 72 (15): 3653–3659.
35.    Wysocki VH, Resing KA, Zhang Q, Cheng G (2005). "Mass spectrometry of peptides and proteins". Methods. 35 (3): 211–22.
36.    Karlsson, Roger; Thorsell, Annika; Gomila, Margarita; Salvà-Serra, Francisco; Jakobsson, Hedvig E.; Gonzales-Siles, Lucia; Jaén-Luchoro, Daniel; Skovbjerg, Susann; Fuchs, Johannes; Karlsson, Anders; Boulund, Fredrik (2020-03-01). "Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping". Molecular & Cellular Proteomics. 19 (3): 518–528.
37.    Gika, Helen G.; Theodoridis, Georgios A.; Plumb, Robert S.; Wilson, Ian D. (January 2014). "Current practice of liquid chromatography–mass spectrometry in metabolomics and metabonomics". Journal of Pharmaceutical and Biomedical Analysis. 87: 12–25.
38.    Stobiecki, M.; Skirycz, A.; Kerhoas, L.; Kachlicki, P.; Muth, D.; Einhorn, J.; Mueller-Roeber, B. (2006). "Profiling of phenolic glycosidic conjugates in leaves of Arabidopsis thaliana using LC/MS". Metabolomics. 2 (4): 197–219.
39.    Jorge, Tiago F.; Rodrigues, João A.; Caldana, Camila; Schmidt, Romy; van Dongen, Joost T.; Thomas-Oates, Jane; António, Carla (2016-09-01). "Mass spectrometry-based plant metabolomics: Metabolite responses to abiotic stress". Mass Spectrometry Reviews. 35 (5): 620–649. Bibcode:2016MSRv...35..620J.
40.    Tolstikov, Vladimir V.; Fiehn, Oliver (2002). "Analysis of Highly Polar Compounds of Plant Origin: Combination of Hydrophilic Interaction Chromatography and Electrospray Ion Trap Mass Spectrometry". Analytical Biochemistry. 301 (2): 298–307.
41.    Antonio, Carla; Larson, Tony; Gilday, Alison; Graham, Ian; Bergström, Ed; Thomas-Oates, Jane (2008). "Hydrophilic interaction chromatography/electrospray mass spectrometry analysis of carbohydrate-related metabolites from Arabidopsis thaliana leaf tissue". Rapid Communications in Mass Spectrometry. 22 (9): 1399–1407. Bibcode:2008RCMS...22.1399A.
42.    Lee, Mike S.; Kerns, Edward H. (1999). "LC/MS applications in drug development". Mass Spectrometry Reviews. 18 (3–4): 187–279. Bibcode:1999MSRv...18.187L.
43.    Niamh Creedon, Pierre Lovera, Julio Gutierrez Moreno, Michael Nolan, Alan O’Riordan. Highly Sensitive SERS Detection of Neonicotinoid Pesticides. Complete Raman Spectral Assignment of Clothianidin and Imidacloprid. The Journal of Physical Chemistry A 2020, 124 (36), 7238-7247.
44.    Joachim D. Pleil and Matthew A. Stiegel . Evolution of Environmental Exposure Science: Using Breath-Borne Biomarkers for “Discovery” of the Human Exposome. Analytical Chemistry 2013, 85 (21), 9984-9990.
45.    Rajasekaran R., Suresh P. K. Physical and Chemical methods of extraction of Bioactive Molecules from Lepidium sativum Linn. and Antioxidant Activity-based screening and selection of extracts-Probable Phytochemical, Chromatography and mass spectroscopy analysis-based correlates. Research Journal of Pharmacy and Technology. 2021; 14(6):3082-2.
46.    E. Michael Thurman, Imma Ferrer, Paul Zavitsanos, and Jerry A. Zweigenbaum. Analysis of Isobaric Pesticides in Pepper with High-Resolution Liquid Chromatography and Mass Spectrometry: Complementary or Redundant. Journal of Agricultural and Food Chemistry 2013, 61 (10), 2340-2347.
47.    Alberto Angioni, Luciano Porcu, and Filippo Pirisi. LC/DAD/ESI/MS Method for the Determination of Imidacloprid, Thiacloprid, and Spinosad in Olives and Olive Oil after Field Treatment. Journal of Agricultural and Food Chemistry 2011, 59 (20) , 11359-11366.
48.    Feng Li, Jia Lu, and Xiaochao Ma. Profiling the Reactive Metabolites of Xenobiotics Using Metabolomic Technologies. Chemical Research in Toxicology 2011, 24 (5) , 744-751.
49.    Xinyan Bi and Kun-Lin Yang. On-Line Monitoring Imidacloprid and Thiacloprid in Celery Juice Using Quartz Crystal Microbalance. Analytical Chemistry 2009, 81 (2) , 527-532.
50.    Juan F. García-Reyes, Bienvenida Gilbert-López and Antonio Molina-Díaz, Amadeo R. Fernández-Alba. Determination of Pesticide Residues in Fruit-Based Soft Drinks. Analytical Chemistry 2008, 80 (23), 8966-8974.
51.    Justin G. Stroh, Christopher J. Petucci, Scott J. Brecker, Nelson Huang, James M. Lau. Automated sub-ppm mass accuracy on an ESI-TOF for use with drug discovery compound libraries. Journal of the American Society for Mass Spectrometry 2007, 18 (9) , 1612-1616.
52.    Yuqing Yang, Niamh Creedon, Alan O’Riordan, Pierre Lovera. Surface Enhanced Raman Spectroscopy: Applications in Agriculture and Food Safety. Photonics 2021, 8 (12) , 568.
53.    Wei Wu, Chuanxi jiao, Hui Li LC-MS based metabolic and metabonomic studies of, Phytochemical Analysis.
54.    Miao-miao jin, Wei Guo, UPLC-Q-TOF-MS/MS-guided dereplication of Pilsatilla chinensis to identify triterpenoid saponins, Phytochemical Analysis.
55.    European Commission, Guidelines for the generation of data concerning residues as provided in Annex II, part A, section 6, and Annex III, part A, section 8, of Directive 91/414/EEC concerning the placing of plant protection products on the market. Appendix A: Metabolism and Distribution in Plants, Doc 7028/VI/ 95, 22 July 1997 ( resources/app-a.pdf).
56.    European Commission, Regulation (EC) No. 396/2005 on maximum residue levels of pesticides in products of plant and animal origin. Annex II ( protection/pesticides/pesticide_res_annex_ii.xls).
57.    F. Herna´ndez, J.V. Sancho, O.J. Pozo, Rapid Commun. Mass Spectrom. 16 (2002) 1766.
58.    J.V. Sancho, O.J. Pozo, F. Herna´ndez, Analyst (Cambridge, UK) 129 (2004) 38. [5] J.M. Marı´n, J.V. Sancho, O.J. Pozo, F.J. Lo´pez, F. Herna´ndez, J. Chromatogr., A 1133 (2006) 204.
59.    M. Hiemstra, A. de Kok, J. Chromatogr., A 1154 (2007) 3. [7] T. Pihlstrom, G. Blomkvist, P. Friman, U. Pagard, B.G. Osterdahl, Anal. Bioanal. Chem. 389 (2007) 1773. [8] F. Herna´ndez, M. Iba´n˜ ez, O.J. Pozo, J.V. Sancho, J. Mass Spectrom. 43 (2008) 173
60.    Xiaonan Feng, Zongping Wang, Yong Chen, Tao Tao, Feng Wu, and Yuegang Zuo . Effect of Fe (III)/Citrate Concentrations and Ratio on the Photoproduction of Hydroxyl Radicals: Application on the Degradation of Diphenhydramine. Industrial & Engineering Chemistry Research 2012, 51 (20), 7007-7012.
61.    Haiping Hao, Nan Cui, Guangji Wang, Binren Xiang, Yan Liang, Xiangyang Xu, Hui Zhang, Jun Yang, Chaonan Zheng, Liang Wu, Ping Gong and Wei Wang. Global Detection and Identification of Nontarget Components from Herbal Preparations by Liquid Chromatography Hybrid Ion Trap Time-of-Flight Mass Spectrometry and a Strategy. Analytical Chemistry 2008, 80 (21), 8187-8194.
62.    Chunlin Yi, Lihong Song, Qingfeng Wu, Zhaohui Li, Weibin Zhang, Ke Yin. Enhanced photodegradation of diphenhydramine in aqueous solution containing natural sand particles. RSC Advances 2020, 10 (29), 17228-17234.
63.    Jung-Ah Do, Eunyoung Noh, Soon-Byung Yoon, Ji Hyun Lee, Sung-Kwan Park, Suresh Mandava, Sun Young Baek, Jongkook Lee. Collision-induced dissociation pathways of H1-antihistamines by electrospray ionization quadrupole time-of-flight mass spectrometry. Archives of Pharmacal Research 2017, 40 (6).
64.    A. Lagesson, J. Fahlman, T. Brodin, J. Fick, M. Jonsson, P. Byström, J. Klaminder. Bioaccumulation of five pharmaceuticals at multiple trophic levels in an aquatic food web - Insights from a field experiment. Science of The Total Environment 2016, 568 , 208-215.
65.    Polly E. Kintzel, Ting Zhao, Bo Wen, Duxin Sun. Stability of i.v. admixture containing metoclopramide, diphenhydramine hydrochloride, and dexamethasone sodium phosphate in 0.9% sodium chloride injection. American Journal of Health-System Pharmacy 2014, 71 (23) , 2061-2065.
66.    Glicksberg, L., Bryand, K., & Kerrigan, S. (2016). Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry. Journal of Chromatography B, 1035, 91–103.

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