FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Rapid communications in mass spectrometry : RCM2023; 37(14); e9530; doi: 10.1002/rcm.9530

Electrospray ionization mass spectrometry adduct formation by mobile phase additives: A case study using nitrile functional groups containing selective androgen receptor modulators.

Abstract: The formation of mass adducts is common during electrospray ionization mass spectrometry (ESI-MS). However, the mechanism that leads to adduct formation is poorly understood and difficult to control. Multiplication of mass adducts at once will adversely impact the sensitivity of mass analysis and cause misinterpretation of the level of detection. Prior studies on selective androgen receptor modulators (SARMs) revealed an immense mass adduct formation in both positive and negative ESI modes. Methods: In this study, additives in the mobile phases are investigated as a potential means of controlling mass adduct formation in various SARMs. Results: The first evidence of chloride adduct formation when SARMs are detected via ESI-MS has been reported in this research. A series of mobile phase combinations were tested to achieve the optimal condition for HPLC-MS. A comparison was also made between adduct formation on various grades of water used for preparing the mobile phase. A validation study using equine urine and plasma was also conducted to assess the suitability of the developed method. Conclusions: The results of this study will allow for a more accurate identification of SARMs, which will make it easier to investigate their illicit use in horse racing.
© 2023 John Wiley & Sons Ltd.
Get Full Text
Publication Date: 2023-05-01 PubMed ID: 37125537DOI: 10.1002/rcm.9530Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper focuses on the understanding and control of mass adduct formation during electrospray ionization mass spectrometry (ESI-MS), a phenomenon that can negatively impact analysis results. The study further examines the effect of additives in the mobile phases on adduct formation in selective androgen receptor modulators (SARMs) and presents a method to more accurately identify such compounds, which can find use in investigations into illegal horse racing activities.

Understanding Mass Adduct Formation

  • During the process of electrospray ionization mass spectrometry (ESI-MS), mass adducts – complex molecules resulting from the union of two or more simpler ones – often form. This is a common occurrence, yet its mechanism is not fully understood and poses challenges in control.
  • The multiplicity of mass adducts being formed simultaneously does affect the sensitivity of the mass analysis carried out, posing difficulties in detecting and interpreting results.
  • Particular interest in this study was directed at selective androgen receptor modulators or SARMs, a class of drugs with effects similar to anabolic steroids. Past studies have shown significant mass adduct formation involving these compounds, with ESI-MS used in both positive and negative modes.

Role of Mobile Phase Additives

  • Mobile phases, the liquid solution used in chromatographic techniques to carry the sample through the system, often include additives which can interact with the compounds of interest.
  • This study explored these additives as potential factors that might influence mass adduct formation in SARMs.
  • The research also provided the first-ever evidence of chloride adduct formation when SARMs are analyzed through ESI-MS.

Optimization and Validation

  • A series of mobile phase combinations was tested in order to arrive at the optimal conditions for High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS), a widely-used technique in analytical chemistry.
  • A comparison among different grades of water, used in preparation of mobile phases, was made to evaluate the effect on adduct formation.
  • A practical application of the developed methodology was tested through a validation study on equine urine and plasma samples. This is notably relevant as SARMs are occasionally used illicitly in horse racing to enhance performance.

Conclusion

  • The findings of this research could enhance the accuracy of identifying SARMs, thereby facilitating investigations into illegal use in horse racing.

Cite This Article

APA
Karatt TK, Muhammed Ajeebsanu M, Karakka Kal AK, Subhahar MB, Sathiq MA, Laya S. (2023). Electrospray ionization mass spectrometry adduct formation by mobile phase additives: A case study using nitrile functional groups containing selective androgen receptor modulators. Rapid Commun Mass Spectrom, 37(14), e9530. https://doi.org/10.1002/rcm.9530

Publication

Rapid communications in mass spectrometry : RCM
ISSN: 1097-0231
NlmUniqueID: 8802365
Country: England
Language: English
Volume: 37
Issue: 14
Pages: e9530

Researcher Affiliations

Karatt, Tajudheen Kunhamu
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
  • Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tiruchirappalli, India.
Muhammed Ajeebsanu, Meleparappil
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Karakka Kal, Abdul Khader
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Subhahar, Michael Benedict
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Sathiq, Mohamedkhani Anwar
  • Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tiruchirappalli, India.
Laya, Saraswathy
  • Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.

MeSH Terms

  • Animals
  • Horses
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Receptors, Androgen
  • Chromatography, High Pressure Liquid / methods
  • Indicators and Reagents
  • Androgens

Grant Funding

  • DST-FIST Funded PG
  • Research Department of Chemistry and the management committee of Jamal Mohamed College, Tiruchirapalli 620020

References

This article includes 48 references
  1. Schug K, McNair HM. Adduct formation in electrospray ionization mass spectrometry II. Benzoic acid derivatives.. J Chromatogr A 2003;985(1-2):531-539.
  2. Schug K, McNair HM. Adduct formation in electrospray ionization. Part 1: common acidic pharmaceuticals.. J Sep Sci 2002;25:760-766.
  3. Erngren I, Haglöf J, Engskog MKR. Adduct formation in electrospray ionisation-mass spectrometry with hydrophilic interaction liquid chromatography is strongly affected by the inorganic ion concentration of the samples.. J Chromatogr A 2019;1600:174-182.
  4. Kruve A, Kaupmees K. Adduct formation in ESI-MS by mobile phase additives.. J Am Soc Mass Spectrom 2017;28(5):887-894.
  5. Steckel A, Schlosser G. An organic chemist's guide to electrospray mass spectrometric structure elucidation.. Molecules 2019;24(3):611.
    doi: 10.3390/molecules24030611google scholar: lookup
  6. Weissberg A, Dagan S. Interpretation of ESI (+)-MS-MS spectra-towards the identification of “unknowns”.. Int J Mass Spectrom 2011;299:158-168.
  7. Demarque DP, Crotti AE, Vessecchi R, Lopes JL, Lopes NP. Fragmentation reactions using electrospray ionization mass spectrometry: an important tool for the structural elucidation and characterization of synthetic and natural products.. Nat Prod Rep 2016;33(3):432-455.
  8. Kind T, Fiehn O. Seven golden rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry.. BMC Bioinformatics 2007;8:105.
  9. Raffaelli A, Saba A. Atmospheric pressure photoionization mass spectrometry.. Mass Spectrom Rev 2003;22(5):318-331.
  10. Sleno L, Volmer DA. Ion activation methods for tandem mass spectrometry.. J Mass Spectrom 2004;39(10):1091-1112.
  11. Zubarev RA, Horn DM, Fridriksson EK. Electron capture dissociation for structural characterization of multiply charged protein cations.. Anal Chem 2000;72(3):563-573.
  12. Zhao JJ, Yang AY, Rogers JD. Effects of liquid chromatography mobile phase buffer contents on the ionization and fragmentation of analytes in liquid chromatographic/ionspray tandem mass spectrometric determination.. J Mass Spectrom 2002;37(4):421-433.
  13. Liigand J, Kruve A, Leito I, Girod M, Antoine R. Effect of mobile phase on electrospray ionization efficiency.. J Am Soc Mass Spectrom 2014;25(11):1853-1861.
  14. Gao S, Zhang ZP, Karnes HT. Sensitivity enhancement in liquid chromatography/atmospheric pressure ionization mass spectrometry using derivatization and mobile phase additives.. J Chromatogr B Analyt Technol Biomed Life Sci 2005;825(2):98-110.
  15. Mathis JA, McCord BR. The analysis of high explosives by liquid chromatography/electrospray ionization mass spectrometry: multiplexed detection of negative ion adducts.. Rapid Commun Mass Spectrom 2005;19(2):99-104.
  16. Oss M, Kruve A, Herodes K, Leito I. Electrospray ionization efficiency scale of organic compounds.. Anal Chem 2010;82(7):2865-2872.
  17. Murray K, Boyd R, Eberlin M, Langley G, Li L, Naito Y. Definitions of terms relating to mass spectrometry (IUPAC recommendations 2013).. Pure Appl Chem 2013;85(7):1515-1609.
  18. Qi BL, Liu P, Wang QJ, Cai WJ, Yuan BF, Feng YQ. Derivatization for liquid chromatography-mass spectrometry.. Trends Anal Chem 2014;59:121-132.
  19. Cech NB, Enke CG. Practical implications of some recent studies in electrospray ionization fundamentals.. Mass Spectrom Rev 2001;20(6):362-387.
  20. Enke CG. A predictive model for matrix and analyte effects in electrospray ionization of singly-charged ionic analytes.. Anal Chem 1997;69(23):4885-4893.
  21. Kruve A, Kaupmees K, Liigand J, Leito I. Negative electrospray ionization via deprotonation: predicting the ionization efficiency.. Anal Chem 2014;86(10):4822-4830.
  22. Kruve A, Kaupmees K, Liigand J, Oss M, Leito I. Sodium adduct formation efficiency in ESI source.. J Mass Spectrom 2013;48(6):695-702.
  23. Pegram LM, Record MT Jr. Quantifying accumulation or exclusion of H+, HO-, and Hofmeister salt ions near interfaces.. Chem Phys Lett 2008;467(1-3):1-8.
  24. Li XF, Ma M, Scherban K, Tam YK. Liquid chromatography-electrospray mass spectrometric studies of ginkgolides and bilobalide using simultaneous monitoring of proton, ammonium and sodium adducts.. Analyst 2002;127(5):641-646.
  25. Tse YL, Chen C, Lindberg GE, Kumar R, Voth GA. Propensity of hydrated excess protons and hydroxide anions for the air-water Interface.. J Am Chem Soc 2015;137(39):12610-12616.
  26. Griffiths WJ. Tandem mass spectrometry in the study of fatty acids, bile acids, and steroids.. Mass Spectrom Rev 2003;22(2):81-152.
  27. Hao C, Lissemore L, Nguyen B, Kleywegt S, Yang P, Solomon K. Determination of pharmaceuticals in environmental waters by liquid chromatography/electrospray ionization/tandem mass spectrometry.. Anal Bioanal Chem 2006;384(2):505-513.
  28. Thurman EM, Ferrer I, Pozo OJ, Sancho JV, Hernandez F. The even-electron rule in electrospray mass spectra of pesticides.. Rapid Commun Mass Spectrom 2007;21(23):3855-3868.
  29. Pittenauer E, Allmaier G. The renaissance of high-energy CID for structural elucidation of complex lipids: MALDI-TOF/RTOF-MS of alkali cationized triacylglycerols.. J Am Soc Mass Spectrom 2009;20(6):1037-1047.
  30. Karatt TK, Sathiq MA, Laya S, Philip M, Karakka Kal AK, Subhahar MB. Investigation of in vitro generated metabolites of GLPG0492 using equine liver microsomes for doping control.. Drug Test Anal 2023;1-24.
    doi: 10.1002/dta.3453google scholar: lookup
  31. Subhahar MB, Karakka Kal AK, Philip M. Detection and identification of ACP-105 and its metabolites in equine urine using LC-MS/MS after oral administration.. Drug Test Anal 2021;13(2):299-317.
  32. Karatt TK, Sathiq MA, Laya S. Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control.. Rapid Commun Mass Spectrom 2023;37(9):e9491.
    doi: 10.1002/rcm.9491google scholar: lookup
  33. Karatt TK, Sathiq MA, Laya S. In-depth metabolic study of nonsteroidal selective androgen receptor modulator GSK2881078 in thoroughbred horses and horse liver microsomes for doping control.. Drug Test Anal 2023;1-12.
    doi: 10.1002/dta.3469google scholar: lookup
  34. Stacchini C, Botrè F, Comunità F. Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques.. J Pharm Biomed Anal 2021;195:113849.
  35. Cutler C, Viljanto M, Taylor P. Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration.. Drug Test Anal 2021;13(2):369-385.
  36. Schlienger N, Lund BW, Pawlas J. Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators.. J Med Chem 2009;52(22):7186-7191.
  37. Miller CP, Shomali M, Lyttle CR. Design, synthesis, and preclinical characterization of the selective androgen receptor modulator (SARM) RAD140.. ACS Med Chem Lett 2010;2(2):124-129.
  38. Yi P, Rehmel JF, Cassidy K. Disposition and metabolism of LY2452473, a selective androgen receptor modulator, in humans.. Drug Metab Dispos 2012;40(12):2354-2364.
  39. Bhattacharya I, Tarabar S, Liang Y, Pradhan V, Owens J, Oemar B. Safety, pharmacokinetic, and pharmacodynamic evaluation after single and multiple ascending doses of a novel selective androgen receptor modulator in healthy subjects.. Clin Ther 2016;38(6):1401-1416.
  40. Nique F, Hebbe S, Triballeau N. Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen receptor modulator.. J Med Chem 2012;55(19):8236-8247.
  41. Basaria S, Collins L, Dillon EL. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.. J Gerontol A Biol Sci Med Sci 2013;68(1):87-95.
  42. Clark RV, Walker AC, Andrews S, Turnbull P, Wald JA, Magee MH. Safety, pharmacokinetics and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women.. Br J Clin Pharmacol 2017;83(10):2179-2194.
  43. Mohler ML, Bohl CE, Jones A. Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit.. J Med Chem 2009;52(12):3597-3617.
  44. Cockshott ID. Bicalutamide: clinical pharmacokinetics and metabolism.. Clin Pharmacokinet 2004;43(13):855-878.
  45. Karakka Kal AK, Karatt TK, Nalakath J. Simultaneous analysis of 44 frequently abused corticosteroid drugs using polysaccharide-based chiral column-HRMS approach.. Anal Sci Adv 2021;2:427-439.
  46. Ventura E, Gadaj A, Buckley T, Mooney MH. Development of a multi-residue high-throughput UHPLC-MS/MS method for routine monitoring of SARM compounds in equine and bovine blood.. Drug Test Anal 2020;12(9):1373-1379.
  47. Karakka Kal AK, Karatt TK, Philip M, Samir M, Nalakath J. Separation and determination of the enantiomeric levamisole and dexamisole in equine plasma samples using chiral polysaccharide column/LC-MS/MS.. Curr Anal Chem 2020;16(6):761-767.
  48. Ventura E, Gadaj A, Monteith G. Development and validation of a semi-quantitative ultra-high performance liquid chromatography-tandem mass spectrometry method for screening of selective androgen receptor modulators in urine.. J Chromatogr A 2019;1600:183-196.

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.