Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy

Fulin Jiang; Jingyu Liu; Yagang Li; Zihan Lu; Qian Liu; Yunhui Xing; Janshon Zhu; Min Huang; Guoping Zhong

doi:10.1016/j.jpha.2024.02.008

Volume 14 Issue 7

Jul. 2024

Turn off MathJax

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(7): 100954

Fulin Jiang, Jingyu Liu, Yagang Li, Zihan Lu, Qian Liu, Yunhui Xing, Janshon Zhu, Min Huang, Guoping Zhong. Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy[J]. Journal of Pharmaceutical Analysis, 2024, 14(7): 100954. doi: 10.1016/j.jpha.2024.02.008

Citation:

Fulin Jiang, Jingyu Liu, Yagang Li, Zihan Lu, Qian Liu, Yunhui Xing, Janshon Zhu, Min Huang, Guoping Zhong. Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy[J]. Journal of Pharmaceutical Analysis, 2024, 14(7): 100954. doi: 10.1016/j.jpha.2024.02.008

Citation:

Fulin Jiang, Jingyu Liu, Yagang Li, Zihan Lu, Qian Liu, Yunhui Xing, Janshon Zhu, Min Huang, Guoping Zhong. Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy[J]. Journal of Pharmaceutical Analysis, 2024, 14(7): 100954. doi: 10.1016/j.jpha.2024.02.008

PDF( 3439 KB)

Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy

doi: 10.1016/j.jpha.2024.02.008

a. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510080, China;
b. Guangdong RangerBio Technologies Co., Ltd., Dongguan, Guangdong, 523000, China

Funds:

The authors appreciate the financial support provided by the National Natural Science Foundation of China (Grant No.: 82173776), Natural Science Foundation of Guangdong Province, China (Grant No.: 2021A1515010574), and Guangdong Basic and Applied Basic Research Foundation, China (Grant No.: 2021A1515110346).

Received Date: Nov. 05, 2023
Accepted Date: Feb. 21, 2024
Rev Recd Date: Jan. 06, 2024
Publish Date: Feb. 24, 2024

Abstract

Abstract

Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS) is a widely utilized technique for in vivo pharmaceutical analysis. Ionization interference within electrospray ion source, occurring between drugs and metabolites, can lead to signal variations, potentially compromising quantitative accuracy. Currently, method validation often overlooks this type of signal interference, which may result in systematic errors in quantitative results without matrix-matched calibration. In this study, we conducted an investigation using ten different groups of drugs and their corresponding metabolites across three LC-ESI-MS systems to assess the prevalence of signal interference. Such interferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites, thereby altering the relationship between analyte response and concentration for quantification. Finally, we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods: chromatographic separation, dilution, and stable labeled isotope internal standards correction. The above strategies were integrated into the method establishment process to improve quantitative accuracy.
- Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS),
- Drugs,
- Metabolites,
- Ionization interference,
- Quantitative analysis

FullText(HTML)

References(39)

References

[1]	S.N. Thomas, D. French, P.J. Jannetto, et al., Liquid chromatography-tandem mass spectrometry for clinical diagnostics, Nat. Rev. Meth. Primers 2 (2022), 96.
[2]	P. Turnpenny, A. Dickie, J. Malec, et al., Retention-directed and selectivity controlled chromatographic resolution: Rapid post-hoc analysis of DMPK samples to achieve high-throughput LC-MS separation, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1164 (2021), 122514.
[3]	A. Nasiri, R. Jahani, S. Mokhtari, et al., Overview, consequences, and strategies for overcoming matrix effects in LC-MS analysis: A critical review, Analyst 146 (2021) 6049-6063.
[4]	A. Furey, M. Moriarty, V. Bane, et al., Ion suppression; a critical review on causes, evaluation, prevention and applications, Talanta 115 (2013) 104-122.
[5]	FDA, M10 Bioanalytical Method Validation and Study Sample Analysis. Editor, Book M10 Bioanalytical Method Validation and Study Sample Analysis, Series M10 Bioanalytical Method Validation and Study Sample Analysis, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/m10-bioanalytical-method-validation-and-study-sample-analysis, 2022.
[6]	FDA, Bioanalytical Method Validation Guidance for Industry. Editor, Book Bioanalytical Method Validation Guidance for Industry, Series Bioanalytical Method Validation Guidance for Industry, 2018. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioanalytical-method-validation-guidance-industry.
[7]	Z. Yan, N. Maher, R. Torres, et al., Isobaric metabolite interferences and the requirement for close examination of raw data in addition to stringent chromatographic separations in liquid chromatography/tandem mass spectrometric analysis of drugs in biological matrix, Rapid Commun. Mass Spectrom. 22 (2008) 2021-2028.
[8]	A. Gonel, I. Kirhan, I. Koyuncu, et al., The role of interferences in the increasing incidence of vitamin D deficiency, Endocr. Metab. Immune Disord. Drug Targets 20 (2020) 1303-1308.
[9]	Y. Cheung, S.J. Ray, A.J. Schwartz, et al., Use of gradient dilution to detect and correct matrix interferences in inductively coupled plasma-time-of-flight mass spectrometry (ICP-TOFMS), Appl. Spectrosc. 70 (2016) 1797-1805.
[10]	M.L. Oldekop, R. Rebane, K. Herodes, Dependence of matrix effect on ionization polarity during LC-ESI-MS analysis of derivatized amino acids in some natural samples, Eur. J. Mass Spectrom. (Chichester) 23 (2017) 245-253.
[11]	X. He, J. Gabler, C. Yuan, et al., Quantitative measurement of plasma free metanephrines by ion-pairing solid phase extraction and liquid chromatography-tandem mass spectrometry with porous graphitic carbon column, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 879 (2011) 2355-2359.
[12]	L. Hu, L. Ding, X. Li, et al., Interference by metabolites and the corresponding troubleshooting during the LC-MS/MS bioanalysis of G004, a bromine-containing hypoglycemic agent, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 899 (2012) 8-13.
[13]	Q. Liu, F. Jiang, J. Zhu, et al., Development, validation, and application of a new method to correct the nonlinearity problem in LC-MS/MS quantification using stable isotope-labeled internal standards, Anal. Chem. 91 (2019) 9616-9622.
[14]	S. Tisler, D.I. Pattison, J.H. Christensen, Correction of matrix effects for reliable non-target screening LC-ESI-MS analysis of wastewater, Anal. Chem. 93 (2021) 8432-8441.
[15]	Z. Wei, S. Han, X. Gong, et al., Rapid removal of matrices from small-volume samples by step-voltage nanoelectrospray, Angew. Chem. Int. Ed Engl. 52 (2013) 11025-11028.
[16]	P.L. Clemens, J.C. Cloyd, R.L. Kriel, et al., Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension, Clin. Drug Investig. 27 (2007) 243-250.
[17]	D.W. Kim, N. Gu, I.J. Jang, et al., Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy, Epilepsia 53 (2012) e9-e12.
[18]	B.J. Steinhoff, Oxcarbazepine extended-release formulation in epilepsy, Expert Rev. Clin. Pharmacol. 2 (2009) 155-162.
[19]	Q. Yang, Y. Li, J.-D. Yang, et al., Holistic prediction of the pKa in diverse solvents based on a machine-learning approach, Angew. Chem. Int. Ed Engl. 59 (2020) 19282-19291.
[20]	N.B. Cech, C.G. Enke, Relating electrospray ionization response to nonpolar character of small peptides, Anal. Chem. 72 (2000) 2717-2723.
[21]	R. Kostiainen, T.J. Kauppila, Effect of eluent on the ionization process in liquid chromatography-mass spectrometry, J. Chromatogr. A 1216 (2009) 685-699.
[22]	A. Kruve, Influence of mobile phase, source parameters and source type on electrospray ionization efficiency in negative ion mode, J. Mass Spectrom. 51 (2016) 596-601.
[23]	J. Liigand, A. Kruve, I. Leito, et al., Effect of mobile phase on electrospray ionization efficiency, J. Am. Soc. Mass Spectrom. 25 (2014) 1853-1861.
[24]	E.T. Gangl, M.M. Annan, N. Spooner, et al., Reduction of signal suppression effects in ESI-MS using a nanosplitting device, Anal. Chem. 73 (2001) 5635-5644.
[25]	P.W. Carr, X. Wang, D.R. Stoll, Effect of pressure, particle size, and time on optimizing performance in liquid chromatography, Anal. Chem. 81 (2009) 5342-5353.
[26]	C. Galitzine, J.D. Egertson, S. Abbatiello, et al., Nonlinear regression improves accuracy of characterization of multiplexed mass spectrometric assays, Mol. Cell. Proteomics 17 (2018) 913-924.
[27]	P.N. Patsalos, D.J. Berry, B.F.D. Bourgeois, et al., Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies, Epilepsia 49 (2008) 1239-1276.
[28]	M. Leclercq, O. Mathieu, E. Gomez, et al., Presence and fate of carbamazepine, oxcarbazepine, and seven of their metabolites at wastewater treatment plants, Arch. Environ. Contam. Toxicol. 56 (2009) 408-415.
[29]	H. Breton, M. Cociglio, F. Bressolle, et al., Liquid chromatography-electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 828 (2005) 80-90.
[30]	C. Dicaire, E.R. Berube, I. Dumont, et al., Impact of oxcarbazepine sulfate metabolite on incurred sample reanalysis and quantification of oxcarbazepine, Bioanalysis 3 (2011) 973-982.
[31]	G. Corso, O. D’Apolito, G. Paglia, The accuracy of oxcarbazepine (OXC) quantification by a liquid chromatography/tandem mass spectrometry method is influenced by the ion source fragmentation of its metabolite trans-diol-carbazepine (DHD), Rapid Commun. Mass Spectrom. 21 (2007) 269-272.
[32]	L. Ouerdane, J. Meija, S. Bakirdere, et al., Nonlinear signal response in electrospray mass spectrometry: Implications for quantitation of arsenobetaine using stable isotope labeling by liquid chromatography and electrospray Orbitrap mass spectrometry, Anal. Chem. 84 (2012) 3958-3964.
[33]	S. Wang, M. Cyronak, E. Yang, Does a stable isotopically labeled internal standard always correct analyte response? A matrix effect study on a LC/MS/MS method for the determination of carvedilol enantiomers in human plasma, J. Pharm. Biomed. Anal. 43 (2007) 701-707.
[34]	W. Jian, R.W. Edom, Y. Xu, et al., Potential bias and mitigations when using stable isotope labeled parent drug as internal standard for LC-MS/MS quantitation of metabolites, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 878 (2010) 3267-3276.
[35]	H.R. Liang, R.L. Foltz, M. Meng, et al., Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable-isotope-labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry, Rapid Commun. Mass Spectrom. 17 (2003) 2815-2821.
[36]	W. Li, H. Lin, J. Flarakos, et al., Practical approaches to incurred sample LC-MS/MS reanalysis: Confirming unexpected results, Anal. Chem. 85 (2013) 2405-2413.
[37]	J. Favresse, M.C. Burlacu, D. Maiter, et al., Interferences with thyroid function immunoassays: Clinical implications and detection algorithm, Endocr. Rev. 39 (2018) 830-850.
[38]	J.F. Emerson, G. Ngo, S.S. Emerson, Screening for interference in immunoassays, Clin. Chem. 49 (2003) 1163-1169.
[39]	M.L. Oldekop, K. Herodes, R. Rebane, Study of the matrix effects and sample dilution influence on the LC-ESI-MS/MS analysis using four derivatization reagents, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 967 (2014) 147-155.