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Assessment of pheniramine in alternative biological matrices by liquid chromatography tandem mass spectrometry

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Abstract

Pheniramine is an over-the-counter antihistamine drug. Its accessibility and low cost made it more popular among drug abusers in Pakistan. In this study, pheniramine was quantified in both conventional and alternative specimens of twenty chronic drug abusers, aged 16–50 years, who were positive for pheniramine in comprehensive toxicological screening for drugs by gas chromatography with mass spectral detection in positive electron impact mode. Pheniramine was extracted from biological specimens using solid phase extraction and liquid chromatography tandem mass spectrometry was employed for quantification. Chromatographic separation was carried out on a Poroshell120EC-18 (2.1 mm × 50 mm × 2.7 µm) column using water-acetonitrile in formic acid (0.1%) mobile phase in gradient elution mode with 500 μL/min flow rate. Positive electrospray ionization mode and multi-reaction monitoring with ion transitions m/z 241.3 → 195.8 and 167.1 for pheniramine and m/z m/z 247.6 → 173.1 for pheniramine-d6 were employed. The quantification method showed good linear ranges of 2–1000 ng/mL in blood, urine, and oral fluid; 2–1000 ng/mg in hair and 5–1000 ng/mg in nail with ≥ 0.985% coefficient of linearity. The retention time of pheniramine was 3.0 ± 0.1 min. The detection and lower quantification limits were 1 ng/mL and 2 ng/mL for blood, urine, oral fluid and hair whereas 2.5 ng/mg and 5 ng/mg for nail, respectively. Mean extraction recovery and ionization suppression ranged 86.3–95.1% and -4.6 to -14.4% in the studied matrices. Intra-day and inter-day precision were 4.1–9.3% and 2.8–11.2%, respectively. Pheniramine levels in specimens of drug abusers were 23–480 ng/mL in blood, 72–735 ng/mL in urine, 25–379 ng/mL in oral fluid, 10–170 ng/mg in hair and 8–86 ng/mg in nail specimens. Alternative specimens are of utmost significance in clinical and medico-legal cases. In this study, authors compared matrix-matched calibration curves to blood calibration curve and obtained results within ± 10%; thereby justifying the use of blood calibration curve for urine, oral fluid, hair, and nail specimens.

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Abbreviations

B:

Blood

Cal:

Calibration curve

U:

Urine

OF:

Oral fluid

H:

Hair

N:

Nail

References

  1. Baselt RC. Pheniramine. In: Disposition of toxic drugs and chemicals in man. 12th ed. Seal Beach, CA: Biomedical Publications; 2020. p. 1651–2.

    Google Scholar 

  2. Molina DK. Pheniramine. In Handbook of forensic toxicology for medical examiners. 2nd ed. Boca Raton, FL: CRC Press, Taylor & Francis Group; 2019. p. 178.

    Google Scholar 

  3. Querée EA, Dickson SJ, Missen AW, Pannell LK. Therapeutic and toxic levels of pheniramine in biological specimens. J Anal Toxicol. 1979;3(6):253–5.

    Article  Google Scholar 

  4. Moffat AC, Osselton MD, Widdop B, Watts J. Pheniramine. In: Moffat AC, Osselton MD, Widdop B, Watts J, editors. Clarke’s analysis of drugs and poisons, vol. 2. 4th ed. Pharmaceutical Press. U.K.: London; 2011. p. 1902–3.

    Google Scholar 

  5. Gallardo E, Queiroz JA. The role of alternative specimens in toxicological analysis. Biomed Chromatogr. 2008;22(8):795–821.

    Article  CAS  PubMed  Google Scholar 

  6. Baumgartner WA, Hill VA, Blahd WH. Hair analysis for drugs of abuse. In: advances in analytical toxicology. Chicago, IL: Baselt RC edition. Year Book Medical; 1989. p. 298–329.

    Google Scholar 

  7. Pragst F, Balikova MA. State of the art in hair analysis for detection of drug and alcohol abuse. Clinicachimica acta. 2006;370:17–49.

    Article  CAS  Google Scholar 

  8. Busardò FP, Gottardi M, Pacifici R, Varì MR, Tini A, Volpe AR, Pichini S. Nails analysis for drugs used in the context of chemsex: a pilot study. J Anal Toxicol. 2020;44(1):69–74.

    PubMed  Google Scholar 

  9. Cingolani M, Scavella S, Mencarelli R, Mirtella D, Froldi R, Rodriguez D. Simultaneous detection and quantitation of morphine, 6-acetylmorphine, and cocaine in toenails: comparison with hair analysis. J Anal Toxicol. 2004;28(2):128–31.

    Article  CAS  PubMed  Google Scholar 

  10. Cappelle D, De Keukeleire S, Neels H, Been F, De Doncker M, Dom G, van Nuijs AL. Keratinous matrices for the assessment of drugs of abuse consumption: A correlation study between hair and nails. Drug Test Anal. 2018;10(7):1110–8.

    Article  CAS  Google Scholar 

  11. Krumbiegel F, Hastedt M, Westendorf L, Niebel A, Methling M, Parr MK, Tsokos M. The use of nails as an alternative matrix for the long-term detection of previous drug intake: validation of sensitive UHPLC-MS/MS methods for the quantification of 76 substances and comparison of analytical results for drugs in nail and hair samples. Forensic Sci Med Pathol. 2016;12:416–34.

    Article  CAS  PubMed  Google Scholar 

  12. Spihler V. Drugs in saliva. In: Moffat AC, Osselton MD, Widdop B, Watts J, editors. Clarke’s analysis of drugs and poisons. 4th edition, Volume 1, Chapter 18. London, UK: Pharmaceutical Press; 2011. p. 308–22.

    Google Scholar 

  13. Lachenmeier K, Musshoff F, Madea B. Determination of opiates and cocaine in hair using automated enzyme immunoassay screening methodologies followed by gas chromatographic–mass spectrometric (GC-MS) confirmation. Forensic Sci Int. 2006;159:189–99.

    Article  CAS  PubMed  Google Scholar 

  14. Jones GR. Postmortem toxicology. In: Moffat AC, Osselton MD, Widdop B, Watts J, editors. Clarke’s analysis of drugs and poisons. 4th edition, Volume 1, Chapter 9. London: Pharmaceutical Press; 2011. p. 160–75.

    Google Scholar 

  15. Meyer MR, Maurer HH. Current status of hyphenated mass spectrometry in studies of the metabolism of drugs of abuse, including doping agents. Anal Bioanal Chem. 2012;402:195–208.

    Article  CAS  PubMed  Google Scholar 

  16. Scientific Working Group for Forensic Toxicology. Scientific Working Group for Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. J Anal Toxicol. 2013;37(7):452–74.

    Article  Google Scholar 

  17. Society of Hair Testing. Statement of the Society of Hair Testing concerning the examination of drugs in human hair. Forensic Sci Int. 1997;84:3–6.

    Google Scholar 

  18. Pragst F, Balikova MA. State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chem. 2006;370(1–2):17–49.

    Article  CAS  Google Scholar 

  19. Kuwayama K, Miyaguchi H, Iwata Y, Kanamori T, Tsujikawa K, Yamamuro T, Segawa H, Inoue H. Time-course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products: Time-course measurements of drug concentrations in hair and toenails. Drug Test Anal. 2016;9(4):571–7.

    Article  PubMed  Google Scholar 

  20. Kronstrand R, Andersson MC, Ahlner J, Larson G. Incorporation of selegiline metabolites into hair after oral selegiline intake. J Anal Toxicol. 2001;25(7):594–601.

    Article  CAS  PubMed  Google Scholar 

  21. Kronstrand R, Förstberg-Peterson S, Kagedal B, Ahlner J, Larson G. Codeine concentration in hair after oral administration is dependent on melanin content. Clin Chem. 1999;45(9):1485–94.

    Article  CAS  PubMed  Google Scholar 

  22. Shen M, Chen H, Xiang P. Determination of opiates in human fingernail-comparison to hair. J Chromatogr B. 2014;967:84–9.

    Article  CAS  Google Scholar 

  23. Barbosa J, Faria J, Carvalho F, Pedro M, Queirós O, Moreira R, Dinis-Oliveira RJ. Hair as an alternative matrix in bioanalysis. Bioanalysis. 2013;5(8):895–914.

    Article  CAS  PubMed  Google Scholar 

  24. Palmeri A, Pichini S, Pacifici R, Zuccaro P, Lopez A. Drugs in nails: physiology, pharmacokinetics and forensic toxicology. Clin Pharmacokinet. 2000;38:95–110.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Special thanks to faculty of pharmacy, University of Lahore and clinical and Forensic Toxicology Department, Chughtai Healthcare, Pakistan.

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The submitted study did not receive any grant from the funding agencies in the public, commercial, or not-for-profit sectors.

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All the authors participated equally regarding conceptualization, literature search, analysis, interpretation of results, writing and paper revising.

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Correspondence to Ali Imran Abid.

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The permission was obtained from respondents, participating in this study on an individual consent form. All the participants were also informed about the significance and purpose of the study. Furthermore, the study was also approved by the ethics committee of the University of Lahore. All the procedures performed in the study were in accordance with the ethical standards of the University of Lahore, Pakistan.

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Consent has been obtained from all the participants regarding the publication of this study.

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Makhdoom, H.S., Abid, A.I., Mujahid, M. et al. Assessment of pheniramine in alternative biological matrices by liquid chromatography tandem mass spectrometry. Forensic Sci Med Pathol (2024). https://doi.org/10.1007/s12024-024-00795-7

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