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Counterfeiting honey with phosphodiesterase inhibitors for sexual activity enhancement: detection using high-performance liquid chromatography coupled with a photodiode array detector (HPLC-PAD)

  • Abdullah M. Alkhalaf1
  • Fouza K. Alenazi1
  • Mubarak M. Abudahash1
  • Reem Alfadhli1
  • Ghadah H. Altoum1
  • Naif D. Alenzi1,*,

1Research and Laboratories Sector, National Drug and Cosmetic Control Laboratories (NDCCL), Saudi Food and Drug Authority, P.O Box 7148, 13513 Riyadh, Saudi Arabia

DOI: 10.22514/jomh.2024.057 Vol.20,Issue 4,April 2024 pp.94-103

Submitted: 22 November 2023 Accepted: 20 December 2023

Published: 30 April 2024

*Corresponding Author(s): Naif D. Alenzi E-mail: NDenzi@sfda.gov.sa

Abstract

Globally, there have been several reports of natural products contaminated with illegal adulterants that threaten consumer health because of their adverse pharmacological effects. To treat erectile dysfunction in men, herbal medicine is often adulterated with synthetic phosphodiesterase type 5 (PDE-5) inhibitors. Honey, which is popularly used for its health benefits, is subjected to adulteration with PDE-5 inhibitors. In this study, a rapid and reliable analytical method was proposed to determine the level of adulteration in honey samples. A total of 18 honey samples were tested for the presence of PDE-5 inhibitors (sildenafil, tadalafil and vardenafil) using a high-performance liquid chromatographic method coupled with a photodiode array detector (HPLC-PAD). Chromatography was performed using the Agilent ZORBAX SB-C18 column, with acetonitrile and buffer in the ratio of 1:4 as the mobile phase. Sildenafil, tadalafil and vardenafil reference standards were used for calibration. The retention times of the standards were 21.67, 18.15 and 21.30 min respectively. Of the total samples tested, 55% were positive for PDE-5 inhibitors. Six samples contained sildenafil, three samples contained tadalafil and one sample contained vardenafil. The findings from this study demonstrate that the HPLC-PAD method is suitable and economical for screening PDE-5 inhibitors as adulterants in honey samples marketed for use as sexual activity enhancers. Regular inspections of adulterated products are thus warranted to ensure the safety and health of consumers.


Keywords

Honey; Adulteration; Erectile dysfunction; Phosphodiesterase type 5 inhibitors; Sildenafil; Tadalafil; Vardenafil


Cite and Share

Abdullah M. Alkhalaf,Fouza K. Alenazi,Mubarak M. Abudahash,Reem Alfadhli,Ghadah H. Altoum,Naif D. Alenzi. Counterfeiting honey with phosphodiesterase inhibitors for sexual activity enhancement: detection using high-performance liquid chromatography coupled with a photodiode array detector (HPLC-PAD). Journal of Men's Health. 2024. 20(4);94-103.

References

[1] Standard for Honey. Codex Alimentarius—International food standards. 2001. Available at: https://www.fao.org/3/w0076e/w0076e30.htm (Accessed: 01 September 2023).

[2] Mohd Kamal DA, Ibrahim SF, Kamal H, Kashim MIAM, Mokhtar MH. Physicochemical and medicinal properties of Tualang, Gelam and Kelulut honeys: a comprehensive review. Nutrients. 2021; 13: 197.

[3] Talha M, Imran M, Haseeb Ahmad M, Shabir Ahmad R, Kamran Khan M, Abdul Rahim M, et al. Honey composition, therapeutic potential and authentication through novel technologies: an overview. 1st edn. IntechOpen: United Kingdom. 2023.

[4] Almasaudi S. The antibacterial activities of honey. Saudi Journal of Biological Sciences. 2021; 28: 2188–2196.

[5] Romário-Silva D, Alencar SM, Bueno-Silva B, Sardi JdCO, Franchin M, Carvalho RDPd, et al. Antimicrobial activity of honey against oral microorganisms: current reality, methodological challenges and solutions. Microorganisms. 2022; 10: 2325.

[6] Wadi MA. Antibacterial activity of different global honey samples against standard organisms. Asian Journal of Microbiology, Biotechnology & Environmental Sciences. 2019; 21: 924–930.

[7] Nicewicz AW, Nicewicz Ł, Pawłowska P. Antioxidant capacity of honey from the urban apiary: a comparison with honey from the rural apiary. Scientific Reports. 2021; 11: 9695.

[8] Samarghandian S, Farkhondeh T, Samini F. Honey and health: a review of recent clinical research. Pharmacognosy Research. 2017; 9: 121–127.

[9] Aw Yong PY, Islam F, Harith HH, Israf DA, Tan JW, Tham CL. The potential use of honey as a remedy for allergic diseases: a mini review. Frontiers in Pharmacology. 2021; 11: 599080.

[10] Cilia G, Fratini F, Marchi M, Sagona S, Turchi B, Adamchuk L, et al. Antibacterial activity of honey samples from Ukraine. Veterinary Sciences. 2020; 7:181.

[11] Gallo A. Reprotoxic Impact of Environment, Diet, and Behavior. Int J Environ Res Public Health. 2022; 19(3): 1303.

[12] Dumba K, Kwiringira W, Namukobe J, Ntale M. Identification and analysis of adulterants in aphrodisiac herbal medicines sold by private herbal clinics, pharmacies and herbal drug shops in Kampala, Uganda. East and Central African Journal of Pharmaceutical Sciences. 2021; 24: 3–14.

[13] Atangwho IJ, Ibeneme CE, Egbung GE, Ibeneme E, Eno MA, Nwankpa P. Effect of long-term feeding of the Obudu natural honey and table sugar-sweetened diets on obesity and pro-inflammatory biomarkers in rats. BMC Nutrition. 2020; 6: 3.

[14] Alenezi TM, Ahamed SS, Almutairi HR, Aleisa MF, Alasmari MM, Bagaies AA, et al. Prevalence and the associated factors of erectile dysfunction among Saudi married males. Cureus. 2022; 14: e30998.

[15] Fode M, Wiborg MH, Fojecki G, Joensen UN, Jensen CFS. Organic erectile dysfunction. Ugeskrift for Laeger. 2020; 182: V09190546. (In Danish)

[16] Zaid SSM, Ruslee SS, Mokhtar MH. Protective roles of honey in reproductive health: a review. Molecules. 2021; 26: 3322.

[17] Meo SA, Al-Asiri SA, Mahesar AL, Ansari MJ. Role of honey in modern medicine. Saudi Journal of Biological Sciences. 2017; 24: 975–978.

[18] Banihani SA. Mechanisms of honey on testosterone levels. Heliyon. 2019; 5: e02029.

[19] Wespes E, Amar E, Hatzichristou D, Hatzimouratidis K, Montorsi F, Pryor J, et al. EAU guidelines on erectile dysfunction: an update. European Urology. 2006; 49: 806–815.

[20] Campbell N, Clark JP, Stecher VJ, Thomas JW, Callanan AC, Donnelly BF, Goldstein I, et al. Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors. J Sex Med. 2013; 10(7): 1842-9.

[21] FDA. Tainted honey-based products with hidden active drug ingredients. 2022. Available at: https://www.fda.gov/consumers/health-fraud-scams/tainted-honey-based-products-hidden-active-drug-ingredients (Accessed: 01 September 2023).

[22] Kloner RA, Stanek E, Crowe CL, Singhal M, Pepe RS, Bradsher J, et al. Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors: a retrospective, observational study based on healthcare claims and national death index data. The Journal of Sexual Medicine. 2023; 20: 38–48.

[23] Stridh A, Pontén M, Arver S, Kirsch I, Abé C, Jensen KB. Placebo responses among men with erectile dysfunction enrolled in phosphodiesterase 5 inhibitor trials. JAMA Network Open. 2020; 3: e201423.

[24] Abdelshakour MA, Abdel Salam RA, Hadad GM, Abo-ElMatty DM, Abdel Hameed EA. HPLC-UV and UPLC-MS/MS methods for the simultaneous analysis of sildenafil, vardenafil, and tadalafil and their counterfeits dapoxetine, paroxetine, citalopram, tramadol, and yohimbine in aphrodisiac products. RSC Advances. 2021; 11: 8055–8064.

[25] Saikia Q, Hazarika A, Mishra R. A review on the pharmacological importance of PDE5 and its inhibition to manage biomedical conditions. Journal of Pharmacology and Pharmacotherapeutics. 2022; 13: 246–257.

[26] Abdelmola A, Bahri A, Abuallut I, Refaei B, Hakami W, Abutaleb A, et al. Prevalence, knowledge, and perception about the use of herbal medicines Jazan—Saudi Arabia. Journal of Family Medicine and Primary Care. 2021; 10: 2386.

[27] Barroso F, Ribeiro JC, Miranda EP. Phosphodiesterase type 5 inhibitors and visual side effects: a narrative review. Journal of Ophthalmic and Vision Research. 2021; 29: 248–259.

[28] Gur S, Kadowitz PJ, Gokce A, Sikka SC, Lokman U, Hellstrom WJ. Update on drug interactions with phosphodiesterase-5 inhibitors prescribed as first-line therapy for patients with erectile dysfunction or pulmonary hypertension. Current Drug Metabolism. 2013; 14: 265–269.

[29] Morrisette MJ, Dunn SP. Phosphodiesterase type 5 inhibitors and oral nitrates in male patients with ischemic heart disease. Current Cardiology Reports. 2023; 25: 553–560.

[30] Patel DN, Low W, Tan LL, Tan MB, Zhang Q, Low M, et al. Adverse events associated with the use of complementary medicine and health supplements: an analysis of reports in the Singapore Pharmacovigilance database from 1998 to 2009. Clinical Toxicology. 2012; 50: 481–489.

[31] Amidžić M, Banović Fuentes J, Banović J, Torović L. Notifications and health consequences of unauthorized pharmaceuticals in food supplements. Pharmacy. 2023; 11: 154.

[32] Jairoun AA, Al-Hemyari SS, Shahwan M, Zyoud SH, Ibrahim B, Zyoud SH. Screening and determination of synthetic PDE-5 inhibitors in adulterated sexual enhancement supplements. Molecules. 2022; 27: 6737.

[33] Guo J, Xu Y, Huang Z, He Q, Liu S. Development of an immunoassay for rapid screening of vardenafil and its potential analogues in herbal products based on a group specific monoclonal antibody. Analytica Chimica Acta. 2010; 658: 197–203.

[34] Mans DJ, Callahan RJ, Dunn JD, Gryniewicz-Ruzicka CM. Rapid-screening detection of acetildenafils, sildenafils and avanafil by ion mobility spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 2013; 75: 153–157.

[35] Hu X, Fang G, Han A, Fu Y, Tong R, Wang S. Rapid detection of six phosphodiesterase type 5 enzyme inhibitors in healthcare products using thin‐layer chromatography and surface enhanced Raman spectroscopy combined with BP neural network. Journal of Separation Science. 2017; 40: 2506–2514.

[36] Sacré P, Deconinck E, Chiap P, Crommen J, Mansion F, Rozet E, et al. Development and validation of a ultra-high-performance liquid chromatography-UV method for the detection and quantification of erectile dysfunction drugs and some of their analogues found in counterfeit medicines. Journal of Chromatography a. 2011; 1218: 6439–6447.

[37] Lin YP, Lee YL, Hung CY, Chang CF. Chen Y. Detection of adulterated drugs in traditional Chinese medicine and dietary supplements using hydrogen as a carrier gas. PLoS ONE. 2018; 13(10): e020537.

[38] Strano-Rossi S, Odoardi S, Castrignanò E, Serpelloni G, Chiarotti M. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) determination of stimulants, anorectic drugs and phosphodiesterase 5 inhibitors (PDE5i) in food supplements. Journal of Pharmaceutical and Biomedical Analysis. 2015; 106: 144–152.

[39] Abu Dayyih W, Rasras AA, Hailat M, Karaki R, Deeb AA, Al-Ani I, et al. Determination of five phosphodiesterase-5 inhibitors in multiple honey-based consumer products by chromatographic technique in rat plasma. Processes. 2023; 11: 3019.

[40] Sirhan AY, AlRashdan Y, Abbasi NU, Mostafa A, Abudayeh Z, Talhouni A, et al. Optimization and validation of HPLC-UV method for the determination of vardenafil, sildenafil, and tadalafil in honey-mixed herbal sachets using a design of experiment. Jordan Journal of Pharmaceutical Sciences. 2023; 16: 148–162.

[41] Assemat G, Balayssac S, Gilard V, Martins-Froment N, Fabing I, Rodriguez F, et al. Isolation and identification of ten new sildenafil derivatives in an alleged herbal supplement for sexual enhancement. Journal of Pharmaceutical and Biomedical Analysis. 2020; 191: 113482.

[42] Mokhtar SU, Chin ST, Kee CL, Low MY, Drummer OH, Marriott PJ. Rapid determination of sildenafil and its analogues in dietary supplements using gas chromatography—triple quadrupole mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 2016; 121: 188–196.

[43] Ghramh HA, Khan KA, Zubair A, Ansari MJ. Quality evaluation of Saudi honey harvested from the Asir province by using high-performance liquid chromatography (HPLC). Saudi Journal of Biological Sciences. 2020; 27: 2097–2105.

[44] Abdallah E, Hamed A. Screening for antibacterial activity of two jujube honey samples collected from Saudi Arabia. Journal of Apitherapy. 2019; 5: 6.

[45] Al-Hindi RR, Shehata A. Evaluation of antioxidant and antibacterial activities and essential elements content of locally produced honey in Saudi Arabia. Life Science Journal. 2014; 11: 175–185.

[46] Al-Brahim JS, Mohammed AE. Antioxidant, cytotoxic and antibacterial potentials of biosynthesized silver nanoparticles using bee’s honey from two different floral sources in Saudi Arabia. Saudi Journal of Biological Sciences. 2020; 27: 363–373.

[47] Xiao S, He Y. Analysis of sildenafil in liquor and health wine using surface enhanced Raman spectroscopy. International Journal of Molecular Sciences. 2019; 20: 2722.

[48] Al Lawati HAJ, Al Busaidi I, Kadavilpparampu AM, Suliman FO. Determination of common adulterants in herbal medicine and food samples using core-shell column coupled to tandem mass spectrometry. Journal of Chromatographic Science. 2017; 55: 232–242.

[49] Dural E. Investigation of the presence of sildenafil in herbal dietary supplement by validated HPLC method. Turkish Journal of Pharmaceutical Sciences. 2020; 17: 56–62.

[50] Bujang NB, Chee CF, Heh CH, Rahman NA, Buckle MJC. Phosphodiesterase type 5 inhibitors and their analogs as adulterants of herbal and Food products: analysis of the Malaysian market (2014–2016). Food Additives and Contaminants: Part A. 2017; 34: 1101–1109.

[51] Sifuma SWA, Mwangi JW, Mutai PC, Ongarora DB, Njuguna NM. Evaluation of adulteration of herbal medicine used for treatment of erectile dysfunction in Nairobi county, Kenya. International Journal of Pharmaceutical Sciences Review and Research. 2022; 13: 2095–2100.

[52] Shi S, Wu Y, Zhao M, Cheng Q. Simultaneous analysis of 31 anti-impotence compounds potentially illegally added to herbal-based dietary supplements by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Journal of Chromatography. 2020; 1144: 122077.

[53] Jiru M, Stranska-Zachariasova M, Dzuman Z, Hurkova K, Tomaniova M, Stepan R, et al. Analysis of phosphodiesterase type 5 inhibitors as possible adulterants of botanical-based dietary supplements: extensive survey of preparations available at the Czech market. Journal of Pharmaceutical and Biomedical Analysis. 2019; 164: 713–724.

[54] Wang XB, Zheng J, Li JJ, Yu HY, Li QY, Xu LH, et al. Simultaneous analysis of 23 illegal adulterated aphrodisiac chemical ingredients in health foods and Chinese traditional patent medicines by ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight mass spectrophotometry. Journal of Food and Drug Analysis. 2018; 26: 1138–1153.

[55] National Center for Biotechnology Information. PubChem Compound Summary for CID 135398744, Sildenafil. 2019. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Sildenafil (Accessed: 17 February 2023).


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