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
DOI:
https://doi.org/10.35516/jjps.v16i1.1075Keywords:
HPLC, experiment design, sildenafil, vardenafil, tadalafil, a PDE5 inhibitorAbstract
A method was developed for the simultaneous determination and analysis of sildenafil, vardenafil, and tadalafil in honey-mixed herbal sachets using high-performance liquid chromatography with a UV detector (HPLC–UV). This method eliminates the employment of complex procedures and abolishes time-consuming and labour-intensive pre-treatment processes. In ten minutes, the separation process (at 25oC) of sildenafil, vardenafil, and tadalafil using a C18 150 mm × 4.6 mm x 5 μm column (Shim-pack GIST) was successful with high selectivity and sensitivity. The mobile phase was a 60:40 (v/v) mixture of 0.1 percent formic acid in water and 0.1 percent formic acid in acetonitrile. Using the mobile phase as an extraction mixture, it gave recoveries in the range of 93.0-103.3% at spike levels of 50–150 mg/kg with relative standard deviations (RSDs) lower than 10%. The intra-day and inter-day precision results were in the range of 0.4–0.8% and 1.0–1.7%. Furthermore, the retention times for sildenafil acid, vardenafil acid, and tadalafil were 1.93, 2.47, and 9.62 minutes, respectively, and the limits of detection (LOD) were 1.70, 2.16, and 1.03 mg/L, while the limits of quantification (LOQ) were 5.65, 7.21, and 3.42 mg/L.
References
NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. Jama, 1993. 270(1): p. 83-90.
Montague, D.K., et al., Chapter 1: The management of erectile dysfunction: an AUA update. J Urol, 2005. 174(1): p. 230-9.
Wespes, E., et al., EAU Guidelines on Erectile Dysfunction: An Update. European Urology, 2006. 49(5): p. 806-815.
Elhwuegi, A.S., The Wonders of Phosphodiesterase-5 Inhibitors: A Majestic History. Ann Med Health Sci Res, 2016. 6(3): p. 139-45.
Huang, S.A. and J.D. Lie, Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. PT., 2013; 38(7): p. 407-19.
Limin, M., Johnsen, N.and Hellstrom, W.J. A new rapid-onset phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction. Expert Opin Investig Drugs, 2010. 19(11): p. 1427-37.
Levitra (vardenafil hydrochloride) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; April 2014. 2014.
Stendra (avanafil) package insert. Cranford, NJ: Mist Pharmaceuticals; September 2017.
Viagra (sildenafil citrate) package insert. New York, NY: Pfizer Inc; December 2017.
Cialis (tadalafil) package insert. Indianapolis, IN: Lilly USA, LLC; February 2018.
Red Book Online [Micromedex Solutions; subscription database]. 2018, Greenwood Village, CO: Truven Health Analytics, Inc.
Kotera, J., et al., Avanafil, a potent and highly selective phosphodiesterase-5 inhibitor for erectile dysfunction. J Urol, 2012. 188(2): p. 668-74.
Omori, K. and J. Kotera, Overview of PDEs and their regulation. Circ Res, 2007. 100(3): p. 309-27.
Viagra (sildenafil), prescribing information. New York: Pfizer; Jan, 2010.
Levitra (vardenafil), prescribing information. Wayne, N.J.: Bayer Healthcare/GlaxoSmithKline; revised November, 2011.
Cialis (tadalafil), prescribing information. Indianapolis, Ind.: Eli Lilly; Oct, 2011.
Carrier, S., Pharmacology of phosphodiesterase 5 inhibitors. Can J Urol, 2003. 10 Suppl 1: p. 12-6.
Abdelshakour, M.A., et al., 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(14): p. 8055-8064.
Mustabasic, N. and Isik,S. Determination of sildenafil mixed into herbal honey mixture by ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry. Croatian Journal of Food Science and Technology, 2017. 9: p. 168-172.
Dural, E., Investigation of the Presence of Sildenafil in Herbal Dietary Supplements by Validated HPLC Method. Turk J Pharm Sci, 2020. 17(1): p. 56-62.
Al-Tahami, K., Determination of sildenafil, vardenafil and tadalafil in dietary supplements sold in the Yemeni market. IJSR - International Journal of Scientific Research, 2014. 3(4): p. 403-405.
Jiru, M., 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: p. 713-724.
Dural, E., Investigation of the Presence of Sildenafil in Herbal Dietary Supplements by Validated HPLC Method. Turkish journal of pharmaceutical sciences, 2020. 17(1): p. 56-62.
Soubra, R., et al., Identification And Quantification of Phosphodiesterase-5 Inhibitors As Adulterants In Dietary Supplements Marked For Sexual Enhancement In The Lebanese Market. International Journal of Pharmacy and Pharmaceutical Sciences, 2020. 12(3): p. 57-62.
Kamaruzaman, N.A., et al., Determination of Phosphodiesterase Type 5 Enzyme (PDE-5) Inhibitors and Analogues as Adulterants in Selected Herbal Products using Gas Chromatography–Electron Impact-Mass Spectrometer (GC-EI-MS). Baghdad Science Journal, 2020. 17(4): p. 1190.
Doi, T., et al., Characterization of a new illicit phosphodiesterase-type-5 inhibitor identified in the softgel shell of a dietary supplement. J Pharm Biomed Anal, 2018. 161: p. 61-65.
Gan, K.Z., et al., Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Vardenafil and Its Application of Bioequivalence. International Journal of Analytical Chemistry, 2021. 2021: p. 5590594.
Jeong, J.H., et al., LC-ESI-MS/MS analysis of phosphodiesterase-5 inhibitors and their analogues in foods and dietary supplements in Korea. Food Addit Contam Part B Surveill, 2016. 9(1): p. 1-8.
Alzweiri, M., K. Sweidan, and Q. Aqel, Investigation of the Chemical Stability of Lenalidomide in Methanol/Ethanol Solvents Using RP-HPLC-UV and LC-MS. Jordan j. pharm.sci., 2022. 15(3): p. 305-314.
Tutunji, L., et al., Determination of Cefdinir in Human Plasma using HPLC Coupled with Tandem Mass Spectroscopy: Application to Bioequivalence Studies. Jordan j. pharm. sci., 2015. 8(2): p. 123-139.
Sirhan, A.Y., et al., An QuEChERS -HPLC Method for Aflatoxin Detection of Domestic and Imported Food in Jordan Food and Chemical Toxicology, 2014.
Nickum, E.A. and C.L. Flurer, Determination of Phosphodiesterase-5 Inhibitors and Analogs Using High-Performance Liquid Chromatography with Ultraviolet Detection. Journal of Chromatographic Science, 2014. 53(1): p. 38-46.
Yasmeen, H.M., A Simple Spectrophotometric Assay of Sildenafil In Pure and Pharmaceutical Preparations. Al-Nahrain Journal of Science, 2018. 15(1).
Zhu, X., et al., Simultaneous determination of sildenafil, vardenafil and tadalafil as forbidden components in natural dietary supplements for male sexual potency by high-performance liquid chromatography-electrospray ionization mass spectrometry. Journal of chromatography. A, 2005. 1066(1-2): p. 89-95.
Shabir, G.A., Validation of high-performance liquid chromatography methods for pharmaceutical analysis: Understanding the differences and similarities between validation requirements of the US Food and Drug Administration, the US Pharmacopeia and the International Conference on Harmonization. Journal of Chromatography A, 2003. 987(1): p. 57-66.
