Chemical Fingerprinting of Counterfeits of Viagra and Cialis Tablets and Analogues via Electrospray Ionization Mass Spectrometry

Abstract

Direct infusion electrospray ionization mass spectrometry (ESI-MS) is shown to provide an efficient tech- nique for the investigation of polar composition of forensic tablets for male erectile dysfunction. ESI-MS fingerprinting of 41 commercial sildenafil samples (Viagra®, Cialis®, Lazar®, Libiden®, , Maxfil®, , Plenovit®, Potent 75®, Rigix®, V-50®, Vimax®, Pramil 75® and Pramil®) and 56 counterfeit samples (Viagra and Cialis) were obtained. The spectra for the authentic Viagra® tablets showed abundant ions exclusively corresponding to the sildenafil (SLD) molecule: [SLD + H]+ of m/z 475; [SLD + Na]+ of m/z 497; and [2SLD + H]+ of m/z 949. The spectra for com-mercial sildenafil samples also showed predominat SLD ions. Tablets of authentic Cialis® showed mainly ions of m/z 343, 365 and 707 from the lactose molecule (the excipient); as well as a minor ion of m/z 390 corresponding to the active ingredient tadalafil (TAD) in its protonated form [TAD + H]+. For counterfeit Cialis samples, how-ever, normally TAD ions of much high abundances was observed, together with ions corresponding to sildenafil analogues such as those of m/z 489 (homosildenafil) and 505 (hydroxyhomosildenafil). Principal component analysis was applied to ESI-MS fingerprint data, placing samples according to their contents of active ingredients hence authentic and counterfeit samples are easily recognized.

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R. Ortiz, K. Mariotti, W. Romão, M. Eberlin, R. Limberger and P. Mayorga, "Chemical Fingerprinting of Counterfeits of Viagra and Cialis Tablets and Analogues via Electrospray Ionization Mass Spectrometry," American Journal of Analytical Chemistry, Vol. 2 No. 8, 2011, pp. 919-928. doi: 10.4236/ajac.2011.28106.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] J. G. Hardman, L. E. Limbird and A. G. Gilman, “The Pharmacological Basis of Therapeutics,” 12th Edition, McGraw-Hill, New York, 2010.
[2] I. Wawer, M. Pisklak and Z. Chilmonczyk, “1H, 13C, 15N NMR Analysis of Sildenafil Base and Citrate (Viagra) in Solution, Solid State and Pharmaceutical Dosage Forms,” Journal of Pharmaceutical Biomedical Analysis, Vol. 38, No. 5, 2005, pp. 865-870. doi:10.1016/j.jpba.2005.01.046
[3] M. J. Vredenbregt, L. Blok-Tip, R. Hoogerbrugge, D. M. Barends and D. de Kaste, “Screening Suspected Counter- feit Viagra and Imitations of Viagra with Near-Infrared Spectroscopy,” Journal of Pharmaceutical Biomedical Analysis, Vol. 40, No. 4, 2006, pp. 840-849. doi:10.1016/j.jpba.2005.07.048
[4] J. Maurin, F. Plucinski, A. Mazurek and Z. Fijalek, “The Usefulness of Simple X-Ray Powder Diffraction Analysis for Counterfeit Control―The Viagra Example,” Journal of Pharmaceutical Biomedical Analysis, Vol. 43, No. 4, 2007, pp. 1514-1518. doi:10.1016/j.jpba.2006.10.033
[5] M. de Veij, A. Deneckere, P. Vandenabeele, D. de Kaste and L. Moens, “Detection of Counterfeit Viagra R with Raman Spectroscopy,” Journal of Pharmaceutical Bio- medical Analysis, Vol. 46, No. 2, 2008, pp. 303-309. doi:10.1016/j.jpba.2007.10.021
[6] R. S. Ortiz, M. V. Antunes and R. Linden, “Determina??o de Citrato de Sildenafila e de Tadalafila por Cro- matografia líquida de Ultraeficiência com Detec??o por Arranjo de Diodos (CLUE-DAD),” Química Nova, Vol. 33, No. 2, 2010, pp. 389-393. doi:10.1590/S0100-40422010000200028
[7] D. Zhong, J. Xing, S. Zhang and L. Sun, “Study of the Electrospray Ionization Tandem Mass Spectrometry of Sildenafil Derivatives,” Rapid Communication Mass Spectrometry, Vol. 16, No. 19, 2002, pp. 1836-1843. doi:10.1002/rcm.794
[8] S. R. Gratza, M. Zeller, D. W. Mincey and C. L. Flurer, “Structural Characterization of Sulfoaildenafil, an Analog of Sildenafil,” Journal of Pharmaceutical Biomedical Analysis, Vol. 50, No. 2, 2009, pp. 228-231. doi:10.1016/j.jpba.2009.04.003
[9] P. P. de Souza, L. C. A. de Oliveira, R. R. Catharino, M. N. Eberlin, D. V. Augusti, H. G. L. Siebald and R. Au- gusti, “Brazilian Cacha?a: ‘Single Shot’ Typification of Fresh Alembic and Industrial Samples via Electrospray Ionization Mass Spectrometry Fingerprinting,” Food Chemistry, Vol. 115, No. 3, 2009, pp. 1064-1068. doi:10.1016/j.foodchem.2008.12.026
[10] A. P. B. Gollücke, R. R. Catharino, J. C. de Souza, M. N. Eberlin and D. Q. Tavares, “Evolution of Major Phenolic Components and Radical Scavenging Activity of Grape Juices through Concentration Process and Storage,” Food Chemistry, Vol. 112, No. 4, 2009, pp. 868-873. doi:10.1016/j.foodchem.2008.06.060
[11] R. R. Catharino, H. M. S. Milagre, S. A. Saraiva, C. M. Garcia, U. Schuchardt and M. N. Eberlin, “Biodiesel Typification and Quality Control by Direct Infusion Electrospray Ionization Mass Spectrometry Fingerprint- ing,” Energy Fuels, Vol. 21, 2007, pp. 3698-3701. doi:10.1021/ef7003078
[12] A. C. L. Amorim, A. M. C. Hovell, A. C. Pinto, M. N. Eberlin, N. P. Arruda, E. J. Pereira, H. R. Bizzo, R. R. Catharino, Z. B. M. Filho and C. M. Rezende, “Green and Roasted Arabica Coffees Differentiated by Ripeness, Process and Cup Quality via Electrospray Ionization Mass Spectrometry Fingerprinting,” Journal of Brazilian Chemistry Society, Vol. 20, No. 2, 2009, pp. 313-321. doi:10.1590/S0103-50532009000200017
[13] L. A. Marques, R. R. Catharino, R. E. Bruns and M. N. Eberlin, “Electrospray Ionization Mass Spectrometry Fin- gerprinting of Perfumes: Rapid Classification and Coun- terfeit Detection,” Rapid Communication Mass Spectrometry, Vol. 20, No. 24, 2006, pp. 3654-3658. doi:10.1002/rcm.2779
[14] R. R. Catharino, R. Haddad, L. G. Cabrini, I. B. S. Cunha, A. C. H. F. Sawaya and M. N. Eberlin, “Characterization of Vegetable Oils by Electrospray Ionization Mass Spec- trometry Fingerprinting: Classification, Quality, Adul- teration, and Aging,” Analytical Chemistry, Vol. 77, No. 22, 2005, pp. 7429-7433. doi:10.1021/ac0512507
[15] A. C. H. F. Sawaya, D. M. Tomazela, I. B. S. Cunha, V. S. Bankova, M. C. Marcucci, A. R. Custodio and M. N. Eberlin, “Electrospray Ionization Mass Spectrometry Fin- gerprinting of Propolis,” Analyst, Vol. 129, No. 8, 2004, pp. 739-744. doi:10.1039/b403873h
[16] W. Rom?o, P. M. Lalli, M. F. Franco, G. Sanvido, N. V. Schwab, R. Lanaro, J. L. Costa, B. D. Sabino, M. I. M. S. Bueno, G. F. de Sa, R. J. Daroda, V. de Souza and M. N. Eberlin, “Chemical Profile of Meta-Chlorophenylpipera- Zine (m-CPP) in Ecstasy Tablets by Easy Ambient Sonic- spray Ionization, X-Ray Fluorescence, Ion Mobility Mass Spectrometry and NMR,” Analytical and Bioanalytical Chemistry, Vol. 400, No. 9, 2011, pp. 3053-3064. doi:10.1007/s00216-011-4883-9
[17] A. C. H. F. Sawaya, P. V. Abdelnur, M. N. Eberlin, S. Kumazawa, M. R. Ahn, K. S. Bang, N. Nagaraja, V. S. Bankova and H. Afrouzan, “Fingerprinting of Propolis by Easy Ambient Sonic-Spray Ionization Mass Spectrome- try,” Talanta, Vol. 81, No. 1-2, 2010, pp. 100-108. doi:10.1016/j.talanta.2009.11.043
[18] A. S. Araujo, L. L. da Rocha, D. M. Tomazela, A. C. H. F. Sawaya, R. R. Almeida, R. R. Catharino and M. N. Eber- lin, “Electrospray Ionization Mass Spectrometry Finger- printing of Beer,” Analyst, Vol. 130, No. 6, 2005, pp. 884-889. doi:10.1039/b415252b
[19] P. Zou, S. S. Oh, P. Hou, M. Low and H. Koh, “Simulta- neous Determination of Synthetic Phosphodiesterase-5 Inhibitors Found in a Dietary Supplement and Pre-Mixed Bulk Powders for Dietary Supplements Using High-Per- formance Liquid Chromatography with Diode Array De- tection and Liquid Chromatography-Electrospray Ioniza- tion Tandem Mass Spectrometry,” Journal of Chroma- tography A, Vol. 1104, No. 1-2, 2006, pp. 113-122. doi:10.1016/j.chroma.2005.11.103
[20] L. Blok-Tip, B. Zomer, F. Bakker, K. D. Hartog, M. Hamzink, J. Ten Hove, M. Vredenbregt and D. de Kaste, “Structure Elucidation of Sildenafil Analogues in Herbal Products,” Food Additive and Contamination, Vol. 21, No. 8, 2004, pp. 737-748. doi:10.1080/02652030412331272467
[21] S. Ahn, J. Y. Hong, M. K. Hong, Y. P. Jang, M. S. Oh, J. H. Jung and J. Hong, “Structural Determination of Silde- nafil and Its Analogues in Dietary Supplements by Fastatom Bombardment Collision-Induced Dissociation Tandem Mass Spectrometry,” Rapid Communication Mass Spectrometry, Vol. 23, No. 19, 2009, pp. 3158-3166. doi:10.1002/rcm.4238
[22] L Nyadong, G. A. Harris, S. Balayssac, A. S. Galhena, M. Malet-Martino, R. Martino, R. M. Parry, M. D. Wang, F. M. Fernández and V. Gilard, “Combining Two-Dimen- sional Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy, Imaging Desorption Electrospray Ioniza- tion Mass Spectrometry, and Direct Analysis in Real- Time Mass Spectrometry for the Integral Investigation of Counterfeit Pharmaceuticals,” Analytical Chemistry, Vol. 81, No. 12, 2009, pp. 4803-4812. doi:10.1021/ac900384j
[23] S. Singh, B. Prasad, A. Savaliya, R. Shah, V. Gohil and A. Kaur, “Strategies for Characterizing Sildenafil, Vardenafil, Tadalafil and Their Analogues in Herbal Dietary Supple- ments, and Detecting Counterfeit Products Containing These Drugs,” Trends Analytical Chemistry, Vol. 28, No. 1, 2009, pp. 13-28. doi:10.1016/j.trac.2008.09.004
[24] B. J. Venhuis, D. M. Barends, M. E. Zwaagstra and D. de Kaste, “Recent Developments in Counterfeits and Imita- tions of Viagra, Cialis and Levitra: A 2005-2006 Up- date,” National Institute for Public Health and the Envi- ronment (RIVM), Bilthoven, 2007.

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