Browse > Article
http://dx.doi.org/10.5806/AST.2015.28.4.278

Identification and evaluation of fragmentation pathways of PDE-5 inhibitor analogues using LC-QTOF-MS  

Do, Jung-Ah (Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Noh, Eunyoung (Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Yoon, Soon-Byung (Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Park, Hyoung-Joon (Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Cho, Sooyeul (Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Park, Sung-Kwan (Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Yoon, Chang-Yong (Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Publication Information
Analytical Science and Technology / v.28, no.4, 2015 , pp. 278-287 More about this Journal
Abstract
Phosphodiesterase type 5 inhibitors (PDE-5 inhibitors) are used in the treatment of erectile dysfunction. In recent years, a number of reports have been conducted on dietary supplements contaminated with PDE-5 analogues. In this study, 58 analogues of PDE-5 inhibitors were sorted into five groups: tadalafil, sildenafil, hongdenafil, vardenafil, and other analogues. These analogues were then evaluated using a liquid chromatography-quadrupole-time of flight mass spectrometry (LC-QTOF-MS) electrospray ionization mass method. Each compound has a unique fragmentation ion, which can be easily analyzed qualitatively. The fragmentation pathways of the analogues were elucidated based on the QTOF-MS and MS/MS data. Common ions were confirmed for each group by analyzing the structural characteristics and fragmentation pathways. Specifically, common ions were observed at m/z 169.08 and 135.04 (tadalafil analogues), m/z 311.15 and 283.12 (sildenafil analogues and hongdenafil analogues), and m/z 312.16 and 151.09 (vardenafil analogues). The advantage of this method is that the structure of unknown components can be determined by interpreting the product ions. Hence, the developed method can be used for the identification of unknown compounds. Fragmentation pathways may also aid in the detection and identification of PDE-5 inhibitor analogues.
Keywords
PDE-5; LC-QTOF-MS; fragmentation pathway; identification; unknown compounds;
Citations & Related Records
연도 인용수 순위
  • Reference
1 C. N. Man, N. M. Noor and R. Lajis, J. Chromatogr., 1218(39), 7055-7060 (2011).   DOI
2 P. Nikolaou, I. Papoutsis, S. Athanaselis, G. Alevisopoulos, A. Khraiwesh, C. Pistos and C. Spiliopoulou, J. Pharm. Biomed. Anal., 56(3), 577-581 (2011).   DOI
3 R. Patterson, P. Mabe, E. N. Mitchell and W. Cory, Forensic Sci. Int., 222(1-3), 83-88 (2012).   DOI
4 C. S. Ng, T. Y. Law, Y. K. Cheung, P. C. Ng and K. K. Choi, Anal. Methods., 2, 890-896 (2010).   DOI
5 Y. Ren, C. S. Wu and J. L. Zhang, J. Sep. Sci., 35(21), 2847-2857 (2012).   DOI
6 M. E. Hadwiger, M. L. Trehy, W. Ye, T. Moore, J. Allgire and B. Westenberger, J. Chromatogr. A., 1217(48), 7547-7555 (2010).   DOI
7 C. L. Cheng, G. J. Kang and C. H. Chou, J. Chromatogr., 1154(1-2), 222-229 (2007).   DOI
8 M. Park and S. Ahn, J. Forensic Sci., 57(6), 1637-1640 (2012).   DOI
9 Y. Cai, T. G. Cai, Y. Shi, X. L. Cheng, L. Y. Ma, S. C. Ma, R. C. Lin and W. Feng, J. Liq. Chromatogr. Rel. Technol., 33, 1287-1306 (2010).   DOI
10 A. Lanzarotta, J. B. Crowe, M. Witkowski and B. M. Gamble, J. Pharm. Biomed. Anal., 67-68, 22-27 (2012).   DOI
11 F. W. McLafferty. Interpretation of Mass Spectra, third edition. University Science Books, p 51-215, Mill Valley, California, 1980.
12 A. W. Shindel. Update on phosphodiesterase type 5 inhibitor therapy part 2: updates on optimal utilization for sexual concerns and rare toxicities in this class. J. Sex. Med., 6, 2352-2364 (2009).   DOI
13 C. G. Stief, S. Uckert, A. J. Becker, M. C. Truss and U. Jonas, J. Urol., 159(4), 1390-1393 (1998).   DOI
14 B. J. Venhuis and D. Kaste, J. Pharm. Biomed. Anal., 69, 196-208 (2012).   DOI
15 M. Y. Low, Y. Zeng, L. Li, X. W. Ge, R. Lee and B. C. Bloodworth, H. L. Koh, Drug Saf., 32(12), 1141-1146 (2009).   DOI
16 Illicit erectile dysfunction products in the Netherlands http://www.rivm.nl/Documenten_en_publicaties/Wetenschappelijk/Rapporten/2011/september/Illicit_erectile_dysfunction_products_in_the_Netherlands_A_decade_of_trends_and_a_2007_2010_product_update/, Assessed 8 Sept 2011.
17 M. Sugita and M. Miyakawa, Health Preventive Med., 15(4), 244-251 (2010).   DOI
18 S. Singh, B. Prasad, A. A. Savaliya, R. P. Shah and V. M. Gohil, A. Kaur, Trends Anal. Chem., 28(1), 13-28 (2009).   DOI
19 J. B. Guo, Y. Xu, Z. B. Huang, Q. H. He, S. W. Liu, Anal. Chim., 658(2), 197-203 (2010).   DOI
20 S. M. Khalil, Microchim., 158, 233-238 (2007).   DOI
21 C. M. Gryniewicz, J. C. Reepmeyer, J. F. Kauffman and L. F. Buhse, J. Pharm. Biomed. Anal., 49(3), 601-606 (2009).   DOI
22 D. J. Mans, R. J. Callahan, J. D. Dunn and C. M. Gryniewicz-Ruzicka, J. Pharm. Biomed. Anal., 75(5), 153-157 (2013).   DOI
23 D. Z. Mao, X. X. Weng and Y. J. Yang, J. Raman Spectrosc., 43(12), 1985-1990 (2012).   DOI
24 B. J. Venhuis, G. Zomer, M. Hamzink, H. D. Meiring, Y. Aubin and D. de Kaste, J. Pharm. Biomed. Anal., 54(4), 735-741 (2011).   DOI
25 M. H. Shin, M. K. Hong, W. S. Kim, Y. J. Lee and Y. C. Jeoung, Food Addit. Contam., 20(9), 793-798 (2003).   DOI
26 L. Blok-Tip, B. Zomer, F. Bakker, K. D. Hartog, M. Hamzink, J. Ten Hove, M. Vredenbregt, D. de Kaste, Food Addit. Contam., 21(8), 737-748 (2004).   DOI
27 Q. Liang, J. Qu, G. Luo and Y. Wang, J. Pharm. Biomed. Anal., 40(2), 305-311 (2006).   DOI
28 S. R. Gratz, C. L. Flurer and K. A. Wolnik, J. Pharm. Biomed. Anal., 36(3), 525-533 (2004).   DOI
29 R. Yuan and Y. Lin, Pharmacol. Ther., 86(2), 191-198 (2000).   DOI
30 FDA approves Stendra for erectile dysfunction, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm302140.htm/, Assessed 13 Jan 2001.
31 O. Shaeer. The Global Online Sexuality Survey (GOSS): The United States of America in 2011 Chapter II: phosphodiesterase inhibitors utilization among English speakers. J. Sex. Med., 10(2), 532-540 (2012).   DOI
32 P. Y. Sacre, E. Deconinck, P. Chiap, J. Crommen, F. Mansion, E. Rozet, P. Courselle and J. O. De Beer, J. Chromatogr., 1218(37), 6439-6447 (2011).   DOI
33 J. H. Lee, H. J. Kim, E. Noh, J. Y. Kim, S. H. Cho, J.-A Do, C.-Y. Yoon, S. Cho and W. S. Kim, J. Pharm. Biomed. Anal., 103, 80-84 (2015).   DOI