1921
Volume 98, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

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References

  1. World Health Organization, 2017. Substandard and Falsified (SF) Medical Products. Available at: http://www.who.int/medicines/regulation/ssffc/en/. Accessed June 22, 2017.
  2. Hall KA, Newton PN, Green MD, De Veij M, Vandenaabele P, Pizzanelli D, Mayfong M, Dondorp A, Fernández F, , 2006. Characterization of counterfeit artesunate antimalarial tablets from southeast Asia. Am J Trop Med Hyg 75: 804811. [Google Scholar]
  3. Security PG, . A Serious Threat to Patient Safety, Counterfeit Pharmaceuticals. Available at: http://www.pfizer.com/files/products/CounterfeitBrochure.pdf. Accessed May 13, 2016.
  4. de Peinder P, Vredenbregt MJ, Visser T, de Kaste D, , 2008. Detection of Lipitor® counterfeits: a comparison of NIR and Raman spectroscopy in combination with chemomertrics. J Pharm Biomed Anal 47: 688694. [Google Scholar]
  5. Lopes MB, Wolff J-C, , 2009. Investigation into classification/sourcing of suspect counterfeit Heptodin™ tablets by near infrared chemical imaging. Anal Chim Acta 633: 149155. [Google Scholar]
  6. Kovacs S, Hawes SE, Maley SN, Mosites E, Wong K, Stergachis A, , 2014. Technologies for detecting falsified and substandard drugs in low and middle-income countries. PLoS One 9: e90601. [Google Scholar]
  7. Dowell FE, Maghirang EB, Fernandez FM, Newton PN, Green MD, , 2008. Detecting counterfeit antimalarial tablets by near-infrared spectroscopy. J Pharm Biomed Anal 48: 10111014. [Google Scholar]
  8. Ranieri N, 2014. Evaluation of a new handheld instrument for the detection of counterfeit artesunate by visual fluorescence comparison. Am J Trop Med Hyg 91: 920924. [Google Scholar]
  9. Holzgrabe U, Malet-Martino M, , 2011. Analytical challenges in drug counterfeiting and falsification-The NMR approach. J Pharm Biomed Anal 55: 679687. [Google Scholar]
  10. Puchert T, Lochmann D, Menezes JC, Reich G, , 2010. Near-infrared chemical imaging (NIR-CI) for counterfeit drug identification—a four-stage concept with a novel approach of data processing (linear image signature). J Pharm Biomed Anal 51: 138145. [Google Scholar]
  11. Rodionova OYe, Pomerantsev AL, , 2010. NIR-based approach to counterfeit-drug detection. TrAC Trends Analyt Chem 29: 795803. [Google Scholar]
  12. Reviere H, Guinot P, Chauvey N, Brenier C, , 2017. Fighting falsified medicines: the analytical approach. J Pharm Biomed Anal 142: 286306. [Google Scholar]
  13. Pharmaceutical Security Institute, 2016. Incident-Regions of the World. Available at: http://www.psi-inc.org/geographicDistributions.cfm. Accessed June 19, 2016. [Google Scholar]
  14. Banerjee Y, , 2017. Counterfeit and substandard drugs in sub-Saharan Africa may pose a major hurdle to H3Africa’s initiative to study genetics of kidney disease progression. Kidney Int 91: 252253. [Google Scholar]
  15. Antignac M, 2017. Fighting fake medicines: first quality evaluation of cardiac drugs in Africa. Int J Cardiol 243: 523528. [Google Scholar]
  16. World Health Organization, 2016. SSFFC Medical Products. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/mediacentre/factsheets/fs275/en/. Accessed June 19, 2016.
  17. Khan MH, Okumura J, Sovannarith T, Nivanna N, Akazawa M, Kimura K, , 2010. Prevalence of counterfeit anthelminthic medicines: a cross-sectional survey in Cambodia. Trop Med Int Health 15: 639644. [Google Scholar]
  18. Khan MH, Okumura J, Sovannarith T, Nivanna N, Nagai H, Tara M, Yoshida N, Akazawa M, Tanimoto T, Kimura K, , 2011. Counterfeit medicines in Cambodia—possible causes. Pharm Res 28: 484489. [Google Scholar]
  19. Hoellein L, Holzgrabe U, , 2014. Development of simplified HPLC methods for the detection of counterfeit antimalarials in resource-restraint environments. J Pharm Biomed Anal 98: 434445. [Google Scholar]
  20. Grech J, Robertson J, Thomas J, Cooper G, Naunton M, Kelly T, , 2018. An empirical review of antimalarial quality field surveys: the importance of characterising outcomes. J Pharm Biomed Anal 147: 612623. [Google Scholar]
  21. Been F, Yves RKD, Esseiva P, Margot P, , 2011. Profiling of counterfeit medicines by vibrational spectroscopy. Forensic Sci Int 211: 83100. [Google Scholar]
  22. Dégardin K, Roggo Y, Margot P, , 2014. Understanding and fighting the medicine counterfeit market. J Pharm Biomed Anal 87: 167175. [Google Scholar]
  23. ICH Harmonised Tripartite Guideline Q6A , 1999. Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products. Available at: https://www.pmda.go.jp/files/000156754.pdf. Accessed June 22, 2017.
  24. Höllein L, Kaale E, Mwalwisi YH, Schulze MH, Holzgrabe U, , 2016. Routine quality control of medicines in developing countries: analytical challenges, regulatory infrastructures and the prevalence of counterfeit medicines in Tanzania. TrAC Trends Anal Chem 72: 6070. [Google Scholar]
  25. Custers D, Krakowska B, De Beer JO, Coureselle P, Daszykowski M, Apers S, Deconinck E, , 2016. Chromatographic impurity fingerprinting of genuine and counterfeit Cialis® as a means to compare the discriminating ability of PDA and MS detection. Talanta 146: 540548. [Google Scholar]
  26. Plonka M, Walorczyk S, Miszczyk M, , 2016. Chromatographic methods for the determination of active substances and characterization of their impurities in pesticide formulations. TrAC Trends in Analytical Chemistry 85: 6780. [Google Scholar]
  27. Custers D, Cauwenbergh T, Bothy JL, Courselle P, De Beer JO, Apers S, Deconinck E, , 2015. ATR-FTIR spectroscopy and chemometrics: an interesting tool to discriminate and characterize counterfeit. J Pharm Biomed Anal 112: 181189. [Google Scholar]
  28. Stewart MW, Narayanan R, Gupta V, Rosenfeld PJ, Martin DF, Chakravarthy U, , 2016. Counterfeit Avastin in India: punish the criminals, not the patients. Am J Ophthalmol 170: 228231. [Google Scholar]
  29. Conway J, Bero L, Ondari C, Wasan KM, , 2013. Review of the quality of pediatric medications in developing countries. J Pharm Sci 102: 14191433. [Google Scholar]
  30. Ministry of Health, Labour and Welfare, 2016. Candesartan cilexetil tablets. Drug Monograph of the Japanese Pharmacopea, 17th edition. Tokyo, Japan: Ministry of Health, Labour and Welfare, 663–665.
  31. Habyalimana V, Mbinze JK, Yemoa AL, Waffo C, Diallo T, Tshilombo NK, Ntokamunda JK, Lebrun P, Hubert P, Marini RD, , 2017. Application of design space optimization strategy to the development of LC methods for simultaneous analysis of 18 antiretroviral medicines and 4 major excipients used in various pharmaceutical formulations. J Pharm Biomed Anal 139: 821. [Google Scholar]
  32. Abdellah A, Noordin MI, Wan AWI, , 2015. Importance and globalization status of good manufacturing practice (GMP) requirements for pharmaceutical excipients. Saudi Pharm J 23: 913. [Google Scholar]
  33. García-Arieta A, , 2014. Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence. Eur J Pharm Sci 65: 8997. [Google Scholar]
  34. Kakio T, Yoshida N, Macha S, Moriguchi K, Hiroshima T, Ikeda Y, Tsuboi H, Kimura K, , 2017. Classification and visualization of physical and chemical properties of falsified medicines with handheld Raman spectroscopy and x-ray computed tomography. Am J Trop Med Hyg 97: 684689. [Google Scholar]
  35. Shinzawa H, Hashimoto K, Sato H, Kanematsu W, Noda I, , 2014. Multiple-perturbation two-dimensional (2D) correlation analysis for spectroscopic imaging data. J Mol Struct 1069: 176182. [Google Scholar]
  36. Sacre P-Y, De Bleye C, Chavez P-F, Netchacovitch L, Hubert Ph, Ziemons E, , 2014. Data processing of vibrational chemical imaging for pharmaceutical applications. J Pharm Biomed Anal 101: 123140. [Google Scholar]
  37. Watanabe A, Morita S, Kokot S, Matsubara M, Fukai K, Ozaki Y, , 2006. Drying process of microcrystalline cellulose studied by attenuated total reflection IR spectroscopy with two-dimensional correlation spectroscopy and principal component analysis. J Mol Struct 799: 102110. [Google Scholar]
  38. Franco D, 2017. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines. Spectrochim Acta A Mol Biomol Spectrosc 187: 1522. [Google Scholar]
  39. Hasegawa T, , 2007. Quantitative Analytical Techniques of Spectra, 2nd edition. Tokyo, Japan: Kodansya.
  40. Shimada T, Hasegawa T, , 2017. Determination of equilibrium structures of bromothymol blue revealed by using quantum chemistry with an aid of multivariate analysis of electronic absorption spectra. Spectrochim Acta A Mol Biomol Spectrosc 185: 104110. [Google Scholar]
  41. Shimaoka T, Hasegawa T, , 2016. Molecular structural analysis of hydrated ethylene glycol accounting for the antifreeze effect by using infrared attenuated total reflection spectroscopy. J Mol Liq 223: 621627. [Google Scholar]
  42. Hasegawa T, , 2001. Detection of minute chemical signals by principal component analysis. TrAC Trends Anal Chem 20: 5364. [Google Scholar]
  43. Hasegawa T, Nishijo J, Umemura J, , 2000. Separation of Raman spectra from fluorescence emission background by principal component analysis. Chem Phys Lett 317: 642646. [Google Scholar]
  44. Ministry of Health, Labour and Welfare, 2016. “1.Conent uniformity” in <6.02>. Drug Monograph of the Japanese Pharmacopea, 17th edition. Tokyo, Japan: Ministry of Health, Labour and Welfare, B-604–B-613.
  45. Lohumi S, Kim MS, Qin J, Cho B-K, , 2017. Raman imaging from microscopy to macroscopy: quality and safety control of biological materials. TrAC Trends Analyt Chem 93: 183198. [Google Scholar]
  46. Xie Y, Yang L, Sun X, Wu D, Chen Q, Zeng Y, Liu G, , 2016. An auto-adaptive background subtraction method for Raman spectra. Spectrochim Acta A Mol Biomol Spectrosc 161: 5863. [Google Scholar]
  47. Ritthiruangdej P, Ritthiron R, Shinzawa H, Ozaki Y, , 2011. Non-destructive and rapid analysis of chemical compositions in Thai steamed pork sausages by near-infrared spectroscopy. Food Chem 129: 684692. [Google Scholar]
  48. Næs T, Isaksson T, Fearn T, Davies T, , 2002. A User-Friendly Guide to Multivariate Calibration and Classification. Chichester, United Kingdom: NIR Publications.
  49. Phatak A, , 2004. Book review of a user-friendly guide to multivariate calibration and classification. Chemom Intell Lab Syst 71: 7981. [Google Scholar]
  50. Kakio T, Hiroshima T, Ikeda Y, , 2014. Development of quantitative analysis for Polymorph of drug substances in pharmaceutical oral dosage forms by XRPD and Raman spectroscopy. J Pharm Machinery Eng 23: 140146. [Google Scholar]
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  • Received : 11 Jul 2017
  • Accepted : 19 Jan 2018
  • Published online : 02 Apr 2018

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