Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic
C A Waffo Tchounga, P Y Sacre, P Ciza, R Ngono, E Ziemons, Ph H Hubert, R D Marini
Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2020.113761
The proliferation of falsified medicines can cause serious public health issues, particularly in the context of a global pandemic such as the actual COVID-19 pandemic. Our study involved eight chloroquine phosphate medicines seized in Cameroon, Democratic Republic of Congo and Niger during March and May 2020. These suspect samples were first analyzed in a screening phase using field tools such as handheld Raman spectroscopy (TruScan) and then in a confirmation phase using laboratory tools such as hyperspectral Raman imaging and High Performance Liquid Chromatography (HPLC). The results confirmed the falsified nature of the samples, highlighting the presence of metronidazole at low dose in four samples (16.6, 15.2, 15.2 and 14.5 mg/tab), too low levels of chloroquine in two samples (2.4 and 20.2 mg/tab), and substitution of chloroquine phosphate by paracetamol in one sample (255.7 mg/tab). The results also confirmed that four samples had been adulterated with paracetamol in trace amounts and two of them presented traces of chloramphenicol.
In the frame of the COVID-19 pandemic, the need for specific products (allegedly treating the disease) may increase rapidly at a global scale. This constitute an opportunity for criminal groups and unscrupulous sellers to sell substandard and falsified medicines. In this context, the application of rapid, easy-to-use techniques such as Raman spectroscopy should make it possible to combat efficiently the resurgence of poor-quality medicines. However, handheld devices are not sensitive enough to detect trace level contaminants or low-dosed active ingredients. Therefore, hyperspectral imaging may help in this context providing also a "signature" of the product composition possibly allowing the grouping of falsification cases.
CRediT authorship contribution statement
Declaration of Competing Interest The authors report no declarations of interest.
Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.jpba.2020. 113761.
References
Basco, Molecular epidemiology of malaria in Cameroon. xix. quality of antimalarial drugs used for self-medication, Am. J. Trop. Med. Hyg,
doi:10.1179/1364859411Y.0000000030Brunneton, La Qualité Des Médicaments Sur Le Marché Pharmaceutique Africain. Etude Analytique Dans Trois Pays: Cameroun, Madagascar, Tchad,
doi:10.4269/ajtmh.2004.70.245Ciza, Sacré, Waffo, Coïc, Avohou et al., Comparing the qualitative performances of handheld NIR and Raman spectrophotometers for the detection of falsified pharmaceutical products, Talanta,
doi:10.1016/j.talanta.2019.02.032Coic, Sacré, Dispas, Sakira, Fillet et al., Comparison of hyperspectral imaging techniques for the elucidation of falsified medicines composition, Talanta,
doi:10.1016/j.jpba.2012.09.016Coïc, Sacré, Avohou, Deidda, De Bleye et al., Recent developments of Raman spectroscopy for the qualitative analysis of falsified and substandard medicines, Eur. Pharm. Rev,
doi:10.1002/dta.1843Deidda, Sacré, Clavaud, Coïc, Avohou et al., Vibrational spectroscopy in analysis of pharmaceuticals: critical review of innovative portable and handheld NIR and Raman spectrophotometers, TrAC Trends Anal. Chem,
doi:10.1016/j.trac.2019.02.035Erku, Belachew, Abrha, Sinnollareddy, Thomas et al., When fear and misinformation go viral: pharmacists' role in deterring medication misinformation during the "infodemic" surrounding COVID-19, Res. Soc. Adm. Pharm,
doi:10.1186/s12916-020-01661-3Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int. J. Antimicrob. Agents,
doi:10.1016/j.ijantimicag.2020.105923Gnegel, Hauk, Neci, Mutombo, Nyaah et al., Identification of falsified chloroquine tablets in Africa at the time of the COVID-19 pandemic, Am. J. Trop. Med. Hyg,
doi:10.4269/ajtmh.20-0363Guerin, Singh-Phulgenda, Strub-Wourgaft, The consequence of COVID-19 on the global supply of medical products: why Indian generics matter for the world, F1000Research,
doi:10.1016/S2214-109X(20)30136-4Hajjou, Qin, Bradby, Bempong, Lukulay, Assessment of the performance of a handheld Raman device for potential use as a screening tool in evaluating medicines quality, J. Pharm. Biomed. Anal,
doi:10.1080/14787210.2016.1187560Newton, Bond, Adeyeye, Antignac, Ashenef et al., COVID-19 and risks to the supply and quality of tests, drugs, and vaccines, Lancet Glob. Health,
doi:10.1016/S2214-109X(20)30136-4Rebiere, Ghyselinck, Lempereur, Brenier, Investigation of the composition of anabolic tablets using near infrared spectroscopy and Raman chemical imaging, Drug Test. Anal,
doi:10.1016/j.jpba.2013.01.009Rodionova, Balyklova, Titova, Pomerantsev, Application of NIR spectroscopy and chemometrics for revealing of the 'high quality fakes' among the medicines, Forensic Chem,
doi:10.1016/j.jpba.2007.03.023Roggo, Chalus, Maurer, Lema-Martinez, Edmond et al., A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies, J. Pharm. Biomed. Anal,
doi:10.1016/s1473-3099(06)70581-3Sawadogo, Al-Kamarany, Al-Mekhlafi, Elkarbane, Al-Adhroey et al., Quality of chloroquine tablets available in Africa, Ann. Trop. Med. Parasitol,
doi:10.1016/S0140-6736(05)62397-5Schneider, Tu, Africa and counterfeit pharmaceuticals in the times of COVID-19, J. Intellect. Prop. Law Pract,
doi:10.1093/jiplp/jpaa073Who, A Study on the Public Health and Socioeconomic Impact of Substandard and Falsified Medical Products,
doi:10.1787/a7c7e054-en{ 'indexed': {'date-parts': [[2024, 3, 19]], 'date-time': '2024-03-19T19:32:05Z', 'timestamp': 1710876725935},
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'DOI': '10.1080/08998280.2020.1731272',
'article-title': '2019 novel coronavirus: an emerging global threat',
'volume': '33',
'author': 'Columbus',
'year': '2020',
'journal-title': 'Baylor Univ. Med. Cent. Proc.'},
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'DOI': '10.1111/1751-7915.13557',
'article-title': 'The novel coronavirus – a snapshot of current knowledge',
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'year': '2020',
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'DOI': '10.1093/trstmh/traa025',
'article-title': 'COVID-19: a fast evolving pandemic',
'volume': '114',
'author': 'Whitworth',
'year': '2020',
'journal-title': 'Trans. R. Soc. Trop. Med. Hyg.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0020',
'series-title': 'WHO COVID-19 Dashboard',
'year': '2020'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0025',
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'DOI': '10.1016/S2214-109X(20)30136-4',
'article-title': 'COVID-19 and risks to the supply and quality of tests, drugs, and '
'vaccines',
'volume': '8',
'author': 'Newton',
'year': '2020',
'journal-title': 'Lancet Glob. Health'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0030',
'doi-asserted-by': 'crossref',
'first-page': '225',
'DOI': '10.12688/f1000research.23057.1',
'article-title': 'The consequence of COVID-19 on the global supply of medical products: '
'why Indian generics matter for the world?',
'volume': '9',
'author': 'Guerin',
'year': '2020',
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'doi-asserted-by': 'crossref',
'first-page': '193',
'DOI': '10.1186/s12916-020-01661-3',
'article-title': 'Why the COVID-19 pandemic should be a call for action to advance '
'equitable access to medicines',
'volume': '18',
'author': 'Kohler',
'year': '2020',
'journal-title': 'BMC Med.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0040',
'article-title': 'When fear and misinformation go viral: pharmacists’ role in deterring '
'medication misinformation during the “infodemic” surrounding COVID-19',
'author': 'Erku',
'year': '2020',
'journal-title': 'Res. Soc. Adm. Pharm.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0045',
'series-title': 'Trade in Counterfeit Pharmaceutical Products, Illicit Trade',
'first-page': '94',
'author': 'OECD/EUIPO',
'year': '2020'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0050',
'series-title': 'A Study on the Public Health and Socioeconomic Impact of Substandard and '
'Falsified Medical Products',
'author': 'WHO',
'year': '2017'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0055',
'doi-asserted-by': 'crossref',
'first-page': '417',
'DOI': '10.1093/jiplp/jpaa073',
'article-title': 'Africa and counterfeit pharmaceuticals in the times of COVID-19',
'volume': '15',
'author': 'Schneider',
'year': '2020',
'journal-title': 'J. Intellect. Prop. Law Pract.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0060',
'series-title': 'WHO Global Surveillance and Monitoring System for Substandard and '
'Falsified Medical Products',
'author': 'WHO',
'year': '2017'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0065',
'volume': '31',
'author': 'European Medicines Agency',
'year': '2020'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0070',
'doi-asserted-by': 'crossref',
'first-page': '105923',
'DOI': '10.1016/j.ijantimicag.2020.105923',
'article-title': 'Chloroquine for the 2019 novel coronavirus SARS-CoV-2',
'volume': '55',
'author': 'Colson',
'year': '2020',
'journal-title': 'Int. J. Antimicrob. Agents'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0075',
'doi-asserted-by': 'crossref',
'first-page': '105949',
'DOI': '10.1016/j.ijantimicag.2020.105949',
'article-title': 'Hydroxychloroquine and azithromycin as a treatment of COVID-19: results '
'of an open-label non-randomized clinical trial',
'volume': '56',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Int. J. Antimicrob. Agents'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0080',
'series-title': 'Medical Product Alert N°4/2020',
'author': 'World Health Organization (WHO)',
'year': '2020'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0085',
'series-title': 'UPDATE (of 9 June 2020) to Medical Product Alert n°4/2020',
'author': 'World Health Organization (WHO)',
'year': '2020'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0090',
'doi-asserted-by': 'crossref',
'first-page': '73',
'DOI': '10.4269/ajtmh.20-0363',
'article-title': 'Identification of falsified chloroquine tablets in Africa at the time '
'of the COVID-19 pandemic',
'volume': '103',
'author': 'Gnegel',
'year': '2020',
'journal-title': 'Am. J. Trop. Med. Hyg.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0095',
'doi-asserted-by': 'crossref',
'first-page': '1395',
'DOI': '10.1016/S0140-6736(89)92002-3',
'article-title': 'Chloroquine-resistant plasmodium VIVAX',
'volume': '334',
'author': 'Whitby',
'year': '1989',
'journal-title': 'Lancet'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0100',
'doi-asserted-by': 'crossref',
'first-page': '4075',
'DOI': '10.1128/AAC.48.11.4075-4083.2004',
'article-title': 'Chloroquine resistance in plasmodium vivax',
'volume': '48',
'author': 'Baird',
'year': '2004',
'journal-title': 'Antimicrob. Agents Chemother.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0105',
'doi-asserted-by': 'crossref',
'first-page': '224',
'DOI': '10.1016/S0140-6736(05)62397-5',
'article-title': 'False chloroquine resistance in Africa',
'volume': '350',
'author': 'Basco',
'year': '1997',
'journal-title': 'Lancet'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0110',
'doi-asserted-by': 'crossref',
'first-page': '447',
'DOI': '10.1179/1364859411Y.0000000030',
'article-title': 'Quality of chloroquine tablets available in Africa',
'volume': '105',
'author': 'Sawadogo',
'year': '2011',
'journal-title': 'Ann. Trop. Med. Parasitol.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0115',
'doi-asserted-by': 'crossref',
'first-page': '245',
'DOI': '10.4269/ajtmh.2004.70.245',
'article-title': 'Molecular epidemiology of malaria in Cameroon. xix. quality of '
'antimalarial drugs used for self-medication',
'volume': '70',
'author': 'BASCO',
'year': '2004',
'journal-title': 'Am. J. Trop. Med. Hyg.'},
{'key': '10.1016/j.jpba.2020.113761_bib0120', 'volume': '3', 'year': '1995'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0125',
'doi-asserted-by': 'crossref',
'first-page': '602',
'DOI': '10.1016/S1473-3099(06)70581-3',
'article-title': 'Counterfeit anti-infective drugs',
'volume': '6',
'author': 'Newton',
'year': '2006',
'journal-title': 'Lancet Infect. Dis.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0130',
'doi-asserted-by': 'crossref',
'first-page': '683',
'DOI': '10.1016/j.jpba.2007.03.023',
'article-title': 'A review of near infrared spectroscopy and chemometrics in '
'pharmaceutical technologies',
'volume': '44',
'author': 'Roggo',
'year': '2007',
'journal-title': 'J. Pharm. Biomed. Anal.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0135',
'doi-asserted-by': 'crossref',
'first-page': '82',
'DOI': '10.1016/j.forc.2018.02.004',
'article-title': 'Application of NIR spectroscopy and chemometrics for revealing of the '
'‘high quality fakes’ among the medicines',
'volume': '8',
'author': 'Rodionova',
'year': '2018',
'journal-title': 'Forensic Chem.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0140',
'doi-asserted-by': 'crossref',
'first-page': '167',
'DOI': '10.1016/j.jpba.2013.01.009',
'article-title': 'Understanding and fighting the medicine counterfeit market',
'volume': '87',
'author': 'Dégardin',
'year': '2014',
'journal-title': 'J. Pharm. Biomed. Anal.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0145',
'article-title': 'Investigation of the composition of anabolic tablets using near '
'infrared spectroscopy and Raman chemical imaging',
'volume': '8',
'author': 'Rebiere',
'year': '2015',
'journal-title': 'Drug Test. Anal.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0150',
'first-page': '46',
'article-title': 'Recent developments of Raman spectroscopy for the qualitative analysis '
'of falsified and substandard medicines',
'volume': '23',
'author': 'Coïc',
'year': '2018',
'journal-title': 'Eur. Pharm. Rev.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0155',
'doi-asserted-by': 'crossref',
'first-page': '251',
'DOI': '10.1016/j.trac.2019.02.035',
'article-title': 'Vibrational spectroscopy in analysis of pharmaceuticals: critical '
'review of innovative portable and handheld NIR and Raman '
'spectrophotometers',
'volume': '114',
'author': 'Deidda',
'year': '2019',
'journal-title': 'TrAC Trends Anal. Chem.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0160',
'doi-asserted-by': 'crossref',
'first-page': '531',
'DOI': '10.1080/14787210.2016.1187560',
'article-title': 'A link between poor quality antimalarials and malaria drug resistance?',
'volume': '14',
'author': 'Newton',
'year': '2016',
'journal-title': 'Expert Rev. Anti-Infect. Ther.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0165',
'doi-asserted-by': 'crossref',
'first-page': '47',
'DOI': '10.1016/j.jpba.2012.09.016',
'article-title': 'Assessment of the performance of a handheld Raman device for potential '
'use as a screening tool in evaluating medicines quality',
'volume': '74',
'author': 'Hajjou',
'year': '2013',
'journal-title': 'J. Pharm. Biomed. Anal.'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0170',
'doi-asserted-by': 'crossref',
'first-page': '457',
'DOI': '10.1016/j.talanta.2019.02.032',
'article-title': 'Comparison of hyperspectral imaging techniques for the elucidation of '
'falsified medicines composition',
'volume': '198',
'author': 'Coic',
'year': '2019',
'journal-title': 'Talanta'},
{ 'key': '10.1016/j.jpba.2020.113761_bib0175',
'doi-asserted-by': 'crossref',
'first-page': '469',
'DOI': '10.1016/j.talanta.2019.04.049',
'article-title': 'Comparing the qualitative performances of handheld NIR and Raman '
'spectrophotometers for the detection of falsified pharmaceutical '
'products',
'volume': '202',
'author': 'Ciza',
'year': '2019',
'journal-title': 'Talanta'}],
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