Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic
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.
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.0000000030
Brunneton, La Qualité Des Médicaments Sur Le Marché Pharmaceutique Africain. Etude Analytique Dans Trois Pays: Cameroun, Madagascar, Tchad, doi:10.4269/ajtmh.2004.70.245
Ciza, 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.2019.02.032
Coic, Sacré, Dispas, Sakira, Fillet et al., Comparison of hyperspectral imaging techniques for the elucidation of falsified medicines composition, Talanta, doi:10.1016/j.jpba.2012.09.016
Coïc, 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.1843
Deidda, 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.2019.02.035
Erku, 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/s12916-020-01661-3
Gautret, 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.2020.105923
Gnegel, 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.20-0363
Guerin, 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)30136-4
Hajjou, 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:10.1080/14787210.2016.1187560
Newton, 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)30136-4
Rebiere, 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.2013.01.009
Rodionova, 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.2007.03.023
Roggo, 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)70581-3
Sawadogo, 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)62397-5
Schneider, Tu, Africa and counterfeit pharmaceuticals in the times of COVID-19, J. Intellect. Prop. Law Pract, doi:10.1093/jiplp/jpaa073
Who, A Study on the Public Health and Socioeconomic Impact of Substandard and Falsified Medical Products, doi:10.1787/a7c7e054-en