PCA on pre-processed (2 nd derivative + MSC) spectra (1085 – 1601 nm) Identification of falsified antimalarial drugs using an innovative low cost portable near infrared spectrophotometer Analyzed samples Moussa Yabré 1, 2, * , Abdoul Karim Sakira 2 , Ludivine Ferey 1 , Pierre-Yves Sacré 3 , Roland D. Marini 3 , Karen Gaudin 1 , Issa T. Somé 2 1 ChemBioPharm - ARNA INSERM U1212 / UMR CNRS 5320, Université de Bordeaux, France 2 Laboratoire du développement du médicament, Université Joseph Ki-Zerbo, Burkina Faso 3 Laboratoire de Chimie Analytique, Département de Pharmacie, CIRM, Université de Liège, Belgique * [email protected] ; [email protected] Thanks INTRODUCTION The phenomenon of substandard and falsified drugs becomes a serious threat to public health in the worldwide, particularly in developing countries where drugs monitoring and quality control (QC) systems are not very efficient. The occurrence of fake medicines increases therapeutic failure, morbidity and mortality and the risk of treatment resistance. [1] Kovacs S, Hawes SE, Maley SN, Mosites E, Wong L, Stergachis A. Technologies for Detecting Falsified and Substandard Drugs in Low and Middle-Income Countries. PLoS ONE, 9(3):e90601, 2014. [2] Dégardin K, Guillemain A, Guerreiro NV, Roggo Y. Near infrared spectroscopy for counterfeit detection using a large database of pharmaceutical tablets. Journal of Pharmaceutical and Biomedical Analysis, 128:89-97, 2016. [3] Ciza PH, Sacre P-Y, Waffo C, Coïc L, Avohou H, Mbinze JK, Ngono R, Marini RD, Hubert Ph, Ziemons E. Comparing the qualitative performances of handheld NIR and Raman spectrophotometers for the detection of falsified pharmaceutical products. Talanta, 202:469-78, 2019. References Second and quantitative QC of all samples by HPLC or HPTLC to identify substandard drugs Evaluation of the handheld device ability to detect substandard drugs Collection of more samples to build DD-SIMCA models for each brand name Use of DD-SIMCA models built in routine analysis Perspectives NIR-S-G1 (spectral range: 900-1700 nm) Data Driven (DD)-SIMCA Classification API Brand name Dosage (mg) Sales channel Designation Test batches AL Dispersible S.Kant 20/120 Licite AL 20/120 dispersible S. Kant 1 AL Ipca 20/120 Licite AL Ipca 2 AL Macleods 20/120 Licite AL Macleods 5 AL S.Kant 80/480 Licite AL 80/480 S. Kant 3 AL Artefan 20/120 Licite Artefan 20/120 1 AL Artefan 40/240 Licite Artefan 40/240 1 AL Artefan 60/360 Licite Artefan 60/360 1 AL Artefan 80/480 Licite Artefan 80/480 1 AL Artefan Dispersible 20/120 Licite Artefan 20/120 dispersible 3 API Brand name Dosage (mg) Sales channel Designation Test batches AL Coartem 20/120 Illicite Coartem 20/120 illicite channel 2 AL Coartem 80/480 Licite Coartem 80/480 licite channel 1 AL Colart 20/120 Licite Colart 1 AL Combiart 80/480 Licite Combiart 80/480 licite channel 1 AL Combiart 20/120 Licite Combiart 20/120 licite channel 7 AL Combiart 20/120 Illicite Combiart 20/120 illicite channel 3 AL Falciart 80/480 Licite Falciart 1 AL Komefan 20/120 Licite Komefan 5 AL R-Lume 80/480 Licite R-Lume 1 API Brand name Dosage (mg) Sales channel Designation Test batches DP Duocotecxin 40/320 Licite Duocotecxin 6 DP Ridmal 40/320 Licite Ridmal 2 DP Malacur 40/320 Licite Malacur 2 SP Maloxine 500/25 Licite Maloxine licite channel 5 SP Maloxine 500/25 Illicite Maloxine illicite channel 3 SP Combimal 500/25 Licite Combimal 2 SP Laridox 500/25 Licite Laridox 2 SP Fansidar 500/25 Licite Fansidar 2 SP SP Strides Arcolab 500/25 Licite SP Strides Arcolab 1 SP AL DP Atypic samples Coartem and combiart samples bought in illicite sale channel are falsified without declared API One of Duocotecxin batch is falsified without declared API Maloxine samples from illicite sale channel are falsified without declared API PCA on all AL DP SP data PCA on all DP data PCA on all SP data PCA on all AL data AL pre-processed mean spectra Test of ability to identify a brand name Genuine samples • AL : Combiart • DP : Duocotecxin • SP : Maloxine Calibration set : at least 3 batches Validation set : at least 2 independant batches 20 spectra per batch In this study, we evaluated the potential of a low cost handheld NIR spectrophotometer (NIR-S-G1) in the identification of falsified drugs of different antimalarial tablets: The potential of spectroscopy techniques such as near infrared (NIR) and Raman associated to chemometric methods in the detection of substandard and falsified drugs are well known [1,2]. Also, these techniques have the advantages of being non- destructive, fast, requiring little or no sample preparation, as well as being environmental friendly. However, the high cost of instruments classically commercialized limits their use in developing countries. Recently, some innovative handheld and low cost NIR spectrophotometers (< 1000 €) have appeared on the market. Besides their low cost, these portable devices can offer promising performance comparable to bench-top instruments [3]. DP pre-processed mean spectra SP pre-processed mean spectra Samples were collected in Burkina Faso mainly in rural and border areas. artemether/lumefantrine (AL) dihydroartemisinin/piperaquine (DP) sulfadoxine/pyrimethamine (SP) Falsified Coartem Combiart reference method TLC from Minilab ® Dimensions: 82 x 63 x 40 mm Weight: ~ 136 g Falsified Duocotecxin Falsified Maloxine Combiart TP : 1 FP : 0 TN :1 FN : 0 Duocotecxin TP : 1 FP : 0 TN :1 FN : 0 Maloxine TP : 1 FP : 0 TN :1 FN : 0 Correct identification of each brand name Falsified Coartem Combiart Falsified Duocotecxin Falsified Maloxine