1. Identification of Counterfeit Tablets and Authentication of Medicines in the International Wholesaling Supply Chain Using Near-infrared Spectroscopy S. Assi. R. A. Watt and A.C. Moffat The School of Pharmacy 29/39 Brunswick Square, London. [email_address]

2. Introduction : Counterfeit Medicines Identity Active ingredient Source Class

4. Experimental (Materials)

6. Results and Discussion (Spectrum Quality) Near-infrared spectra of 12 scans of (a) Nexium measured by the Smart probe, (b) Nexium measured by the RCA, (c) Protium measured by the Smart Probe and (d) Protium measured by the RCA The RCA has better spectral quality especially beyond 2200 nm.

7. Results and Discussion (Instrumental Noise/Pre-treatment method) Standard deviation of 12 spectra of Protium tablets using the listed pre-treatment methods over the maxima wavelengths. Standard deviation of 12 spectra of Protium 20 mg using the Probe and the RCA

8. Results and Discussion (Optimum Number of Spectra) Diagrammatic representation of 95 % frequency circles for a bi-variate normal distribution used in PCA plots

9. Results and Discussion (Optimum Identification Method) Of the methods applied correlation in wavelength space (CWS) and principal component analysis (PCA) were the best two methods. CWS map of the nine products: Lipitor, Plavix, Nexium, Singulair, Zyprexa, Protium, Seroquel, Risperdal and Effexor respectively. PCA scores plot of the SNV-D2 spectra of the nine products measured by the RCA.

11. Application (Korean and Lebanese samples) SNV-D2 NIR spectra of Bayer’s Ciprobay 250 mg tablet from Lebanon (blue), Bayer’s Ciproxin 500 mg from the UK (red) and Bayer’s Ciproxin 750 mg from the UK (green) which are completely superimposed. Authentic batches (red) and counterfeit batches (blue) of Viagra Tablets 100 mg with the 95% and 99% equal frequency ellipses for the authentic batches.

13. Application (Wholesaler product authentication) NIR spectra of authentic rosiglitazone 4 mg (blue) and test tablets rosiglitazone 4 mg which turned out to be counterfeit (red). When the water regions (1476-1516 nm and 1918-2089 nm) were removed the CWS value dropped from 0.919 to 0.898, so the product still failed. NIR spectra of authentic Dosan 4 mg (blue) and test tablets Dosan 4 mg which turned out to be authentic (red). When the water regions (1476-1516 nm and 1918-2089 nm) were removed the CWS value stayed the same: 0.998.

14. Application (Wholesaler product authentication) NIR average spectra of 10 authentic Atorlip 40 mg tablets (blue) and 10 test tablets Atorlip 40 mg (red). r=0.953 NIR average spectra of 10 authentic Atorlip 40 mg tablets (blue) and 1 test tablet Atorlip 40 mg (red). r= 0.886 In some cases one tablet fails while the average of the whole batch passes and this confirms the need for the use of at least 10 tablets from a single batch.

15. Application (BBC samples) NIR spectra of authentic Viagra 100 mg (blue) and test tablet Viagra 100 mg which turned out to be counterfeit (red). r= 0.95 PCA scores plot of the SNV-D2 NIR spectra of a calibration set of authentic (red) and counterfeit (blue) Viagra 100 mg tablets and a validation set of authentic Viagra 100 mg tablet B.No. 6098203U (green) and counterfeit Viagra 100 mg tablet 1 (magenta) and tablet 2 (cyan). This Viagra tablet is one example how CWS failed to identify a counterfeit and PCA was able to spot it.

16. Application (BBC samples) SNV-D2 NIR spectra of Reductil 15 mg standard B.No. 3300680 (blue) and Reductil 15 mg sample B.No. 311799D (red) capsule contents. r= 0.503 PCA scores plot of the SNV-D2 NIR spectra of authentic Reductil 10 mg (blue) and 15 mg (red) standards and authentic reductil sample 10 mg (green) and counterfeit reductil sample 15 mg (magenta) with the 95% and 99% equal frequency ellipses around the authentic batches