title: Chromatographic impurity fingerprinting of genuine and counterfeit Cialis® as a means to compare the discriminating ability of PDA and MS detection.
abstract: Public health is threatened worldwide by counterfeit medicines. Their quality, safety and efficacy cannot be guaranteed since no quality control is performed during and/or after the manufacturing process. Characterization of these products is a very important topic. During this study a High Performance Liquid Chromatography-Photodiode Array (HPLC-PDA) and a High Performance Liquid Chromatography - Mass Spectrometry (HPLC-MS) method were developed to analyse both genuine and counterfeit samples of Cialis®. The obtained PDA and MS fingerprints were explored and modelled using unsupervised Principal Component Analysis (PCA) and supervised Partial Least Squares and its discriminant variant (PLS, PLS-DA) as well the classification methods including Soft Independent Modelling of Class Analogy (SIMCA) and the k Nearest Neighbour classifier (kNN). Both MS1 and MS2 data and data measured at 254 nm and 270 nm were used with the aim to test the potential complementarity of PDA and MS detection. First, it was checked if both groups of fingerprints can support differentiation between genuine and counterfeit medicines. Then, it was verified if the obtained multivariate models could be improved by combining information present in MS and PDA fingerprints. Survey of the models obtained for the 254 nm data, 270 nm data and 254_270 nm data combination showed that a tendency of discrimination could be observed with PLS. For the 270 nm data and 254_270 nm data combination a perfect discrimination between genuine and counterfeit medicines is obtained with PLS-DA and SIMCA. This shows that 270 nm alone performs equally well compared to 254_270 nm. For the MS1 and MS1_MS2 data perfect models were obtained using PLS-DA and kNN, indicating that the MS2 data do not provide any extra useful information to acquire the aimed distinction. When combining MS1 and 270 nm perfect models were gained by PLS-DA and SIMCA, which is very similar to the results obtained for PDA alone. These results show that both detectors have a potential to reveal chemical differences between genuine and counterfeit medicines and thus enable the construction of diagnostic models with excellent recognition. However, if a larger sample set, including more possible sources of variation, is analysed more sophisticated techniques such as MS might be necessary.
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmanstraat 14, B-1050 Brussels, Belgium; Research group NatuRA (Natural products and Food-Research and Analysis), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Custers
authors.affiliation: Institute of Chemistry, University of Silesia, 9 Szkolna Street, 40-006 Katowice, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Krakowska
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmanstraat 14, B-1050 Brussels, Belgium.
authors.forename: J O
authors.initials: JO
authors.lastname: De Beer
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmanstraat 14, B-1050 Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Courselle
authors.affiliation: Institute of Chemistry, University of Silesia, 9 Szkolna Street, 40-006 Katowice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Daszykowski
authors.affiliation: Research group NatuRA (Natural products and Food-Research and Analysis), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Apers
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmanstraat 14, B-1050 Brussels, Belgium. Electronic address: Eric.Deconinck@wiv-isp.be.
authors.forename: E
authors.initials: E
authors.lastname: Deconinck
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D058110:Counterfeit Drugs / Q000737:chemistry*; D048088:Informatics; D000069550:Machine Learning; D013058:Mass Spectrometry; D025341:Principal Component Analysis; D000068581:Tadalafil / Q000032:analysis* / Q000737:chemistry
chemical_list: D058110:Counterfeit Drugs; D000068581:Tadalafil
keywords: Chemometrics; Cialis®; Counterfeit medicines; High Performance Liquid Chromatography; Mass spectrometry; Photodiode array detection