Comparison between counterfeit and authentic medicines: A novel approach using differential scanning calorimetry and hierarchical cluster analysis.

Erectile dysfunction medicines such as Cialis and Viagra are very popular worldwide and are between the most prevalent counterfeit medicines in Brazil. A range of analytical methods has been used to analyze Cialis and Viagra, such as ATR-FTIR, GCMS and UPLC-MS. Until now, there are no data available of DSC methods for analysis of counterfeit medicines of Cialis and Viagra. DSC is a thermal analysis that provides useful information of physico-chemical events, and however is almost not used for forensic purposes. In this study, thermal analysis of 25 counterfeit Viagra and Cialis seized by Brazilian Federal Police were performed by DSC and compared to their authentic medicines and analytical standards, along with chemometric tools. Authentic samples of Viagra displayed a similar thermal profile with the API, while Cialis were different with additional endothermic peaks, that could be related to excipients interference. Thermograms of Viagra counterfeit samples were similar to authentic samples, while Cialis showed an enlargement and displacement of endothermic peaks. Also, some Cialis counterfeit samples showed melting peaks attributed to sildenafil, the API of Viagra, instead tadalafil, confirming previous results obtained by UPLC-MS. Multivariate analysis with application of Hierarchical Cluster Analysis classified different groups of samples, including a cluster with counterfeit Cialis and Viagra, indicating the use of same API for both counterfeit medicines and possibly the same illicit production; and a cluster with authentic Viagra and counterfeit Cialis, confirming the addition of sildenafil instead tadalafil to Cialis counterfeit samples. Here for the first time we described the use of DSC for chemical profiling of Cialis and Viagra and showed that even when applied to a small group of samples, DSC along with chemometric tools can be considered as a good auxiliary method in forensic casework samples. DSC provided useful data to perform the identification of counterfeit and authentic medicines, with low cost and a simple method.

Simulation Strategies for Characterizing Phosphodiesterase-5 Inhibitors in Botanical Dietary Supplements.

A novel "Prediction and Confirmation" (PC) strategy was proposed for characterizing phosphodiesterase-5 inhibitor (PDE-5) derivatives in botanical dietary supplements (BDSs) for on-site detection. Discovery Studio (DS) and density functional theory (DFT) calculations were used for the "Prediction" step in order to estimate PDE-5 derivative structures and theoretical Raman shifts without synthesizing the derivatives. After 11 potentially bioactive sildenafil derivatives were acquired through DS, 32 common calculated Raman shifts were obtained through DFT. The mean absolute wavenumber deviation (δ, peak range) of the major bands and the minimum number (τ) of Raman spectral peaks matching the calculated common shifts were optimized, so that a positive result of an unknown sample could be reasonably produced. In this study, δ was set at ±10 cm-1 and the corresponding τ was set at 4-5 after optimization. Surface plasmon resonance (SPR) biosensor and surface-enhanced Raman scattering (SERS) detection were the "Confirmation" step to validate the reliability and accuracy of DS and DFT in the "Prediction" step, respectively. The optimized δ and τ criteria were used as indexes for on-site SERS detection after thin-layer chromatographic (TLC) separation of six real-world samples, one of which was preliminarily identified as "suspected positive samples." This strategy allows for a quick determination of the BDSs adulterated with sildenafil or its derivatives, independent of any standard materials.

Verification of the authenticity of drugs by means of NMR relaxometry-Viagra® as an example.

1H spin-lattice Nuclear Magnetic Resonance (NMR) relaxometry, vibrational spectroscopy and Atomic Force Microscopy (AFM) have been applied to differentiate between original and counterfeit Viagra®. The relaxation studies have been performed in a frequency range covering four orders of magnitude, from 4kHz to 40MHz. It has been shown that for the counterfeit product the relaxation is bi-exponential in the whole frequency range, while for the original Viagra® the relaxation process is always single exponential. Thus, even a qualitative analysis of the relaxation data makes it possible to identify the falsified medicine. Moreover, it has been demonstrated that vibrational spectroscopy does not allow for differentiating between the products, while AFM studies are likely to lead one to deceptive conclusions regarding the originality of the medicine. Furthermore, a quantitative analysis of the relaxation data has been performed to describe in detail the relaxation properties of the original and falsified products.

Evaluation of the residual solvent content of counterfeit tablets and capsules.

A group of counterfeit samples of Viagra and Cialis were screened for their residual solvent content and compared to the content of the genuine products. It was observed that all counterfeit samples had higher residual solvent contents compared to the genuine products. A more diverse range of residual solvents was found as well as higher concentrations. In general these concentrations did not exceed the international imposed maximum limits. Only in a few samples the limits were exceeded. A Projection Pursuit analysis revealed clusters of samples with similar residual solvent content, possibly enabling some future perspectives in forensic research.

VICTORY project: a study of counterfeit PDE5 inhibitor (sildenafil) in Indonesia.

AIM: to quantify the extent of counterfeit sildenafil in Indonesia. METHODS: the study was conducted in 4 big areas: Jakarta, Bandung, East Java (Surabaya and Malang), and Medan. Sildenafil 100 mg tablets were purchased from pharmacies, drugstores, street peddlers, and 3 Indonesian websites. The outlets were chosen by random sampling in each stratum (type of outlet). Sildenafil tablets purchased were sent to Pfizer Quality Operations Division, Dalian, China, for authenticity evaluations (by infra red spectral analysis). All counterfeit tablets were then sent to Pfizer Counterfeit Medicines Laboratory, Sandwich, UK, a portion of which were analyzed quantitatively for sildenafil concentration per tablet (by HPLC). RESULTS: a total of 518 sildenafil 100 mg tablets were collected and sent to Dalian. Of these tablets, 284 tablets (55%) were genuine sildenafil and 234 tablets (45%) were counterfeit sildenafil. Counterfeit sildenafil were mostly found in street peddlers (100%), in drugstores (56%), and from internet (33%), but pharmacies also had (13%) counterfeit sildenafil. The sildenafil content of 106 counterfeit tablets analyzed varied from 24 to 157 mg per 100 mg tablet. No analysis was done to determine other active ingredient. CONCLUSION: 45% sildenafil 100 mg tablets in Indonesia were found counterfeit and widely distributed in street peddlers, drugstores, and pharmacies. This report is aimed to alert the potential consumers, health professionals and regulators of this problem.

Analysis of counterfeit Cialis® tablets using Raman microscopy and multivariate curve resolution.

Counterfeit medicines have become a serious global problem. Consequently, analytical and pharmaceutical scientists have been active in developing and applying new methodologies to detect and analyze counterfeit medicines. Vibrational spectroscopy combined with chemometric methods is becoming a popular choice in this area of research. In this study, Raman microscopy was used to collect chemical images of counterfeit tadalafil tablets and multivariate curve resolution (MCR) was used to analyze the Raman spectra and reveal the identities of the excipients and active pharmaceutical ingredients (API) in each tablet. Resolved counterfeit tablet spectra were compared to the resolved genuine tablet spectra. Both similarities and dissimilarities were revealed by the analysis in terms of the identity of the excipients, the quantity of the API, and the distribution of the components. It was concluded that Raman microscopy combined with MCR is a powerful method to detect and analyze counterfeit tablets.

Counterfeiting of drugs in Brazil.

OBJECTIVE: To identify the main counterfeit drugs seized by the Brazilian Federal Police and the states where seizures have been made. METHODS: A retrospective descriptive study on expert reports produced by criminal investigators of the Federal Police between January 2007 and September 2010, in relation to counterfeit drugs, was carried out. RESULTS: The drugs with greatest numbers of seizures were selective phosphodiesterase-5 inhibitors that are used for treating male erectile dysfunction (Cialis® and Viagra®, mean = 66% ), followed by anabolic steroids (Durateston® and Hemogenin®: 8.9% and 5.7%, respectively). The greatest proportions of the counterfeit drugs were seized in the states of Paraná, Santa Catarina (both Southeastern Brazil) and São Paulo (Southeastern), and the number of non-authentic drugs sent for investigation increased by more than 200% over the study period. There were increases in seizures of smuggled drugs found together with counterfeit drugs: 67% of the seizures included at least one smuggled drug. CONCLUSIONS: Counterfeiting of drugs is a severe public health problem. Identification of the classes of counterfeit drugs present in Brazil and the main Brazilian states with this problem may facilitate future preventive and suppressive actions by the Brazilian bodies responsible for such actions.