Eleonora Antoniella

Medicines informal market in Congo, Burundi and Angola: counterfeit and sub-standard antimalarials

BackgroundThe presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines.MethodsIn this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed.ResultsThe results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiry date); low content of active substance (in one sample); different, non-declared, active substance (in one sample); sub-standard technological properties and very low dissolution profiles (in about 50% of samples). This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions.ConclusionThis paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution profile can be dramatically affected by the choice of excipients in the oral solid formulation and, in many cases, is out of specifications due to the absence of formulation studies by producers of developing countries.

An LC method for the simultaneous screening of some common counterfeit and sub-standard antibiotics Validation and uncertainty estimation.

Pharmaceutical counterfeiting is a worldwide public health problem, often under-recognised, especially in developing countries where the percentage of counterfeit and sub-standard medicines is dramatically high. Antibiotics, among the most widespread drugs, have been particularly targeted by counterfeiters. World Health Organization emphasizes the need for development and distribution of screening methods explicitly targeted to counterfeit drugs. In this paper is presented a single method for the simultaneous analysis of some of the most common and counterfeited essential antibiotics: ampicillin, amoxicillin+clavulanic acid, doxycycline, cloxacillin, chloramphenicol. A full validation was performed in terms of linearity, precision, robustness and trueness; an assessment of uncertainty was carried out exploiting these data. A wide linearity range was investigated considering the specific nature of counterfeit and sub-standard drugs, whose content in active substance may be rather far from the declared amount. A large span in robustness parameters was considered and a complete intermediate precision assessment was conducted, envisaging the possibility of transferring the method to quality control laboratories, hopefully in developing countries. Finally, the method was successfully applied to the analysis of antibiotics purchased on the informal market in Chad, among which counterfeit and sub-standard samples were detected.

Characterization of Sildenafil analogs by MS/MS and NMR: A guidance for detection and structure elucidation of phosphodiesterase-5 inhibitors

Novel synthetic analogs of Sildenafil are constantly detected as adulterants in counterfeit drugs and dietary supplements. Their intake constitutes a serious health hazard as side effects are unknown. In this paper an investigation is carried out on NMR and MS/MS spectra of Sildenafil, Thiosildenafil, Acetildenafil and thirteen of their analogs: a list of key signals is reported and discussed with the intent to provide a tool that can help in detecting adulteration and in elucidating the structure of novel analogs. In this view extensive spectral data were reported, discussed and summarized in tables. A discussion on mass fragmentation and NMR chemical shifts is also provided to rationalize assignation. Moreover, a comprehensive information on the route of synthesis is provided for the benefit of those medicines control laboratories that need to synthesize analogs reference standards in-house.

A Survey on Illegal and Counterfeit Medicines for the Treatment of Erectile Dysfunctions in Italy

INTRODUCTION In developed countries the phenomenon of pharmaceutical counterfeiting is steadily increasing through the illegal and the Internet market. Medicines for the treatment of erectile dysfunctions containing phosphodiesterase type 5 inhibitors (PDE5) are especially prone to falsification. AIMS To obtain evidence of the health risks for patients taking these products and to provide useful information to general practitioners and specialists in sexual medicine. METHODS First the samples were visually inspected and then analyzed to get information about their identity and quality. MAIN OUTCOME MEASURES A survey on the PDE5 medicines analyzed by the Italian official medicines control laboratory between 2005 and 2011 was performed. All the analyzed medicines were gathered from the Italian illegal market (seizures by police forces) or were bought from illegal online pharmacies. Results.  The study revealed that 24% of the analyzed samples were counterfeit and 54% were illegal medicines. In 12% of the cases an intermediate classification (illegal/counterfeit) was assigned. Only 7% of the samples were original. Moreover, the examination of the packaging evidenced potential risks: outer and immediate packaging missing; inconsistency between the carton box and the blister as regards the expiry date and/or the batch number; expiry date or manufacturers name or country missing. CONCLUSIONS In 19% of the samples a potential health risk for patients was identified due to either the presence in the sample of more than one undeclared PDE5(s) or an amount of the active ingredient higher than that declared (up to 190% of the maximum dose) or to the presence of potentially dangerous excipients of non-pharmaceutical origin or quality (e.g., gypsum or non-purified talc).

Different crystal morphologies arising from different preparation methods of a same polymorphic form may result in different properties of the final materials: the case of diclofenac sodium trihydrate.

Diclofenac sodium is a nonsteroidal anti-inflammatory drug widely used in painful and inflammatory diseases. It can exist in different hydrate phases. Recently the physico-chemical and pharmaceutical properties of a trihydrate form, named DSH3 were reported by the same authors. This short communication discusses how samples of a same polymorphic form can display dissimilar analytical signatures when obtained by different routes. Data from hot-stage microscopy, FT-IR spectroscopy, X-ray powder diffraction (XRDP) and thermal analysis were used to characterise the DSH3 samples prepared by different methods. Through the case study of diclofenac sodium, this work highlights how the method used to prepare a specific crystal modification can generate samples with different morphologies and therefore different properties and physical stability.

Counterfeit Adderall Containing Aceclofenac from Internet Pharmacies.

A nontargeted approach based on liquid chromatography equipped with a quadrupole time‐of‐flight mass detector (LC‐MS Q‐TOF) joined to nuclear magnetic resonance (NMR) analysis allowed rapid identification and quantification of the anti‐inflammatory drug aceclofenac in illegal Adderall tablets. The largest chromatographic peak had m/z = 354.030 and m/z = 376.012 matching, respectively, the ionic structures (M + H)+ and (M + Na)+ of a molecule M. The accurate mass data generated the molecular formula C16H13Cl2NO4. A screening of the pharmaceutical active substances having that molecular formula together with the MS/MS fragmentation pattern suggested aceclofenac. Aceclofenac structure was unambiguously confirmed by 1H and 13C NMR experiments. The aceclofenac content was 90 mg/tablet (RSD 2%) as detected by quantitative NMR. Information on the identity and content of illegal drugs is required for legal purposes; it supports in evaluating the effective impact on users safety, and it is useful for control laboratories using a targeted approach in their analytical activities.