The fixed-dose combination artesunate (AS)–amodiaquine (AQ) is one of the most widely used treatments for uncomplicated falciparum malaria. It is currently proposed to the inclusion in the model list of essential medicines of World Health Organization and has been recently prequalified. Until now, no satisfactory method for the simultaneous determination of the two active ingredients had been available. Thus, a reversed phase high performance liquid chromatography for the quantitative determination of AQ and AS was developed and validated. Chromatography was performed using an end-capped octadecylsilyl silica gel column (100 × 4.6 mm, 3 μm) with a binary gradient using aqueous phase containing potassium dihydrogen phosphate (10 mM) and acetonitrile. Taking into consideration the physico-chemical characteristics of the two compounds related to their ionization, the use of a counter ion was necessary to ensure the retention of AQ in a reversed phase system simultaneously to AS. Thus, aqueous mobile phase was adjusted to pH 3.0 and the chosen counter ion was sodium 1-octanesulfonate (100 mM). In these conditions, the retention times were about 4 min for AQ and 10 min for AS with UV detection at 300 and 210 nm, respectively. Method was then validated according to ICH guideline (specificity/linearity/accuracy/precision) and potential interferences with excipients and degradation products were checked. It has also been used for an interlaboratory study involving seven African National Quality Control Laboratories and Afssaps (Agence française de sécurité sanitaire des produits de santé) laboratory. The results demonstrate that this rapid and simple method can be easily used by official laboratories for routine control, market survey and for the detection of potential substandard medicines which are very frequent in African countries.

The presence on the market of illegal products for slimming purposes or the treatment of overweight is a public health issue. These products may contain illicit chemicals in order to improve their effectiveness. Some of these weight-loss compounds are responsible for adverse events, including fatal outcomes. A general strategy for the analysis of any suspect formulation begins with a large screening for the general search of a wide range of compounds. A methodology for the qualitative and quantitative determination of 34 compounds in slimming preparations (such as dietary supplements or medicinal products) was used for the control of slimming formulations from the market, including over the Internet. The fast liquid chromatography system (ultra-high-pressure liquid chromatography) used a gradient of solvent (phosphate buffer and acetonitrile), a C18 endcapped column and a diode array detector. This system allows dual identification based on retention time and UV spectra. The analytical method is simple, fast and selective since 34 weight-loss compounds can be detected in a 15-min run time. Thus, 32 commercial slimming formulations were analysed using this method, allowing the detection and quantification of hazardous active substances: caffeine, clenbuterol, nicotinamide, phenolphthalein, rimonabant, sibutramine, didesmethylsibutramine, synephrine and yohimbine.

This study was initiated by the laboratories and control department of the French Health Products Safety Agency (AFSSAPS) as part of the fight against the public health problem of rising counterfeit and imitation medicines. To test the discriminating ability of Near InfraRed Spectroscopy (NIRS), worse cases scenarios were first considered for the discrimination of various pharmaceutical final products containing the same Active Pharmaceutical Ingredient (API) with different excipients, such as generics of proprietary medicinal products (PMP). Two generic databases were explored: low active strength hard capsules of Fluoxetine and high strength tablets of Ciprofloxacin. Then 4 other cases involving suspicious samples, counterfeits and imitations products were treated. In all these cases, spectral differences between samples were studied, giving access to API or excipient contents information, and eventually allowing manufacturing site identification. A chemometric background is developed to explain the optimisation methodology, consisting in the choices of appropriate pretreatments, algorithms for data exploratory analyses (unsupervised Principal Component Analysis), and data classification (supervised cluster analysis, and Soft Independent Modelling of Class Analogy). Results demonstrate the high performance of NIRS, highlighting slight differences in formulations, such as 2.5% (w/w) in API strength, 1.0% (w/w) in excipient and even coating variations (<1%, w/w) with identical contents, approaching the theoretical limits of NIRS sensitivity. All the different generic formulations were correctly discriminated and foreign PMP, constituted of formulations slightly different from the calibration ones, were also all discriminated. This publication addresses the ability of NIRS to detect counterfeits and imitations and presents the NIRS as an ideal tool to master the global threat of counterfeit drugs.

Ethyl methanesulfonate (EMS) is a potential human mutagenic and carcinogenic compound which has been found by Roche laboratories in nelfinavir mesylate, the active pharmaceutical ingredient of Viracept. In order to verify the quality of the medicinal product, a gas chromatographic method using mass spectrometry detection was developed for the trace analysis of EMS in Viracept 250 mg tablets from Roche laboratories. Combined with suitable sample preparation including a liquid/liquid extraction this method allows the EMS quantification with a reporting limit of 5 ppm. The extract is injected on a gas chromatographic system with a CP624-CB capillary column. Selected Ion Monitoring mode was used for the EMS quantification. Some validation elements of the method are reported. The validation study was performed over a range from 5 ppm to 100 ppm.

Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers.