The chemoselective reduction of nitro compounds: scope of the electrochemical method

The selective electrohydrogenation of nitro aliphatic and nitro aromatic functional groups in molecules containing other groups that are easy to hydrogenate (activated double bond, carbon-iodine bond, nitrile,) has been sucessfully carried out in slightly acidic (pH = 3) or neutral (pH = 5-6) methanol-water solutions at Devarda copper and Raney cobalt electrodes. The electrochemical synthesis of a quinolone 15 and a quinoxaline 18 is also reported. Preliminary results on the preparative electroreduction of 5-nitroindole 21 on Hg in aqueous methanol with HBr as supporting electrolyte are presented and dicussed for the first time

New advances in method validation and measurement uncertainty aimed at improving the quality of chemical data

The implementation of quality systems in analytical laboratories has now, in general, been achieved. While this requirement significantly modified the way that the laboratories were run, it has also improved the quality of the results. The key idea is to use analytical procedures which produce results that fulfil the users' needs and actually help when making decisions. This paper presents the implications of quality systems on the conception and development of an analytical procedure. It introduces the concept of the life-cycle of a method as a model that can be used to organize the selection, development, validation and routine application of a method. It underlines the importance of method validation, and presents a recent approach based on the accuracy profile to illustrate how validation must be fully integrated into the basic design of the method. Thanks to the beta-expectation tolerance interval introduced by Mee (Technometrics (1984) 26(3):251-253), it is possible to unambiguously demonstrate the fitness for purpose of a new method. Remembering that it is also a requirement for accredited laboratories to express the measurement uncertainty, the authors show that uncertainty can be easily related to the trueness and precision of the data collected when building the method accuracy profile

Early symptomatic neurosyphilis and ocular syphilis: A comparative study between HIV-positive and HIV-negative patients

International audienceObjectives: Since the 2000s, there has been an increase in prevalence of neurosyphilis (NS) and ocular syphilis (OS). As data about symptomatic NS/OS is limited, this study aims to assess the characteristics of symptomatic NS/OS, according to HIV status.Methods: We compared the clinical and biological presentation of early symptomatic NS/OS and its outcome in HIV-positive and HIV-negative patients.Results: Ninety-six patients (93% men, 49% HIV-positive) were included from 2000 to 2016 in two centers, with 67 (69%) having OS, 15 (16%) NS, and 14 (14%) both. HIV-positive patients were younger (P = 0.006) and more likely to be males having sex with males (P = 0.00048) or to have a history of syphilis (P = 0.01). Among 81 OS, there were 43 posterior uveitis (57%), and bilateral involvement was more common in HIV-positive patients (62% versus 38%, P = 0.045). Among 29 NS there were 21 cases of cranial nerve involvement (72%), seven meningitis (24%) and 11 paresthesia (38%). Involvement of the VIIIth cranial nerve was the most common (16 cases). Treponemal tests were more commonly found positive in cerebrospinal fluid in HIV-positive patients (88% versus 76%, P = 0.04). Visual acuity (VA) always improved after treatment (initial VA logMAR 0.8 ± 0.8 versus 0.1 ± 0.1 at 3 months), but 32% and 18% of the patients still had neurological or ocular impairment respectively six and 12 months after treatment. Non-treponemal serological reversion was observed in 43/50 patients (88%) at six months.Conclusion: HIV infection has no consequence on the outcome of NS and OS. Sequelae are common, emphasizing the importance of prevention, and screening, and questioning enhanced treatment

Critical analysis of several analytical method validation strategies in the framework of the fit for purpose concept.

Analytical method validation is a mandatory step at the end of the development in all analytical laboratories. It is a highly regulated step of the life cycle of a quantitative analytical method. However, even if some documents have been published there is a lack of clear guidance for the methodology to follow to adequately decide when a method can be considered as valid. This situation has led to the availability of several methodological approaches and it is therefore the responsibility of the analyst to choose the best one. The classical decision processes encountered during method validation evaluation are compared, namely the descriptive, difference and equivalence approaches. Furthermore a validation approach using accuracy profile computed by means of beta-expectation tolerance interval and total measurement error is also available. In the present paper all of these different validation approaches were applied to the validation of two analytical methods. The evaluation of the producer and consumer risks by Monte Carlo simulations were also made in order to compare the appropriateness of these various approaches. The classical methodologies give rise to inadequate and contradictory conclusions which do not allow them to answer adequately the objective of method validation, i.e. to give enough guarantees that each of the future results that will be generated by the method during routine use will be close enough to the true value. It is found that the validation methodology which gives the most guarantees with regards to the reliability or adequacy of the decision to consider a method as valid is the one based on the use of the accuracy profile

Example of application of the new strategy proposed for the validation of chromatographic bioanalytical methods

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Méthodes chromatographiques de dosage dans les milieux biologiques : exemple d'application de la stratégie de validation - Rapport d'une commission SFSTP

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Méthodes chromatographiques de dosage dans les milieux biologiques : stratégie de validation - Rapport d'une commission SFSTP

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