Betamethasone in cyclodextrin in deformable liposomes for cutaneous applications: development and diffusion studies

Conference (2009, May 14)

Betamethasone in cyclodextrin in deformable liposomes for topical applications: absorption studies using pig skin

Poster (2009, April 01)

Moisture content determination of pharmaceutical pellets by near infrared spectroscopy: method development and validation.

in Analytica Chimica Acta (2009), 642(1-2), 186-92

The aim of the present study was to develop and validate a near infrared method able to accurately determine a moisture content of pharmaceutical pellets ranging from 1% to 8% in order to check their ... [more ▼]

The aim of the present study was to develop and validate a near infrared method able to accurately determine a moisture content of pharmaceutical pellets ranging from 1% to 8% in order to check their moisture content conformity. A calibration and validation set were designed for the conception and evaluation of the method adequacy. An experimental protocol was then followed, involving two operators, independent production campaign batches and different temperatures for data acquisition. On the basis of this protocol, prediction models based on partial least squares (PLS) regression were then carried out. Conventional criteria such as the R(2), the root mean square errors of calibration and prediction (RMSEC and RMSEP) as well as the number of PLS factors enabled the selection of three preliminary models. However, such criteria did not clearly demonstrate the model's ability to give accurate predictions over the whole analyzed water content range. Consequently, a novel approach based on accuracy profiles which allow the selection of the most fitted model for purpose was used. According to this novel approach, the model using multiplicative scatter correction (MSC) pre-treatment was obviously the most suitable. Indeed, the resulting accuracy profile clearly showed that this model was able to determine moisture content over the range of 1-8% with a very acceptable accuracy. The present study confirmed that NIR spectroscopy could be used in the PAT concept as a non-invasive, non-destructive and fast technique for moisture content determination in pharmaceutical pellets. In addition, facing the limit of the classical and commonly used criteria, the use of accuracy profiles proved to be useful as a powerful decision tool to demonstrate the suitability of the proposed analytical method. [less ▲]

Analytical validation based on total error measurement and cut-off interpretation of a neonatal screening TSH-immunoassay.

in Journal of Chromatography. B : Analytical Technologies in the Biomedical & Life Sciences (2009), 877

To prevent the severe developmental and physical morbidities associated with congenital hypothyroidism, we developed a home-made Enzyme-Linked Immunosorbent Assay (ELISA) method to quantify Thyroid ... [more ▼]

To prevent the severe developmental and physical morbidities associated with congenital hypothyroidism, we developed a home-made Enzyme-Linked Immunosorbent Assay (ELISA) method to quantify Thyroid Stimulating Hormone (TSH) levels on newborn dried blood spots. In order to agree with actual clinical laboratory quality referential (ISO 15189), we desired to update our analytical validation protocol. For this purpose, an approach using accuracy profiles based on tolerance intervals for the total error measurement was for first time applied to an immunological assay. According to acceptance limits fixed at +/-30%, the method was found accurate over a concentration range from 17.48 to 250mIU/L. Based on 99.5 percentile of a 16,459 newborn population, cut-off was fixed at 20.1mIU/L and validated against normal and pathologic neonatal populations. Additionally, uncertainty regions around this value were obtained applying four different approaches. Finally, we demonstrated here our in-house immunological technique fulfils criterions of a neonatal screening policy. [less ▲]

Nouvelle méthodologie pour le développement automatisé de méthodes analytiques en chromatographie liquide pour l’analyse de mélanges de composés inconnus

in Spectra Analyse (2009), 268

Nowadays, many strategies to optimize chromatographic methods are available. However, the development of chromatographic methods remains the most limiting step in the process of synthesis or ... [more ▼]

Nowadays, many strategies to optimize chromatographic methods are available. However, the development of chromatographic methods remains the most limiting step in the process of synthesis or identification of new molecules that could lead to therapeutic agents or new biomarkers despite the availability of new technologies both in chemistry (chemical combinatorial, high throughput screening...) and in analytical biochemistr y (proteomics, metabolomics, herbal ... fingerprinting). Therefore, the aim of this study is to test a new methodology for developing automated chromatographic methods combining experimental planning, independent component analysis, analysis of predictive error propagation and multiple linear regression modeling. Finally, this automated methodology has enabled us to successfully separate the components of an unknown mixture. [less ▲]

A risk-based analysis of the AAPS conference report on quantitative bioanalytical methods validation and implementation.

in Journal of Chromatography. B : Analytical Technologies in the Biomedical & Life Sciences (2009), 877(23), 2235-43

The 3rd American Association of Pharmaceutical Scientists (AAPS)/Food and Drug Administration (FDA) Bioanalytical workshop in 2006 concluded with several new recommendations regarding the validation of ... [more ▼]

The 3rd American Association of Pharmaceutical Scientists (AAPS)/Food and Drug Administration (FDA) Bioanalytical workshop in 2006 concluded with several new recommendations regarding the validation of bioanalytical methods in a report published in 2007. It was aimed to conciliate or adapt validation principles for small and large molecules and an opportunity to revisit some of the major decision rules related to acceptance criteria given the experience accumulated since 1990. The purpose here is to provide a "risk-based" reading of the recommendations of 3rd AAPS/FDA Bioanalytical Workshop. Five decision rules were compared using simulations: the proposed pre-study FDA and Total Error Rules, the rules based on the beta-Expectation Tolerance and beta-gamma-Content Tolerance Interval and, finally, the 4-6-20 rule for in-study acceptance of runs. The simulation results demonstrated that the beta-Expectation Tolerance Rule controls appropriately the risk. The beta-gamma-Content Tolerance Interval was found to be too conservative, depending on the objective, and to lead to a high rate of rejection of procedures that could be considered as acceptable. On the other side, the FDA and the AAPS/FDA workshop Total Error Rule, combined or not, did not achieve their intended objective. With these rules, the risk is high to deliver results in study that would not meet the targeted acceptance criteria. This can be explained because, first, there is confusion between the quality of a procedure and the fitness of purpose of the results it could produce and, second, between the initial performances of a procedure, for example evaluated during pre-study validation and the quality of the future results. [less ▲]

Universal applicability of Total Error for the validation of bioanalytical methods

Conference (2009)

An innovative universal strategy using Total Error is thus proposed to decide about the method’s validity that controls the risk of accepting an unsuitable assay together with the ability to predict the ... [more ▼]

An innovative universal strategy using Total Error is thus proposed to decide about the method’s validity that controls the risk of accepting an unsuitable assay together with the ability to predict the reliability of future results. Several examples of applications of this validation methodology to various types of assays [LC-MS, ELISA, Bio-Assays] will be presented. [less ▲]

Validation of bioanalytical methods using total error

Conference (2009)

Dosage d'oxytétracycline dans les secrétions nasales de porcs par chromatographie liquide : comparaison d'associations de méthodes de préparations d'échantillons et de modes de détection

Poster (2009)

L'erreur totale pour le transfert de méthodes

Conference (2009)