Under the auspices of the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a key comparison, CCQM K55.b, was coordinated by the Bureau International des Poids et Mesures (BIPM) in 2010/2011. Nineteen national measurement institutes and the BIPM participated. Participants were required to assign the mass fraction of aldrin present as the main component in the comparison sample for CCQM-K55.b which consisted of technical grade aldrin obtained from the National Measurement Institute Australia that had been subject to serial recrystallization and drying prior to sub-division into the units supplied for the comparison.Aldrin was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of organic compounds of medium structural complexity [molar mass range 300 Da to 500 Da] and low polarity (pKOW < −2) for which related structure impurities can be quantified by capillary gas phase chromatography (GC).The key comparison reference value (KCRV) for the aldrin content of the material was 950.8 mg/g with a combined standard uncertainty of 0.85 mg/g. The KCRV was assigned by combination of KCRVs assigned by consensus from participant results for each orthogonal impurity class. The relative expanded uncertainties reported by laboratories having results consistent with the KCRV ranged from 0.3% to 0.6% using a mass balance approach and 0.5% to 1% using a qNMR method.The major analytical challenge posed by the material proved to be the detection and quantification of a significant amount of oligomeric organic material within the sample and most participants relying on a mass balance approach displayed a positive bias relative to the KCRV (overestimation of aldrin content) in excess of 10 mg/g due to not having adequate procedures in place to detect and quantify the non-volatile content—specifically the non-volatile organics content—of the comparison sample.There was in general excellent agreement between participants in the identification and the quantification of the total and individual related structure impurities, water content and the residual solvent content of the sample.The comparison demonstrated the utility of 1H NMR as an independent method for quantitative analysis of high purity compounds. In discussion of the participant results it was noted that while several had access to qNMR estimates for the aldrin content that were inconsistent with their mass balance determination they decided to accept the mass balance result and assumed a hidden bias in their NMR data. By contrast, laboratories that placed greater confidence in their qNMR result were able to resolve the discrepancy through additional studies that provided evidence of the presence of non-volatile organic impurity at the requisite level to bring their mass balance and qNMR estimates into agreement.Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison ...

Este trabalho compara os resultados obtidos na determinação de voláteis (água e solventes residuais) em novos materiais de referência certificados (MRC) ou candidatos a MRC dos ingredientes ativos farmacêuticos (API) captopril, metronidazol, diclofenaco sódico, diclofenaco potássico e furosemida, através do uso de diferentes técnicas: perda por dessecação (LOD), titulação coulométrica tipo Karl Fisher (KF), cromatografia gasosa (injeção por headspace estático) com detector por ionização em chama (sHS-GC-FID) e com espectrômetro de massas (sHS-GC-MS), análise termogravimétrica (TGA) e espectroscopia no infravermelho próximo (NIR) com análise estatística multivariada dos resultados. As três primeiras técnicas levaram a resultados complementares na determinação de voláteis, enquanto as outras duas mostraram pouca sensibilidade para a determinação de voláteis na faixa de concentração avaliada. A perda por dessecação foi considerada a técnica mais apropriada para determinação da fração mássica de voláteis a ser utilizada no cálculo do teor de API por balanço de massa.This work compares the results obtained for the determination of volatiles (water and residual solvents) in new certified reference materials (CRM) or candidate CRMs of the active pharmaceutical ingredients (API) captopril, metronidazole, sodium diclofenac, potassium diclofenac and furosemide, by means of different techniques: loss on drying (LOD), Karl Fischer (KF) coulometric titration, static headspace gas chromatography with flame ionization detection (sHS-GC-FID) and with mass spectrometry (sHS-GC-MS), thermogravimetric analysis (TGA) and near infrared spectroscopy (NIR) with multivariate chemometric analysis of results. The first three methods led to complementary results. The two other techniques were not sufficiently sensitive to determine volatiles in the concentration range evaluated. The loss on drying method was considered the most appropriate to determine the mass fraction of the volatiles to be used in the mass balance calculation of the API mass fraction in the pharmaceutical CRMs.Keywords: volatiles, water, residual solvents, active pharmaceutical ingredient (API), certified reference materials (CRM), analytical quality control IntroductionSeveral are the reasons for determining the mass fractions of water and residual solvents in pharmaceuticals, including their influence on the physicochemical 1-7 and microbiological stability of raw materials and finished products, their potential toxicity [1][2][3]8 and also economic aspects 9 since their presence results in analyte mass fractions smaller than 100%. Residual solvents may be introduced in active pharmaceutical ingredients (API) during their synthesis, especially if the final purification step is carried out by crystallization in different solvents, as well as during drug products formulation and manufacturing. 1,7,8 In the particular case of certified reference materials (CRM) of APIs, the determination of volatiles is essential both to demonstrate the compliance with Pharmacopeial acc...

The Brazilian Metrology Institute (National Institute of Metrology, Quality, and Technology, Inmetro) has been developing a certified reference material (CRM) of the volatile organic compounds benzene; toluene; ethylbenzene; and ortho, meta, and para-xylenes (BTEX) in methanol, to ensure quality control for environmental-analysis measurements. The objective of this paper is to present the results of certification studies: uncertainty estimates related to characterization, a homogeneity study, and a stability study on a single lot of CRM composed of BTEX in methanol. The method used analysis of variance (ANOVA), a statistical tool, to evaluate the homogeneity and stability of the BTEX CRM, which complies with ISO Guide 30 series. The homogeneity and stability of the BTEX CRM was confirmed for all analytes and their respective properties. All the procedures used in this study complied with ISO GUIDE 34, ISO GUIDE 35, and the guide to the expression of uncertainty of measurement (GUM).

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Recebido em 8/9/05; aceito em 7/4/06; publicado na web em 11/8/06 PROFICIENCY ASSAY OF THE DITHIOCARBAMATES IN BANANA PULP ANALYSIS. A proficiency assay of the determination of dithiocarbamate pesticide residues in banana was carried out. Fourteen laboratories participated in this study. Homogeneity and stability testing were performed by INCQS on the samples sent to the laboratories. Analytical results supplied by the pesticide residues laboratory of the VWA/KvW, Amsterdam, Holland, were used to define the designated value for the thiram concentration in the study samples. Results: Fifty percent of the participating laboratories had satisfactory results. Efforts are needed to improve the precision of the analytical results and to decrease the number of false negative results observed.Keywords: pesticides; dithiocarbamates; interlaboratorial. INTRODUÇÃOO Brasil, como um país de extensa área rural e clima favorá-vel, é um dos maiores produtores e exportadores de produtos agrí-colas do mundo. Entretanto, muitos agricultores ainda não seguem as boas práticas agrícolas e, muitas vezes, utilizam agrotóxicos indiscriminadamente, tanto no que se refere à quantidade como à qualidade desses produtos. Tal fato torna-se uma preocupação para a saúde pública, devido aos danos causados ao trabalhador rural e ao consumidor.Os ditiocarbamatos (DTCs) pertencem a um grupo de agrotóxicos organossulfurados empregados na agricultura com ação fungicida. No Brasil existem registrados seis tipos de substâncias da classe dos ditiocarbamatos como ingredientes ativos, para quarenta e um diferentes tipos de cultura 1 .A relevância toxicológica dessas substâncias deve-se a seus dois maiores produtos de degradação, etileno tiouréia (ETU) e propilenotiouréia (PTU), suspeitos de serem bociogênicos, carcinogênicos e mutagênicos em ratos 2,3 . No Brasil, o uso de ditiocarbamatos em culturas é intenso, conforme relatado pelo programa gerenciado pela Agência Nacional de Vigilância Sanitária (ANVISA), o Programa Nacional de Análise de Resíduos de Agrotóxicos em Alimentos (PARA) 4 .O monitoramento de agrotóxicos em alimentos é importante para avaliar os níveis das frutas e verduras produzidas e comercializadas no país; verificar se os limites máximos de resíduos permitidos (LMR) estabelecidos pela legislação brasileira estão sendo de fato respeitados; verificar se agrotóxicos não registrados na ANVISA estão sendo utilizados ilegalmente no país; investigar se agrotóxicos devidamente registrados na ANVISA estão sendo utilizados de forma inadequada e, obter dados mais confiáveis para a estimativa da ingestão diária de resíduos de agrotóxicos pela população, uma informação fundamental ao realizar o registro de novos agrotóxicos e/ ou renovar o registro dos já autorizados 5 .Poucos são os laboratórios que realizam ensaio de determinação de resíduos de agrotóxicos em alimentos no Brasil. Os objetivos das análises realizadas por esses laboratórios normalmente são controle da qualidade de produção, pesquisa, exportação e proteção da saúde pública. Os labora...

This paper aims to present the developments performed by the Brazilian Metrology Institute (NMI) – Inmetro, considering the environmental demand. Inmetro addresses great part of its activities to the study of the traceability transference based on production and dissemination of certified reference material (CRM) of different areas in chemistry. It will be presented results from certification of the following reference materials developed: BTEX and PAH in solution, besides automotive emission gas mixtures and bioethanol. So, the achievements made are the growth in developing CRM, in order to support the needs of the national industry and to disseminate traceability among the society.

This chapter aims to present the developments performed by the Brazilian Metrology Institute (NMI) – Inmetro, considering the environmental demand. Inmetro addresses a great part of its activities to the study of the traceability transference based on production and dissemination of certified reference material (CRM) of different areas in chemistry. The chapter presents results from certification of the following reference materials developed: BTEX and PAH in solution, besides automotive emission gas mixtures and bioethanol. So, the achievements made are the growth in developing CRM in order to support the needs of the national industry and to disseminate traceability among the society.

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