RESUMO
The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA), was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities.
Assuntos
Heparina/normas , Espectroscopia de Ressonância Magnética , Análise de Componente Principal , Espectrofotometria Ultravioleta , Contaminação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Espectroscopia de Ressonância Magnética/métodos , Métodos , Padrões de Referência , Espectrofotometria Ultravioleta/métodosRESUMO
INTRODUCTION: The change in the heparin solution trade mark in Brazil that had been commonly used in cardiac surgery has shown increased number in the coagulopathy, re-exploration and other side effects in our Institution and others. METHODS: All four different heparin solutions available in the Brazilian market were studied in the Connective Tissue Lab, HUCFF, UFRJ and compared to the Liquemine (out of the market) and the international control solution. All samples were evaluated by magnetic nuclear resonance as well as their anticoagulant effectiveness. RESULTS: There were significant differences among them regarding the anticoagulant activity. It was also observed contamination with other dermatan sulfate, samples chemically degraded and with significant change in the molecular weight. CONCLUSION: Among the studied samples, none of them can offer security in cardiac surgeries on pump. None of them has demonstrated similar quality to Liquemine, which is not available in the Brazilian market.
Assuntos
Anticoagulantes/normas , Procedimentos Cirúrgicos Cardiovasculares , Indústria Farmacêutica/normas , Heparina/normas , Anticoagulantes/sangue , Anticoagulantes/química , Brasil , Cromatografia em Gel , Dermatan Sulfato/sangue , Contaminação de Medicamentos , Heparina/sangue , Heparina/química , Ácidos Hexurônicos/sangue , Humanos , Espectroscopia de Ressonância Magnética , Peso Molecular , Tempo de Tromboplastina Parcial , Controle de Qualidade , Padrões de ReferênciaRESUMO
INTRODUÇÃO: A mudança na marca da heparina rotineiramente utilizada nas cirurgias cardíacas no Brasil tem sido acompanhada por aumento do número de casos de discrasia sanguínea, aumento de reoperações e efeitos adversos em nossa Instituição e em outras. MÉTODOS: Foram avaliadas no Laboratório de Tecido Conjuntivo do HUCFF/UFRJ, quatro preparações disponíveis e comparadas à heparina retirada do mercado (Liquemine) e ao padrão de controle internacional. As preparações de heparina foram submetidas à ressonância nuclear magnética para avaliação da integridade estrutural, bem como avaliação de sua eficácia anticoagulante. RESULTADOS: Houve diferença significativa quanto à atividade anticoagulante entre as amostras. Também se observou a presença de contaminação com dermatam sulfato, amostras degradadas quimicamente e com significativa alteração do peso molecular. CONCLUSÃO: Das amostras estudadas, nenhuma atendeu aos requisitos de segurança para utilização em cirurgias cardíacas com circulação extracorpórea. Nenhuma delas apresentou a qualidade semelhante ao Liquemine, não mais disponível no mercado brasileiro.
INTRODUCTION: The change in the heparin solution trade mark in Brazil that had been commonly used in cardiac surgery has shown increased number in the coagulopathy, re-exploration and other side effects in our Institution and others. METHODS: All four different heparin solutions available in the Brazilian market were studied in the Connective Tissue Lab, HUCFF, UFRJ and compared to the Liquemine (out of the market) and the international control solution. All samples were evaluated by magnetic nuclear resonance as well as their anticoagulant effectiveness. RESULTS: There were significant differences among them regarding the anticoagulant activity. It was also observed contamination with other dermatan sulfate, samples chemically degraded and with significant change in the molecular weight. CONCLUSION: Among the studied samples, none of them can offer security in cardiac surgeries on pump. None of them has demonstrated similar quality to Liquemine, which is not available in the Brazilian market.
Assuntos
Humanos , Anticoagulantes/normas , Procedimentos Cirúrgicos Cardiovasculares , Indústria Farmacêutica/normas , Heparina/normas , Anticoagulantes/sangue , Anticoagulantes/química , Brasil , Cromatografia em Gel , Contaminação de Medicamentos , Dermatan Sulfato/sangue , Heparina/sangue , Heparina/química , Ácidos Hexurônicos/sangue , Espectroscopia de Ressonância Magnética , Peso Molecular , Tempo de Tromboplastina Parcial , Controle de Qualidade , Padrões de ReferênciaAssuntos
Humanos , Masculino , Idoso , Heparina/normas , Heparina de Baixo Peso Molecular/normas , Trombocitopenia/induzido quimicamente , Trombose/induzido quimicamente , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Trombocitopenia/etiologia , Trombose/etiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversosAssuntos
Heparina/normas , Academias e Institutos , Animais , Argentina , Padrões de Referência , SuínosRESUMO
In agreement with the Regional Programme of Reference Materials of the Panamerican Health Organization the Instituto Nacional de Farmacología y Bromatología of Buenos Aires designed a study for the calibration of a Reference Material for Heparin, porcine, mucosal and a Reference Material for Heparin, bovine, mucosal. The assay methods used in this study were those described in the United States Pharmacopeia XXI Ed and British Pharmacopoeia 1980, Addendum 1983. The overall combined potency estimates of both heparin in preparations relative to 4th Int.St. was 1633.83 UI/ampoule (95% confidence limits 1609.70-1657.96 UI/ampoule) for porcine heparin and 1332.31 UI/ampoule (95% confidence limits, 1302.31-1361.77 UI/ampoule) for bovine heparin. The assigned unitage was 1630 UI/ampoule for the porcine Reference Material and 1330 UI/ampoule for the bovine Reference Material.
Assuntos
Heparina/normas , Animais , Bovinos , Heparina/análise , América Latina , Padrões de Referência , SuínosRESUMO
Heparin and Concanavalin A complexes were studied under different conditions. Interaction was measured by reading the turbidity at 420 nm. The influence of the pH, heparin, and salt concentration was measured. In the presence of salts pH was very critical, and above pH 5.4 the interaction was practically negligible. At pH 4.6 or 5.2 and the lowest salt concentration compatible with buffering, heparin fractions with different anticoagulant specific activities were detected in the precipitate and in the supernatant, after the interaction. In all cases a significative difference was observed in favor of the heparin isolated from the precipitate. Possibility of an artifact was eliminated by using adequate blanks and running the coagulation tests in the presence of an excess of Concanavalin A.