Application progress of radiolabeled drugs in new drug research and development in China / 药学学报

The metabolism study of radiolabeled drugs plays an important role in the development of new drugs. It provides information on drug absorption, metabolism, tissue distribution and excretion, and plays an irreplaceable role in the metabolite safety evaluation and mass balance of new drugs. The new guidance draft on clinical trials of radiolabeled drugs recently released by the US FDA puts forward higher standards and has been widely concerned by the industry. In recent years, in the research and development of new drugs in China, 14C labeled drugs have been used to carry out clinical metabolism studies, which has overcome key technical bottlenecks and accumulated experience. This paper summarizes the above research progress, analyzes the existing problems, and preliminarily looks forward to the future technological development and application.

Simulación de la dinámica de la biomasa en plancton de un embalse colombiano tropical andino de alta montaña / Simulation of biomass dynamics in plankton of a high-altitude andean tropical reservoir in colombia

ABSTRACT The understanding of the relationships between the planktonic communities in a reservoir allows us to infer possible changes in the redistribution of matter and energy flows in these systems. This work proposes a dynamic model for the trophic network of the Riogrande II tropical reservoir, which integrates the planktonic trophic chains of detritus and grazing, limiting the prey-predator interactions by introducing the prey meeting factor (pmf). We built a dynamic model of mass balance supported by an extensive bibliographic search. The limitations of consumers and resources were represented simultaneously by means of the pmf. The data used to validate the model were compiled from previous investigations carried out in this reservoir from 2010 to 2013. The values of pmf that we found in each simulation suggest that the top predator can access its main prey in certain concentrations of total phosphorus, with a probability of encounter ranging from 9.3 % to 17.7 %. Our simulations indicate that most of the primary production is poorly used by the primary consumers in the photic zone, however, it enters in the flows of the detrital chain and supports the production of zooplankton almost entirely. According to this finding, the biomass densities obtained in the previous studies can be better explained by the causal relationships assumed in this model.

RESUMEN Entender las relaciones entre las comunidades planctónicas en un embalse nos permite inferir posibles cambios en la redistribución de los flujos de materia y energía en este sistema. Este trabajo propone un modelo dinámico para representar la red trófica del embalse tropical Riogrande II, donde se integran las cadenas tróficas de pastoreo y detritus y se limitan las interacciones entre predadores, presas y recursos al introducir un factor limitante de encuentro con la presa (pmf). El modelo dinámico se enfoca en el balance de masas sustentado en una amplia búsqueda bibliográfica. Los datos usados para validar el modelo se colectaron de datos previamente reportados para el embalse durante los años 2010 y 2013. Los valores de pmf obtenidos en cada simulación, sugieren que el predador dominante puede acceder a su presa principal a ciertas concentraciones de fósforo total, con una probabilidad de encuentro que va desde 9,3 % hasta 17,7 %. Nuestros resultados indican que la mayor parte de la producción primaria es poco aprovechada por los consumidores en la zona fótica, sin embargo, ingresa en el flujo de la cadena detrítica de manera que soporta la producción de zooplancton casi por completo. Las relaciones causales asumidas en este modelo explican en gran medida las densidades de biomasa reportadas en estudios previos.

Establishment of national reference standard of tazobactam impurity A / 中国药科大学学报

@#To improve the standard of quality control of tazobactam and its preparations in China, national reference standard of tazobactam impurity A was developed. After tazobactam impurity A was synthesized, its structure was validated by infrared (IR), mass spectrometry (MS) and nuclear magnetic resonance (NMR), and its content uniformity and short-term stability were measured and investigated. Then, water content and residue on ignition of impurity A were determined, and its purity was determined using high performance liquid chromatography (HPLC) with 10 mmol/L ammonium acetate solution-acetonitrile (98∶2) as the mobile phase. Mass balance method was used to determine the content of the first batch of tazobactam impurity A national standard substance. Meanwhile, nuclear magnetic quantitative method was used to calculate the content, which was mutually verified with the mass balance method. The developed reference material of tazobactam impurity A is consistent with the maximum degradation impurity in tazobactam system applicability solution and the reference material of tazobactam related substance A contained in USP41. Within the 95% confidence range, the ratio of inter- and intra-bottle variance of impurity A after separation was 0.61 (< F0.05(11,12)), proving that the uniformity was satisfying. The contents of organic impurity, water content and inorganic impurity in impurity A were 0.90%, 1.24% and 0.25%, respectively. The content of impurity A was determined to be 97.6% by mass balance method, which was basically consistent with the result of nuclear magnetic quantitative method (97.1%). Under the condition of 25 °C, the area normalized purity of impurity A was 99.1% at 0, 3, 5 and 10 days, proving that the sample was stable at room temperature for 10 days. Finally the first batch of national standard substance of tazobactam impurity A was established successfully.

Progress in Development of Human Radiolabelled Mass Balance and Biotransformation Studies / 中国药学杂志

Recently, with the rapid development of new drug research in China, the human mass balance and biotransformation (MBB) studies on innovative drugs are on a track to become indispensable during new drug application. However, traditional analysis method, e.g. mass spectrum, is insufficient to elaborately explain the mass balance and the relative biotransformation of the investigated drugs in human bodies. This problem could be solved by applying radiolabelled technique into these MBB studies, which are more and more popular nowadays. The authors' hospital is one of the first a few organizations to conduct the MBB studies, and has completed almost 20 trials. This review mainly focused on the study design from the investigators' viewpoints, involving the related rules and regulations, both at home and abroad, and the protocol design, so as to provide our thinkings for references and benefit to the new drug clinical trial in the future.

Balanço de fósforo e nitrogênio em leitos cultivados com Eichhornia crassipes (Mart.) Solms / Phosphorus and nitrogen balance in constructed wetlands with Eichhornia crassipes (Mart.) Solms

RESUMO O descarte incorreto de resíduos, mesmo após tratamento, pode causar impactos negativos nos corpos d'água receptores. Em especial, substâncias como nitrogênio e fósforo podem se tornar, em função de suas concentrações, tóxicas para os organismos aquáticos ou produzir condições favoráveis à proliferação de vegetação, que podem iniciar os processos de eutrofização. Leitos cultivados são sistemas de tratamento de esgoto construídos com a finalidade de imitar a estrutura das wetlands naturais, promovendo mecanismos de fitorremediação. Apesar de a Eichhornia crassipes ser uma planta invasiva causadora de problemas em rios e lagos eutrofizados, seu uso pode ser interessante em leitos cultivados, pois é uma planta ornamental, o que aumentará a aceitação do sistema de tratamento de águas residuárias, além de poder ser reutilizada no artesanato, na produção de biocombustível e na alimentação animal. Nesse contexto, o presente trabalho objetivou avaliar a eficiência de retenção/remoção de fósforo total e nitrogênio total Kjeldahl (NTK) presentes em águas residuárias a partir de dois leitos de fluxo subsuperficial horizontal cultivados com Eichhornia crassipes, com diferença de 43 dias de cultivo entre eles, fixados a um meio suporte. As concentrações de fósforo total variaram de 4,5 a 5,1 mg.L-1 no afluente e de 3,2 a 4,4 mg.L-1 no efluente dos leitos cultivados, enquanto as concentrações de NTK variaram de 95,9 a 104,7 mg.L-1 no afluente e de 77,5 a 85,3 mg.L-1 no efluente.

ABSTRACT Improper disposal, even after treatment, of wastewater can cause negative impacts on receiving water bodies. Particularly, substances such as nitrogen and phosphorus can become, depending on their concentrations, toxic to aquatic organisms or produce favorable conditions for the proliferation of a vegetation that can start the process of eutrophication. Constructed wetlands are a wastewater treatment built to mimic the structure of natural wetlands, promoting mechanisms of phytoremediation. Despite E. crassipes be an invasive plant which causes problems in eutrophic lakes and rivers, its use may be interesting in wetlands because it is an ornamental plant, which will increase wastewater treatment system's acceptance, and it can be reused in crafts, in biofuel production and in animal feed. In this context, the present study aimed to evaluate the efficiency of the retention/removal of total phosphorus and Kjeldahl nitrogen (TKN) present in wastewater by two subsurface horizontal flow constructed wetland system cultivated with Eichhornia crassipes, with a difference of 43 days of cultivation, fixed to a support medium. The concentrations of total phosphorus ranged from 4.5 to 5.1 mg.L-1 in the affluent and from 3.2 to 4.4 mg.L-1 in the effluent of constructed wetlands, whereas NTK concentrations ranged from 95.9 to 104.7 mg.L-1 in the effluent, and from 77.5 to 85.3 mg.L-1 in the effluent.

Establishment of National Reference Standards of Sulfadimidine Impurities / 中国药学杂志

OBJECTIVE: To establish the national reference standards of sulfadimidine impurities thus to provide guarantee for improving the standard of quality control of sulfadiazine in China. METHODS: First, the structures of sulfadimidine impurities A and E were validated by infrared spectrocopy, mass spectrum and nuclear magnetic resonance method. Then, the purities of impurities A and E were determined using the method of related substance test for sulphadiazine in the European Pharmacopoeia (version 9.0),their water content and residue on ignition were determined as well. The contents of sulfadimidine impurities A and E were determined by using mass balance method. Meanwhile, external standard method and nuclear magnetic quantitative method were used to calculate the content, which were mutually verified with the mass balance method. Finally, the correction factors of sulfadiazine impurities A and E at 241 nm were determined using standard curve method. RESULTS: The structures of sulfadimidine impurities A and E were confirmed, and the contents of impurities A and E were 99.1% and 98.7%, respectively, which were calculated by mass balance method. The results were consistent with those obtained from external standard method and nuclear magnetic quantification method. The correction factors of impurities A and E to sulfadimidine were 0.97 and 0.63, respectively. CONCLUSION: The first batch of national standard substances of sulfadimidine impurities A and E were established successfully.

Assessment of the Purity of Emodin by Quantitative Nuclear Magnetic Resonance Spectroscopy and Mass Balance

Quantitative nuclear magnetic resonance (qNMR) is a well-established method adopted by international pharmacopoeia for quantitative and purity analyses. Emodin is a type of anthraquinone, well known as the main active component of Fabaceae, Polygonaceae and Rhamnaceae. Purity analysis of emodin is usually performed by using the high-performance liquid chromatography (HPLC)-UV method. However, it cannot detect impurities such as salts, volatile matter, and trace elements. Using the qNMR method, it is possible to determine the compound content as well as the nature of the impurities. Several experimental parameters were optimized for the quantification, such as relaxation delay, spectral width, number of scans, temperature, pulse width, and acquisition time. The method was validated, and the results of the qNMR method were compared with those obtained by the HPLC and mass balance analysis methods. The qNMR method is specific, rapid, simple, and therefore, a valuable and reliable method for the purity analysis of emodin.

Nitrogen and phosphorus flux from the production of Nile tilapia through the application of environmental indicators / Fluxo de nitrogênio e fósforo na produção de tilápia-do-nilo (Oreochromis niloticus) a partir da aplicação de indicadores ambientais

Abstract We aimed in this study utilize environmental indicators as a quantitative method to evaluate and discuss the nitrogen (TN) and phosphorus (TP) flux by a production stage grow-out (termination) of Nile tilapia (Oreochromis niloticus) in fishpond. The TN and TP load, the mass balance, the input of TN and TP via feed and the converted nutrients in fish biomass are the environmental indicators applied in this study. During the production cycle (128 days), the system exported 15,931 g TN and 4,189 g TP that were related to the amount of feed supplied (r Pearson = 0.8825 and r = 0.8523, respectively), corroborated by the feed conversion ratio (1.61:1). The indicators showed that 26% TN and 45% TP were reversed into fish biomass, 62% TN and 40% TP were retained in the fishpond, and 12% TN and 15% TP were exported via effluent. The largest contribution of nutrients generated by the system and exported via effluent was observed in phase III and IV. This result is supported by the feed conversion ratio 2.14 and 2.21:1 obtained at this phase, a fact explained by the amount of feed offered and the fish metabolism. Application of environmental indicators showed to be an efficient tool to quantify flux of TN and TP produced during the grow-out period of Nile tilapia and therefore, guide management practices more sustainable. Concerning the environmental sustainability of the activity the implementation of best management practices such as the better control of the feed amount offered would lead to a smaller loss of TN and TP to the water. Furthermore, the use of better quality feeds would allow greater nutrient assimilation efficiency.

Resumo Nós objetivamos neste estudo, utilizar indicadores ambientais como método quantitativo para avaliar e discutir sobre o fluxo de nitrogênio (TN) e fósforo (TP) na etapa final de crescimento (terminação) de tilápia-do-nilo (Oreochromis niloticus) em viveiro escavado. A carga de TN e TP, o balanço de massa, a entrada de nutrientes via ração e o TN e TP convertido em biomassa de peixe foram os indicadores ambientais utilizados neste estudo. Durante o ciclo produtivo (128 dias), o sistema exportou 15.931 g NT e 4.189 g PT os quais foram relacionadas às quantidades de alimento fornecido (r Pearson = 0,8825 e r = 0,8523, respectivamente), corroborada pela conversão alimentar (1,61:1). Os indicadores evidenciaram que 26% NT e 45% PT foram revertidos em biomassa de peixe, 62% NT e 40% PT ficaram retidos no viveiro e 12% NT e 15% PT foram exportados via efluente. O maior aporte de nutrientes gerado pelo sistema e exportado via efluente foi verificado nas fases III e IV. Este resultado é corroborado pelas taxas de conversão alimentar de 2,14 e 2,21:1 obtida nestas fases, fato explicado pela quantidade de ração ofertada e pelo metabolismo dos peixes. A aplicação dos indicadores ambientais mostrou ser uma ferramenta eficiente para quantificar o fluxo de TN e TP produzidos durante a etapa final de crescimento de tilápia-do-nilo e com isso orientar práticas de manejo mais sustentáveis. Com vistas à sustentabilidade ambiental da atividade, a implantação de boas práticas de manejo tais como o melhor controle da quantidade de alimento ofertado levaria a menor perda de NT e PT para a água. Além disso, o uso de rações de melhor qualidade permitiria maior eficiência de assimilação desses nutrientes.

Nitrogen and phosphorus flux from the production of Nile tilapia through the application of environmental indicators

Abstract We aimed in this study utilize environmental indicators as a quantitative method to evaluate and discuss the nitrogen (TN) and phosphorus (TP) flux by a production stage grow-out (termination) of Nile tilapia (Oreochromis niloticus) in fishpond. The TN and TP load, the mass balance, the input of TN and TP via feed and the converted nutrients in fish biomass are the environmental indicators applied in this study. During the production cycle (128 days), the system exported 15,931 g TN and 4,189 g TP that were related to the amount of feed supplied (r Pearson = 0.8825 and r = 0.8523, respectively), corroborated by the feed conversion ratio (1.61:1). The indicators showed that 26% TN and 45% TP were reversed into fish biomass, 62% TN and 40% TP were retained in the fishpond, and 12% TN and 15% TP were exported via effluent. The largest contribution of nutrients generated by the system and exported via effluent was observed in phase III and IV. This result is supported by the feed conversion ratio 2.14 and 2.21:1 obtained at this phase, a fact explained by the amount of feed offered and the fish metabolism. Application of environmental indicators showed to be an efficient tool to quantify flux of TN and TP produced during the grow-out period of Nile tilapia and therefore, guide management practices more sustainable. Concerning the environmental sustainability of the activity the implementation of best management practices such as the better control of the feed amount offered would lead to a smaller loss of TN and TP to the water. Furthermore, the use of better quality feeds would allow greater nutrient assimilation efficiency.

Resumo Nós objetivamos neste estudo, utilizar indicadores ambientais como método quantitativo para avaliar e discutir sobre o fluxo de nitrogênio (TN) e fósforo (TP) na etapa final de crescimento (terminação) de tilápia-do-nilo (Oreochromis niloticus) em viveiro escavado. A carga de TN e TP, o balanço de massa, a entrada de nutrientes via ração e o TN e TP convertido em biomassa de peixe foram os indicadores ambientais utilizados neste estudo. Durante o ciclo produtivo (128 dias), o sistema exportou 15.931 g NT e 4.189 g PT os quais foram relacionadas às quantidades de alimento fornecido (r Pearson = 0,8825 e r = 0,8523, respectivamente), corroborada pela conversão alimentar (1,61:1). Os indicadores evidenciaram que 26% NT e 45% PT foram revertidos em biomassa de peixe, 62% NT e 40% PT ficaram retidos no viveiro e 12% NT e 15% PT foram exportados via efluente. O maior aporte de nutrientes gerado pelo sistema e exportado via efluente foi verificado nas fases III e IV. Este resultado é corroborado pelas taxas de conversão alimentar de 2,14 e 2,21:1 obtida nestas fases, fato explicado pela quantidade de ração ofertada e pelo metabolismo dos peixes. A aplicação dos indicadores ambientais mostrou ser uma ferramenta eficiente para quantificar o fluxo de TN e TP produzidos durante a etapa final de crescimento de tilápia-do-nilo e com isso orientar práticas de manejo mais sustentáveis. Com vistas à sustentabilidade ambiental da atividade, a implantação de boas práticas de manejo tais como o melhor controle da quantidade de alimento ofertado levaria a menor perda de NT e PT para a água. Além disso, o uso de rações de melhor qualidade permitiria maior eficiência de assimilação desses nutrientes.

Environmental indicators in effluent assessment of rainbow trout (Oncorhynchus mykiss) reared in raceway system through phosphorus and nitrogen / Indicadores ambientais na avaliação de efluentes de truta arco-íris (Oncorhynchus mykiss) criados em sistema de raceway através do fósforo e nitrogênio

Abstract The phosphorus and nitrogen discharge via effluent of intensive trout farming system was quantified through the use of environmental indicators. The nutrient loads, the mass balance, the estimated amount of nutrients in feed and the amount of nutrients converted in fish biomass were calculated based on the concentrations of phosphorus (P) and nitrogen (N) in the feed and in the water. Of the offered feed, 24.75 kg were available as P and 99.00 kg as N, of these, 9.32 kg P (38%) and 29.12 kg N (25%) were converted into fish biomass and 15.43 kg P (62%) and 69.88 kg N (75%) were exported via effluent. The loads and the mass balance show the excessive discharge of nutrients via effluent, corroborated by the feed conversion ratio (2.12:1) due to the low efficiency of feed utilization, therefore, it is proposed the use of this zootechnical parameter as environmental indicator. In addition, feed management practices are not adequate, highlighting the low frequency of feeding during the day, excessive amount and low quality of feed offered. These results demonstrate the need for adequate feed management and the need for careful monitoring of effluent.

Resumo A descarga de fósforo e nitrogênio via efluente do sistema intensivo de truticultura foi quantificada através da utilização de indicadores ambientais. As cargas de nutrientes, o balanço de massa, a quantidade estimada de nutrientes na ração e a quantidade de nutrientes convertidos em biomassa de peixes foram calculados com base nas concentrações de fósforo (P) e nitrogênio (N) na ração e na água. Da ração oferecida, 24,75 kg estavam disponíveis como P e 99,00 kg como N, destes, 9,32 kg de P (38%) e 29,12 kg de N (25%) foram convertidos em biomassa de peixe e 15,43 kg P (62%) e 69,88 kg N (75%) foram exportados via efluente. As cargas e o balanço de massa mostram a descarga excessiva de nutrientes via efluente, corroborado pela taxa de conversão alimentar (2,12:1), devido à baixa eficiência na utilização da ração, portanto, propõe-se a utilização deste parâmetro zootécnico como indicador ambiental. Além disso, as práticas de manejo alimentar não são adequadas, destacando a baixa frequência de alimentação durante o dia, quantidade excessiva e baixa qualidade da alimentação ofertada. Esses resultados demonstram a necessidade de manejo alimentar adequado e de monitoramento do efluente.

Resíduos de construção e demolição: avaliação de métodos de quantificação / Construction and demolition waste: evaluation of quantification methods

Neste trabalho, estimou-se a gerão dos resíduos de construção e demolição por dois métodos de quantificação, um indireto e outro direto, considerando-se a produção advinda dos agentes informais e formais. O método indireto considerou a área construída das edificações (construção) e transformação dos pontos de ligação de água e luz instalados (reforma). O método direto identificou a geração advinda de agentes informais e formais nos pontos de disposição finais em diferentes regiões do município, empregando-se o conceito de balanço de massa. Não é possível quantificar a geração de resíduos de construção e demolição dos agentes informais (reformas) por meio de dados indiretos relacionados Às transformações dos pontos de água no município. Há indícios de que as transformações dos pontos de energia elétrica sejam um indicador indireto mais preciso, podendo evitar a dispendiosa quantificação direta.

In this paper, construction and demolition waste generation was estimated by two quantification methods, one direct and other indirect, regarding informal and formal generators. Construction area and transformation of the points of water and energy were applied for indirect quantification method. For the direct one, volume of dumping areas associated with informal and formal generators in different regions of municipality were quantified and the mass balance was applied. Indirect quantification of informal generators by transformation points of water is not precise. There are evidences that transformation points of energy can be more precise, avoiding costly direct construction and demolition waste quantification method.

Assesment of soil erosion by 137Cs technique in native forests in Londrina City, Parana, Brazil

The aim of this work was to assess the soil erosion process in native forest by the 137Cs methodology. The mass balance model was applied to assess the rates of soil loss in three native forests around of Londrina city, Paraná, Brazil. 137Cs distribution depth was of exponential type for the three forests and 137Cs inventory was 241 Bq m-2 for Mata 1, 338 Bq m-2 for Mata 2 and 325 Bq m-2 for Mata UEL. The soil loss value calculated for three native forests was: 6,684 kg ha-1 yr-1 for Mata 1, 1,788 kg ha-1 yr-1 for Mata 2 and 4,524 kg ha-1 yr-1 for Mata UEL.

O processo de erosão de solo em floresta nativa tem sido pouco investigado. Como a metodologia do césio-137 dá resultados tanto de taxas de erosão de solo como a bioturbação no perfil de solo, ele tem sido usado para avaliar o processo de erosão de solo nestes ecossistemas. O modelo de balanço de massa foi aplicado para avaliar as taxas de perdas de solo em três florestas nativas na região de Londrina, Paraná, Brasil. A distribuição em profundidade do césio-137 para as três florestas é do tipo exponencial. O inventário de césio-137 foi de 241 Bq m-2 para Mata 1, 338 Bq m-2 para Mata 2 e 325 Bq m-2 para Mata UEL.O valor de perda de solo calculado para Mata 1 foi 6,684 kg ha-1 yr-1, 1,788 kg ha-1 yr-1 para Mata 2 e 4,524 kg ha-1 yr-1 para Mata UEL.

Comparison of Fluid Kinetic Model of Normal Saline with Hartmann's Solution in Adult Volunteers

BACKGROUND: Changes in the volume of fluid space expanded by intravenous infusion of crystalloid solution have been analyzed using mathematical models. Crystalloids with similar osmolality would reveal no significant differences in distribution and elimination from the body. But each solution has different ionic composition, this can affect fluid volume kinetics. Therefore, we evaluated the fluid volume kinetics of normal saline and Hartmann's solution. METHODS: After infusion of 15 ml/kg of normal saline (n=5) and Hartmann's solution (n = 4) over 30 min and measured a serial hemoglobin concentration. The changes were expressed as fractional dilution and then plotted against time. The curves were fitted to two-volume model using non linear least square fitting process. RESULTS: Central and peripheral volume space were present. There were no significant differences between the two groups on central volume, peripheral volume and expansion ratio of fluid space per body weight and expansion ratio of peripheral volume. The expansion ratio of central volume was greater in Hartmann's solution than normal saline from 25 min to 60 min after infusion. Hartmann's solution expanded fluid space higher than normal saline on initial period. CONCLUSIONS: There were no significant differences in fluid kinetic parameters between normal saline and Hartmann's solution. However, the volume expansion effect of Hartmann's solution was more rapid than normal saline in early infusion period.