The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates...The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.展开更多
Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic me...Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.展开更多
Objective To evaluate the antimutagenicity of propolis in vivo and in vitro. Methods Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect muta...Objective To evaluate the antimutagenicity of propolis in vivo and in vitro. Methods Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice testicle cell were applied as a test model in vivo against two mutagens CP and MMC. Results The present study clearly demonstrated that propolis could inhibit mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and significant antimutagenic effects (P<0.05) were obtained in TA98 strain at 2000 and 3000 mg/plate. It also could inhibit mutagenicity of both DMC and 2AF to TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P<0.05) appeared at 1000, 2000, and 3000 mg/plate. The results of antimutagenicity test in vivo revealed that propolis could inhibit MN formation significantly (P<0.05) at the doses of 45.0 and 135.0 mg/kg b. w., and decrease the frequency of chromosome aberrants and chromosome aberrant cells significantly (P<0.05) only at the dose of 135.0 mg/kg b. w. Conclusion The propolis is a good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC in vivo.展开更多
Mesocyclops leukarti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a stud...Mesocyclops leukarti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a study of removal effect on Mesocylops leukarti with chlorine dioxide in a waterworks was performed. The results showed that Mesocyclops leukarti could be effectively removed from water by 1.0 mg/L chlorine dioxide prcoxidation combined with the conventional drinking water treatment process. Higher oxidizability and molecular state of chlorine dioxide in water is the key to the inactivation of Mesocyclops leukarti. The chlorite, disinfection by-products （DBPs） of chlorine dioxide, was stable at 0.45 mg/L, which is lower than that critical value of the USEPA. GC-MS examination showed that the quantity of organic substance in the water treated by chlorine dioxide obviously decreased. Ames test further revealed that the mutagenicity was reduced by chlorine dioxide with respect to prechlorine. The propagation ofMesocyclops leukorti can be inactivated effectively and safely by chlorine dioxide pre-oxidation.展开更多
The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experim...The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.展开更多
文摘The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
文摘Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.
文摘Objective To evaluate the antimutagenicity of propolis in vivo and in vitro. Methods Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice testicle cell were applied as a test model in vivo against two mutagens CP and MMC. Results The present study clearly demonstrated that propolis could inhibit mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and significant antimutagenic effects (P<0.05) were obtained in TA98 strain at 2000 and 3000 mg/plate. It also could inhibit mutagenicity of both DMC and 2AF to TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P<0.05) appeared at 1000, 2000, and 3000 mg/plate. The results of antimutagenicity test in vivo revealed that propolis could inhibit MN formation significantly (P<0.05) at the doses of 45.0 and 135.0 mg/kg b. w., and decrease the frequency of chromosome aberrants and chromosome aberrant cells significantly (P<0.05) only at the dose of 135.0 mg/kg b. w. Conclusion The propolis is a good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC in vivo.
基金The Hi-Tech Research and Development Program (863) of China (No. 2003AA601120)
文摘Mesocyclops leukarti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a study of removal effect on Mesocylops leukarti with chlorine dioxide in a waterworks was performed. The results showed that Mesocyclops leukarti could be effectively removed from water by 1.0 mg/L chlorine dioxide prcoxidation combined with the conventional drinking water treatment process. Higher oxidizability and molecular state of chlorine dioxide in water is the key to the inactivation of Mesocyclops leukarti. The chlorite, disinfection by-products （DBPs） of chlorine dioxide, was stable at 0.45 mg/L, which is lower than that critical value of the USEPA. GC-MS examination showed that the quantity of organic substance in the water treated by chlorine dioxide obviously decreased. Ames test further revealed that the mutagenicity was reduced by chlorine dioxide with respect to prechlorine. The propagation ofMesocyclops leukorti can be inactivated effectively and safely by chlorine dioxide pre-oxidation.
文摘The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.
