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.

Long-Term Stability of HBV, HCV, and HIV-1 National Reference Standards for in vitro Diagnostic Medical Devices Intended to Be Used for the Nucleic Acid Amplification Test / 대한수혈학회지

BACKGROUND: National reference standards are essential to the quality assessment and regulatory approval of in vitro diagnostic medical devices. However, the long-term stability of national reference standards has not been comprehensively secured. This study was performed to assessment on the long-term stability of the hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus-1 (HIV-1) national reference standards intended to be used for the nucleic acid amplification test (NAT). METHODS: The viral loads of the MFDS (Korea Ministry of Food and Drug Safety) working standard and recombinant DNA for HBV, HCV, and HIV-1 were measured before and after storage at −70℃ for up to 72 months using Cobas Ampliprep/Cobas Taqman assays (Roche Molecular System, Inc., Branchburg, USA) at defined time points. RESULTS: The viral loads of national reference standards for in vitro diagnostic medical devices of HBV, HCV, and HIV-1 stored at −70℃ for up to 72 months did not differ significantly from the baseline viral load. The changes in viral load of national reference standards of HBV, HCV, and HIV-1 tested after storage at −70℃ for up to 72 months ranged from −0.36 to 0.16 log10 IU/mL and did not exceed 0.5 log10, which is the estimated intra-assay variation of molecular tests. CONCLUSION: The HBV, HCV, and HIV-1 national reference standards for in vitro diagnostic medical devices intended to be used for the NAT were relatively stable after long-term storage at −70℃ for up to 72 months, regardless of the initial titer.

Establishment of national reference standard of fluconazole impurity h / 中国药学杂志

OBJECTIVE: To introduce the procedure of developing reference standards of fluconazole impurities using fluconazole impurity H as an example and reveal a special problem for establishment of national reference standards. METHODS: Firstly, the structure of fluconazole impurity H was validated by infrared, mass spectrum and nuclear magnetic resonance method. Secondly, its purity was determined using the related substances test of fluconazole in European Pharmacopoeia 8.0 (EP8.0) and Chinese Pharmacopeia (2010 version, Volume 2, ChP2010). Then the major impurities determined by the above two HPLC systems were analyzed by LC-MS method. Finally, the content of fluconazole impurity H, its water content and inorganic impurities were determined by quantitative nuclear magnetic resonance (qNMR) method, Karl Fischer titrimetry method and residue on ignition method respectively. RESULTS: The structure of fluconazole impurity H was identical with that in EP 8.0. The contents of water and inorganic impurities were 0.05% and 0.04%, respectively. It was found that fluconazole impurity H would be partially degraded into fluconazole impurity G in water solution, which resulted in the inaccuracy of the related substances test. The content of impurity H was 99.5% by qNMR method. CONCLUSION: Due to the structural characteristics of fluconazole impurity H, the mass balance method, which is the routine method for determination of the content of reference standards, is not suitable for fluconazole impurity H. In the circumstances, qNMR method can be used as a complementary method for the content determination of reference standards.

Establishment and Multicenter Evaluation of a National Reference Panel for Syphilis Antibodies in Korea

BACKGROUND: Establishment of a national reference panel for syphilis antibodies is necessary to evaluate the performance of in-vitro diagnostic tests for syphilis and to verify test quality. This study aimed to establish a national reference panel for syphilis antibodies, to assess the suitability of a panel for non-treponemal and treponemal testing, and to assess the reactivity of the various tests currently in use. METHODS: Treponemal pallidum particle agglutination (TPPA)-positive and -negative fresh frozen plasma samples were obtained. After the fresh frozen plasma was converted to serum by defibrination, the samples were pooled. Two candidate reference standards containing no syphilis antibodies and 10 candidate reference standards containing syphilis antibodies were prepared on the basis of reactivity in the TPPA assay. Candidate reference standards were tested by three laboratories using five non-treponemal tests and four treponemal tests. RESULTS: All three laboratories reported positive non-treponemal test results for the mixed-titer performance panel (MP)/6-MP/12. MP/1, MP/2, and MP/3 were negative for non-treponemal tests. MP/4 and MP/5 were reported either as positive or negative according to the laboratories. All laboratories reported positive TPPA results for MP/3-MP/12 and negative results for MP/1 and MP/2. No significant difference was detected among the treponemal testing results in three laboratories. CONCLUSIONS: We established 12 candidate national reference standards containing various concentrations of syphilis antibodies. A collaborative study using nine tests demonstrated that 12 candidate national reference standards presented consistent results, except a few assays with low sensitivity, and thus could be used as a national reference panel for syphilis antibody testing.

Establishment of the first national reference pertussis vaccine

Quality of RP5 pertussis vaccines for National Reference was tested and its potency was also calibrated in comparison with the International Standard of Pertussis Vaccine. The results showed that the candidate for National reference RP5 pertussis vaccine lot was met to the quality requirements after being freeze dried. The homogenicity in dry weight, residual moisture, potency and stability of its potency make it became as the first National Reference standard pertussis.