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早期研发抗生素品种的纯度与效价之间的定量关系尚不明确,同时控制HPLC纯度和微生物效价是目前各国药典的共同质控策略。由于效价属于特定计量单位,其量值无法直接溯源至国际单位(SI),因此探讨抗生素效价与纯度间的定量关系,实现利用HPLC法同时测定抗生素的纯度与效价成为当前抗生素质量控制的热点。本研究选择多组分抗生素庆大霉素,通过分别制备庆大霉素C1a、C2、C2a和C1单组分样品,利用NMR、HPLC和微生物检定法确定每个C组分的有效成分纯度与理论效价之间的定量关系:每1 mg庆大霉素C1a纯品相当于1 286.98庆大霉素效价单位;每1 mg庆大霉素C2纯品相当于1 095.74庆大霉素效价单位;每1 mg庆大霉素C2a纯品相当于1 079.52庆大霉素效价单位;每1 mg庆大霉素C1纯品相当于739.61庆大霉素效价单位。进而建立了根据HPLC分析得到的庆大霉素C组分的比例与含量确定庆大霉素效价的方法,实现了庆大霉素HPLC纯度分析与效价测定的统一。此外,证明了在蒸发光散射检测器中庆大霉素诸组分与小诺霉素的响应因子一致,即不需要制备庆大霉素诸组分标准品,仅通过小诺霉素标准品就能准确定量诸庆大霉素组分,为HPLC定量庆大霉素诸组分提供了方便。上述方法有望作为常规的质量控制方法,简化目前药典中的繁琐质控策略。
The quantitative relationship between purity and potency of the early development of antibiotic varieties is not yet clear. At the same time, the control of HPLC purity and microbial potency is the common control strategy of pharmacopoeia in various countries. Because the titer belongs to a specific unit of measurement, its value can not be directly traced back to the International Unit (SI), therefore, the quantitative relationship between the potency and purity of the antibiotic is explored, and the purity and titer of the antibiotic simultaneously determined by the HPLC method become the current quality control of antibiotics Hot spots. In this study, the multi-component antibiotic gentamicin was selected. The monocomponent gentamicins C1a, C2, C2a and C1 were prepared respectively, and the purity of active ingredients of each component C was determined by NMR, HPLC and microbiological assay Quantitative relationship between the theoretical potency: 1 mg gentamycin per 1 mg of pure equivalent of 1 286.98 gentamicin potency units; 1 mg of gentamicin C2 pure equivalent of 1 095.74 gentamicin Unit of price; each 1 mg gentamycin C2a pure equivalent of 1 079.52 gentamicin potency units; each 1 mg gentamicin C1 pure product equivalent to 739.61 gentamicin potency units. Then the method of determining the gentamycin potency according to the ratio and content of gentamicin C component obtained by HPLC was established and the unification of gentamicin HPLC purity analysis and potency determination was achieved. In addition, it has been demonstrated that the response factors of gentamicin components to minocycline in the evaporative light scattering detector are consistent, ie no gentamicin compositional standards need to be prepared, only the minocycline standard Gentamicin components can be accurately quantitated to facilitate the quantitation of gentamicin components by HPLC. The above method is expected to be used as a routine quality control method to simplify cumbersome quality control strategies in current Pharmacopoeia.