摘要
目的合成异烟肼的活性衍生物N'-十二烷酰异烟肼并对其进行处方前研究,为注射用N'-十二烷酰异烟肼温敏凝胶的处方设计提供基础。方法采用~1H-NMR、LC-MS、UV和HPLC对合成的N'-十二烷酰异烟肼进行确证和纯度测定。并用HPLC法测定N'-十二烷酰异烟肼的油水分配系数、在不同溶剂中的平衡溶解度、稳定性等理化性质。结果所得的N'-十二烷酰异烟肼纯度大于99%,~1H-NMR、LC-MS、UV确证其结构正确。N'-十二烷酰异烟肼溶液在高温(60℃)和强光(4500 Lx)条件下稳定,Log P为3.48,难溶于水,在相应的溶出介质中满足漏槽条件。结论建立的分析方法准确可靠,处方前研究表明N'-十二烷酰异烟肼原料药较稳定。
Objective To synthesize the active derivative of isoniazid, N＇-dodecanoylisoniazid and conduct preprescription study, and to provide reference for the formulation design of thermosensitive injectable hydrogel of N＇-dodecanoylisoniazid. Methods The structure and purity of the synthesized N＇-dodecanoylisoniazide were characterized by ~1H-NMR, LC-MS, UV and HPLC. The oil-water partition coefficient, the equilibrium solubility, stability and other physicochemical properties in different solvents of N＇-dodecanoylisoniazid were determined by HPLC. Results N＇-dodecanoylisoniazide with a purity of over 99% was successfully synthesized. The results of ~1H-NMR and LC-MS were in good agreement with the theoretical results. N＇-dodecanoylisoniazid was stable at 60 ℃ and under strong light（4500 Lx）, and the Log P was 3.48. It was for N＇-dodecanoylisoniazid difficult to dissolve in water and the sink condition of N＇-dodecanoylisoniazid could be achieved in other dissolution media. Conclusion The established HPLC method for determining the drug content and related substances of N＇-dodecanoylisoniazid is accurate and reliable. The preformulation study shows that N＇-dodecanoylisoniazid is stable.
作者
何青
郭彬彬
尹耀庭
丁劲松
HE Qing GUO Bin-bin YIN Yao-ting DING Jln-song(Hunan Institute for Tuberculosis Control, Changsha 410013 School of Pharmaceutical Sciences, Central South University, Changsha 410013)
出处
《中南药学》
CAS
2017年第9期1201-1205,共5页
Central South Pharmacy
基金
省科委基金项目(课题编号:2014FJ3037)
