HPLC法测定硝呋太尔的4种中间体的含量和有关物质

目的建立硝呋太尔合成过程中4种中间体2-(甲硫基甲基)-氧杂环丙烷(MMOP),3-甲硫基-2-羟基-丙基肼(HMPL),N-氨基-5-甲硫基甲基-2-噁唑烷酮(AMOD)和5-硝基糠醛(5-NFA)的HPLC分析方法。方法 MMOP和5-NFA以70 mmol.L-1磷酸氢二钠溶液-甲醇(85∶15)为流动相,HMPL和AMOD以70 mmol.L-1磷酸氢二钠溶液-乙腈(97∶3)为流动相,MMOP、HMPL和5-NFA以Agilent ZORBAX SB-Phenyl柱(250 mm×4.6 mm,5μm)分析,AMOD以Agilent Eclipse XDB-C8柱(150mm×4.6 mm,5μm)测定,检测波长分别为210,205,205和312 nm。结果 MMOP、HMPL、AMOD和5-NFA分别在7.4~266.4,26.0~2 600,38.0~3 800和18.5~1 850μg.mL-1范围内,峰面积与质量浓度呈良好的线性关系,平均回收率分别为99.9%,99.8%,100.1%和100.1%。4种中间体在酸、碱、氧化、直火和光照条件下的破坏实验时主成分峰与各降解产物及有关物质峰均能很好地分离。结论该方法简单、准确、重复性好,可用于硝呋太尔4种中间体的质量控制。

Determination of the contents and 4 kinds of intermediates of nifuratel by HPLC

Objective To establish HPLC methods for the four intermediates of nifuratel including 2-methylthiomethyl-oxacyclopropane （ MMOP）, 1-hydrazino-3-（ methylthio ） propan-2-ol （ HMPL）, 3-amino-5-methylthiomethyl-2-oxazolidinone （AMOD） and 5- nitrofurfural （5-NFA）. Methods The separation of MMOP and 5-NFA were performed on an Agilent ZORBAX SB-Phenyl column （250 mm× 4. 6 mm,5 μm） with 70 mmol ·L^-1 disodium monohydrogen phosphate-methanol （85 ： 15）as the mobile phase. AMOD was performed on an Agilent Eclipse XDB-C8 column （150 mm × 4. 6 mm, 5 μm） with 70 mmol · L^-1 disodium monohydrogen phosphate-acetonitrile （97 ： 3） as the mobile phase, while HMPL was determined on an Agilent ZORBAX SB-Phenyl column （250 mm×4. 6 mm,5 μm} with 70 mmol · L^-1 disodium monohydrogen phosphate-acetonitrile （97 ： 3） as the mobile phase. The detection wavelength of MMOP, HMPL, AMOD and 5-NFA were set at 210,205,205 and 312 nm, respectively. Results There were a good linear relationships between peaks area and concentration of four components, and the calibration curves of peak area and concentration were linearity in the ranges of 7.4-266.4 μg· mL^-1 for MMOP, 26.0-2 600μg · mL^-1 for HMPL, 38.0- 3 800μg ~ mL^-1 for AMOD,and 18.5-1 850μg · mL^-1 for 5-NFA. The average recoveries were 99.9% ,99.80%,100. 1% and 100.1%, respectively. The principal component peak with the degradation products and related substances peaks of the four intermediates were all well separated in the acid, alkali, oxidation, direct fire and light degradation texts. Conclusions The established method was simple,and accurate and can be used for the quality control of the four intermediates of nifuratel.