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标题：Reverse-phase chromatographic determination and intrinsic stability behavior of 5-[(4-chlorophenoxy)methyl]- -1,3,4-oxadiazole-2-thiol
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作者：NAUREEN SHEHZADI ; NAUREEN SHEHZADI ; KHALID HUSSAIN 等
期刊名称：Acta Pharmaceutica
电子版ISSN：1846-9558
出版年度：2018
卷号：68
期号：4
页码：409-424
DOI：10.2478/acph-2018-0036
语种：English
出版社：Sciendo
摘要：The study describes the development and preliminary validation of a simple reverse-phase chromatographic method for determination of a novel drug candidate,5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM),in bulk and stressed solution,in order to find out the intrinsic stability behavior of the compound.Isocratic elution was carried out at a flow rate of 1.0 mL min–1 through a Promosil C18 column maintained at 25 °C,using the mobile phase comprising acetonitrile and aqueous o-H3PO4 (pH 2.67) (1:1,V/V).Detection was performed at 258 nm.The response of the detector was linear in a concentration range of 1.25–50.00 µg mL–1 with the correlation coefficient of 0.9996 ± 0.0001.Cumulative intra-day,inter-day and inter-instrument accuracy (99.5 ± 1.0,100.2 ± 1.0 and 100.3 ± 0.4 %,resp.) with RSD less than 5 % indicated that the method was accurate and precise.The resolution and selectivity factor (>2 and >1,resp.),particularly in copper metal- and dry-heat-stress solutions,depicted the selectivity of the method.OXCPM remained stable under hydrolytic (acidic and neutral pH,≤ 37 °C),photolytic and moist heat stress conditions.Under alkaline conditions (hydrolytic and photolytic),polar products were formed that eluted very fast through the column (tR < 3.75 min).At room temperature,the compound was susceptible to oxidation by hydrogen peroxide and transition metals.The ionogram of most of the stress solutions indicated the presence of a product having m/z 256,which might be a result of N- or Smethylation or -SH oxidation.The results of the study indicate that the method is selective,sensitive and suitable to be used for determination of OXCPM in bulk and under stress conditions.
关键词：5-[(4-chlorophenoxy)methyl]-1;3;4-oxadiazole- -2-thiol;forced degradation;stability;RP-HPLC/DAD