Acta Pharm. 68 (2018) 409-424

 

full paper

Original research paper

 

Reverse-phase chromatographic determination and intrinsic stability behavior of 5-[(4-chlorophenoxy)methyl]-1,3,4-oxadiazole-2-thiol

NAUREEN SHEHZADI, KHALID HUSSAIN, MUHAMMAD ISLAM, NADEEM IRFAN BUKHARI, MUHAMMAD TANVEER KHAN, MUHAMMAD SALMAN, SABAHAT ZAHRA SIDDIQUI, AZIZ-UR-REHMAN and MUHAMMAD ATHAR ABBASI

madam_ada1@yahoo.com, naureentanveerkhan@gmail.com

1 Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore-54030, Pakistan

2 Faculty of Pharmacy, University of Lahore, Lahore, Pakistan

3 Department of Chemistry, Government College University, Lahore-54030, Pakistan

Accepted June 21, 2018

Published online August 29, 2018

 

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 min1 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 1.2550.00 g mL1 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 and 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 may be a result of N- or S-methylation 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.

 

Keywords: 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol, forced degradation, stability, RP-HPLC/DAD