Shehzadi Naureen, Hussain Khalid, Islam Muhammad, Bukhari Nadeem Irfan, Asif Noman, Khan Muhammad Tanveer, Salman Muhammad, Qamar Shaista, Parveen Sajida, Zahid Fakhra, Shah Arshad Ali, Bilal Abida, Abbasi Muhammad Athar, Siddiqui Sabahat Zahra, Rehman Azizur
Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan / Faculty of Pharmacy, the University of Lahore, Lahore, Pakistan.
Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan.
Pak J Pharm Sci. 2018 Mar;31(2(Suppl.)):603-609.
The present study describes the development and validation of a simple high performance liquid chromatographic method for the determination of a novel drug candidate, 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol. The stability-indicating capacity of the method was evaluated by subjecting the compound's solution to hydrolytic, oxidative, photolytic, transition metal- and thermal- stress. The chromatographic separation was achieved over a C18 column (Promosil, 5 µm, 4.60 × 250 mm), maintained at 25°C, using an isocratic mobile phase comprising a mixture of acetonitrile and acidified water of pH 2.67 (1:1, v/v), at a flow rate of 1.00 mL/min and detection using a fluorescent light detector (excitation at 250 nm and emission at 410 nm). The Beer's law was followed over the concentration range 2.50-50.00 μg/ml. The recovery (98.56-100.19%, SD <5%), intraday accuracy and precision (97.31-100.81%, RSD <5%), inter-day accuracy and precision (97.50-100.75%, RSD <5%) and intermediate accuracy and precision (98.10-99.91%, RSD <5%) indicated that the method was reliable, repeatable, reproducible and rugged. The resolution and selectivity factors of the compound's peak from the nearest resolving peak, particularly in case of dry heat and copper metal stress, were found to be greater than 2 and 1, respectively, which indicated specificity and selectivity. The compound was extensively decomposed in alkaline-hydrolytic, oxidative, metal- and dry heat- stress. However, the compound in acidic and neutral conditions was resistant to photolysis. The results of the present study indicate that the developed method is specific, selective, sensitive and suitable, hence, may be used for quality control, stability testing and preformulation studies.
本研究描述了一种用于测定新型候选药物5-[(4-氯苯氧基)甲基]-1,3,4-恶二唑-2-硫醇的简单高效液相色谱法的开发与验证。通过使该化合物的溶液经受水解、氧化、光解、过渡金属和热应激来评估该方法的稳定性指示能力。色谱分离在C18柱（Promosil，5 µm，4.60×250 mm）上进行，柱温保持在25°C，使用由乙腈和pH 2.67的酸化水（1:1，v/v）组成的等度流动相，流速为1.00 mL/min，并使用荧光检测器进行检测（激发波长为250 nm，发射波长为410 nm）。在2.50 - 50.00 μg/ml的浓度范围内符合比尔定律。回收率（98.56 - 100.19%，标准差<5%）、日内准确度和精密度（97.31 - 100.81%，相对标准偏差<5%）、日间准确度和精密度（97.50 - 100.75%，相对标准偏差<5%）以及中间精密度（98.10 - 99.91%，相对标准偏差<5%）表明该方法可靠、可重复、可重现且耐用。该化合物峰与最近的分离峰之间的分离度和选择性因子，特别是在干热和铜金属应激情况下，分别大于2和1，这表明了特异性和选择性。该化合物在碱性水解、氧化、金属和干热应激下大量分解。然而，该化合物在酸性和中性条件下对光解具有抗性。本研究结果表明，所开发的方法具有特异性、选择性、灵敏性且适用，因此可用于质量控制、稳定性测试和制剂前研究。
