The present investigation is based on an in vitro incompatibility study between valsartan and hydrochlorothiazide by spectroscopic and reverse-phase high-pressure liquid chromatography (RP-HPLC) methods. The method has been developed and validated by ultraviolet (UV) spectroscopic method using methanol and water (1:4) as the solvent. The RP-HPLC study has been carried out using acetonitrile, methanol and 50 Mm phosphate buffer (20:50:30 %) adjusted to pH 3 with orthophosphoric acid. The methods show linearity at the concentration range of 1-5 μg/ml with correlation coefficient 0.9994 for valsartan and 0.9978 for hydrochlorothiazide in the concentration range of 1-5 μg/ml. Both the methods have shown a percentage relative standard deviation values less than 2. The in vitro incompatibility study has been carried out by UV-spectroscopic and RP-HPLC methods. The results of the study show that there is a change in the concentration level of both drugs in combination. The structure of the interacting compound has been determined by spectral analysis using IR, ¹H NMR and LC-MS study. The spectral analysis confirms the formation of the new complex between valsartan and hydrochlorothiazide. The results obtained from the LC-MS study also correlate the reason behind an increase in the concentration of valsartan and decreases the concentration of hydrochlorothiazide during recovery study by spectroscopic and RP-HPLC method.

中文翻译：

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光谱和RP-HPLC法研究缬沙坦与氢氯噻嗪的体外不相容性

本研究基于缬沙坦与氢氯噻嗪在光谱和反相高压液相色谱（RP-HPLC）方法之间的体外不相容性研究。该方法已经开发并通过使用甲醇和水（1：4）作为溶剂的紫外（UV）光谱法进行了验证。RP-HPLC研究使用乙腈，甲醇和50 Mm磷酸盐缓冲液（20:50:30％）（用正磷酸调节至pH 3）进行。该方法在1-5μg/ ml的浓度范围内表现出线性，在1-5μg/ ml的浓度范围内，缬沙坦的相关系数为0.9994，氢氯噻嗪的相关系数为0.9978。这两种方法都表现出了百分比相对标准偏差值小于2。体外已经通过紫外光谱和RP-HPLC方法进行了不相容性研究。研究结果表明，两种药物合用的浓度水平都有变化。相互作用的化合物的结构已通过使用IR，¹ H NMR和LC-MS研究的光谱分析确定。光谱分析证实了缬沙坦和氢氯噻嗪之间新的络合物的形成。LC-MS研究获得的结果还与通过光谱和RP-HPLC方法进行回收研究期间缬沙坦浓度增加和氢氯噻嗪浓度降低的原因相关。