Highly sensitive, simple and accurate reversed phase liquid chromatographic and first derivative spectrophotometric methods were developed for determination of the non-steroidal anti-inflammatory drugnaproxen and the antihistaminic diphenhydramine in their binary mixtures. The HPLC method involves separation of naproxen and diphenhydramine on XBridgeTMC18 reversed phase (4.6×150 mm, particle size 5μm) column using a mobile phase consists of ethanol: phosphate buffer; pH 3in a ratio of 60:40 (v/v). The flow rate was 1 mL.min-1with ultraviolet detection at 216 nm. The calibration graphs are linear from 0.5 to 100 μg.mL-1for naproxen and from 2 to 100 μg.mL-1for diphenhydramine .The mean % recoveries were found to be 100.910±0.358 and 99.863±1.14 for naproxen and diphenhydramine, respectively using this HPLC method. Thespectrophotometric method was based on measuring 1D at 243.8 nm for determination of naproxen and 1D at 230 nm for determination of diphenhydramine. Linearity ranges were found to be 0.5–3 μg.mL-1 and 2.5-25 μg.mL-1 for naproxen and diphenhydramine, respectively. The mean % recoveries were found to be 100.759±1.275 and 101.002±0.755 for naproxen and diphenhydramine, respectively using the proposed first derivative method.The developed methods were successfully applied for the determination of naproxen and diphenhydramine in laboratory prepared mixtures containing all possible excipients present in the tablet dosage form.
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