This approach was developed to achieve an accurate, fast, economic and sensitivity to estimation of diphenhydramine Hydrochloride. The dye that produced via reaction between diphenhydramine HCl with thymol blue in acidic medium pH ≈ 4.0. The ion pair method include an optimization study to formed yellowcolored that extraction by liquid – liquid method. The product separated of complexes by using by chloroform solution measured spectrophotometry at 400 nm. The analysis data at optimum conditions showed that linearity concentration in a range of calibration curve 1.0 – 50 μg /mL, limit of detectionand limit of quantification 0.0786 and 0.2358 μg/mL respectively. The molar absorptivity and Sandell’s sensitivity were 1.8 × 10 -4 L/mol. cm and 0.0399 μg/cm 2 respectively. The developed procedure was successfully applied for the diphenhydramine HCl determination in their pure form and in pharmaceuticals preparation with not interference of additives.
