Determination Of Promethazine Hydrochloride And Its Preparations By Highly-accurate Nephelometric Titration

Titrimetry is often applied in analytical chemistry for its superior speed and simplicity with little sacrifice in accuracy and precision. Promethazine hydrochloride (PMH) forms PMH-tetraphenylboron (TPB) collosol quantitatively with sodium TPB (Na-TPB) in an acidic medium. The reaction between PMH and Na-TPB reveals a 1:1 molar ratio by Job-Asmus graphing method and nuclear magnetic resonance spectroscopy. However, there is now no accurate method available to determine the titration end-point. Therefore, nonaqueous titration, potentiometric titration, nonaqueous potentiometric titration, spectrophotometry and high-performance liquid chromatography are used in pharmacopeias. The instrumental method is generally not as accurate and precise as the titrimetry in macro analyses. Besides, the aprotic solvents are expensive, irritative and pollutional.In the present study, an accurate, rapid and simple method, highly accurate nephelometric titration was used for PMH quantitation. In the titration, an internal nephelometric sensor was immersed in the titrate to monitor the change in theintensity of the scattered light during the titration. After adding the first drop of the Na-T'PB solution, the PMH solution became cloudy, and, as the titration continued, the scattered light detected increased gradually. If the solubility of the colloid were small enough, the scattered light would reach a maximum at the stoichiometric point. As more titrant was added after passing the point, the solution would not become cloudier and the scattered light would not increase; on the contrary, the scattered light would decrease in intensity because of the dilution of the solution. A peak would appear at the stoichiometric point in the profile of relative intensity of scattered light versus the volume of titrant and therefore the end-point of the titration could be determined accurately.Because the accuracy and precision of highly accurate nephelometric titration depend on the solubility of precipitation, the solubility product constant (Ksp) of PMH-TPB was determined to be 2.66 X 10~10 by the conductivity in our experiment. The titration operating conditions were studied. A relative error as well as deviation is within 0.2% under the experimental conditions. The proposed method has been validated and found to be accurate, precise, specific and linear.