Determination of chromatographic conditions for quantitative assessment of active components in complex nasal spray after manufacturing and expiry date

Abstract

The aim of the work is the development of chromatographic conditions, the study of the validation characteristics of the method of quantitative determination of phenylephrine hydrochloride, nitrofural, lidocaine hydrochloride and diphenhydramine hydrochloride, panthenol, povidone in the joint presence in the nasal spray by a complex method of liquid chromatography with UV detection. Evaluation of the quantitative content of active components after manufacturing and during the shelf life.

Materials and methods. Agilent 1260 liquid chromatographs, equipped with a diode-matrix detector from the company "Agilent technologies", USA. Chromatographic columns 250×4.6 mm in size, filled with octadecylsilyl silica gel for chromatography (Zorbax StableBond SB-Aq, Agilent company), mobile phase A - phosphate buffer solution pH 7.0 - acetonitrile P (1650:350), mobile phase B – acetonitrile P; elution mode – gradient; mobile phase flow rate – 1.0 ml/min; detection wavelengths – 220 nm (for panthenol, phenylephrine, povidone, diphenhydramine) and 235 nm (for nitrofural and lidocaine).

Results. Chromatographic separation conditions were developed for the co-presence determination of six target substances: panthenol, phenylephrine hydrochloride, nitrofural, povidone, lidocaine hydrochloride and diphenhydramine hydrochloride. The suitability of the technique for this task was confirmed by determining the validation characteristics. The methodology at the appropriate level is characterized by specificity, linearity, correctness and convergence in the range of application for panthenol (range 20.33-38.26 mg/ml, Δ_Z=0.93 ≤ max Δ_Z=3.20, a=0.63  max a=5.12, r = 0.9978  min r= 0.9924), phenylephrine hydrochloride (range 1,70-3,21 mg/ml, Δ_Z=0.51 ≤ max Δ_Z=3.20, a=0.15  max a=5.12, r = 0.9984  min r= 0.9924), nitrofural (range 0.137-0.257 mg/ml, Δ_Z=0.91 ≤ max Δ_Z=3.20, a=0.032  max a=5.12, r = 0.9987  min r= 0.9924) povidone (range 20,44-38,50 mg/ml, Δ_Z=0.23 ≤ max Δ_Z=3.20, a=2,33  max a=5.12, r = 0.9942  min r= 0.9924), lidocaine hydrochloride (range 6,80-12,81 mg/ml, Δ_Z=0.34 ≤ max Δ_Z=3.20, a=0.66  max a=5.12, r = 0.9988  min r= 0.9924), diphenhydramine hydrochloride (range 1,36-2,56 mg/ml, Δ_Z=0.20 ≤ max Δ_Z=3.20, a=0.15  max a=5.12, r = 0.9980  min r= 0.9924). There are no significant changes when stored at 25 °C for 6 months.

Conclusions. An analytical method of quantitative determination of the component composition in an extemporaneous nasal spray by a complex method of high-performance liquid chromatography has been developed. The determined validation parameters confirm the correctness of the methodology. The chemical stability of the dosage form is observed for 6 months