# Two sustainable chromatographic approaches for estimation of new combination of phenylephrine hydrochloride and doxylamine succinate in presence of doxylamine oxidative degradation product

## TL;DR

This paper introduces two eco-friendly chromatography methods to accurately measure a drug combination in the presence of a degradation product.

## Contribution

The study introduces two sustainable chromatographic methods for quantifying phenylephrine and doxylamine in the presence of an oxidative degradation product.

## Key findings

- RP-HPLC and HPTLC methods were validated for reliable and selective quantification of PHE, DOX, and DOX DEG.
- Both methods demonstrated good linearity and low detection limits for all analytes.
- The methods were confirmed to be sustainable and practical for real-world applications.

## Abstract

A new drug combination of phenylephrine hydrochloride (PHE) and doxylamine succinate (DOX) has been introduced for treating allergic rhinitis. Stability testing is critical for uncovering degradation routes and assessing the stability of combined drugs. This study illustrates the application of two eco-friendly chromatographic techniques which are reversed phase high-performance liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC), for assessing PHE and DOX when DOX oxidative degradation product (DOX DEG) is present. Using liquid chromatography- mass spectroscopy to identify DOX DEG. The HPLC method produced the best separation with isocratic elution and a mobile phase consists of ethanol and 0.01 M phosphate buffer pH = 5.0 (30: 70, v/v), and it was pumped at 1.0 mL/min. The analytes were measured at 260.0 nm using diode array detector (DAD), and the Xterra C18 column (100 mm × 4.6 mm × 5 m) used as a stationary phase. The method demonstrated a linear response for DOX and PHE across a concentration range of 5.00 to 100.00 µg/mL. The range for DOX DEG was 5.00 to 30.00 µg/mL. The limits of detection (LOD) were determined to be 1.44 for DOX, 1.59 for PHE, and 0.84 µg/mL for DOX DEG. Correspondingly, the limits of quantification (LOQ) were 4.32, 4.77, and 2.52 µg/mL for DOX, PHE, and DOX DEG, respectively. The separation in HPTLC was accomplished by combining ethanol, methylene chloride, and ammonia 30% in ratio 7:2.5:0.5 (v/v/v) as a developing system. The drugs were then quantitatively determined at wavelengths of 260.0 nm using UV detector. The linearity range was 4.00–26.00 (µg/band) for DOX and PHE while it was 0.50–10.00 (µg/band) for DOX DEG. Values of LOD were 0.65 ,0.76 and 0.16 µg/band for PHE, DOX, DOX DEG, respectively. While1.95,2.28 and 0.48 µg/band were values of LOQ. Per ICH guidelines, two analytical methods were validated and proven to be reliable, reproducible, and selective. Additionally, sustainability assessments confirmed their green credentials and practical applicability.

The online version contains supplementary material available at 10.1038/s41598-025-22295-6.