Advanced Spectrophotometric Resolution Techniques for a Spectrally Overlapping Spasmolytic Binary Mixture along with Dichloroaniline as a Toxic Impurity: Application to Content Uniformity Testing

Abstract

Background Irritable bowel syndrome (IBS) is considered an anxious disease leading to undesirable pain. Phloroglucinol (PHG) and Trimethylphloroglucinol (TMG) are co-formulated as spasmolytic medication that is considered to be effective in reducing smooth muscle spasm. Dichloroaniline (DCL) is a specified PHG pharmacopoeial impurity which is needed to be monitored to avoid its toxic effects. Objective Different smart approaches were presented as a challenge to provide simple, reliable and economic spectrophotometric methods able to resolve the severe overlapping in the spectra of PHG and TMG in their pure and pharmaceutical forms, in addition to their estimation in the presence of DCL as PHG toxic impurity without any need for initial separation. Methods The presented work include univariate methods; Derivative ratio (DR), Ratio difference (RD), Mean centering (MC) and Deconvulated Fourier method (DF) which were able to determine PHG and TMG simultaneously in their binary mixture after DCL was estimated in the zero order, where the two drugs have zero absorption at 247.0 nm, and its contribution was eliminated by applying ratio subtraction method. Multivariate chemometric PLS and PCR models were also applied to determine PHG and TMG simultaneously in presence of DCL impurity. Results Univariate methods were applied in the range of 5.0–30.0, 2.5–25.0, and 1.0–12.0 µg/mL for PHG, TMG and DCL, respectively. The proposed chemometric models were used in the range of 6.0–14.0, 5.0–25.0 and 2.0–10.0 µg/mL for PHG, TMG and DCL, respectively. These analytical approaches succeeded in estimating the cited drugs in their pharmaceutical formulation and assessing content uniformity of dosage units. The methods were statistically compared with a reported HPLC method, and the results revealed no significance statistical difference. Conclusion This work provides for the first time univariate and multivariate PLS and PCR methods succeeded to assess PHG and TMG in presence of DCL as toxic impurity along with content uniform testing of dosage units. Highlights Comparative univariate and multivariate spectrophotometric analytical approaches was presented, for the first time, for estimation of spasmolytic formulation of PHG and TMG in the presence of Dichloroaniline (DCL) as PHG toxic impurity. Successful application to content uniformity testing of Stopspasm® dosage form. Statistical study including t-test and one way ANOVA was conducted.

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