University of Tasmania
Browse

File(s) under permanent embargo

Method development and validation for optimised separation of salicylic, acetyl salicylic and ascorbic acid in pharmaceutical formulations by hydrophilic interaction chromatography and response surface methodology

journal contribution
posted on 2023-05-17, 12:19 authored by Hatambeygi, N, Abedi, G, Mohammad TalebiMohammad Talebi
This paper introduces a design of experiments (DOE) approach for method optimisation in hydrophilic interaction chromatography (HILIC). An optimisation strategy for the separation of acetylsalicylic acid, its major impurity salicylic acid and ascorbic acid in pharmaceutical formulations by HILIC is presented, with the aid of response surface methodology (RSM) and Derringer’s desirability function. A Box-Behnken experimental design was used to build the mathematical models and then to choose the significant parameters for the optimisation by simultaneously taking both resolution and retention time as the responses. The refined model had a satisfactory coefficient (R2 > 0.92, n = 27). The four independent variables studied simultaneously were: acetonitrile content of the mobile phase, pH and concentration of buffer and column temperature each at three levels. Of these, the concentration of buffer and its crossproduct with pH had a significant, positive influence on all studied responses. For the test compounds, the best separation conditions were: acetonitrile/22 mM ammonium acetate, pH 4.4 (82:18, v/v) as the mobile phase and column temperature of 28 °C. The methodology also captured the interaction between variables which enabled exploration of the retention mechanism involved. It would be inferred that the retention is governed by a compromise between hydrophilic partitioning and ionic interaction. The optimised method was further validated according to the ICH guidelines with respect to linearity and range, precision, accuracy, specificity and sensitivity. The robustness of the method was also determined and confirmed by overlying counter plots of responses which were derived from the experimental design utilised for method optimisation.

History

Publication title

Journal of Chromatography A

Volume

1218

Issue

35

Pagination

5995-6003

ISSN

0021-9673

Department/School

School of Natural Sciences

Publisher

Elsevier Science Bv

Place of publication

PO Box 211, Amsterdam, Netherlands, 1000 Ae

Rights statement

Copyright 2011 Elsevier B.V.

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the chemical sciences

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC