TY  - JOUR
A1  - Walther, Rasmus
A1  - Krmar, Jovana
A1  - Leistner, Adrian
A1  - Svrkota, Bojana
A1  - Otašević, Biljana
A1  - Malenović, Andjelija
A1  - Holzgrabe, Ulrike
A1  - Protić, Ana
T1  - Analytical Quality by Design: achieving robustness of an LC-CAD method for the analysis of non-volatile fatty acids
JF  - Pharmaceuticals
N2  - An alternative to the time-consuming and error-prone pharmacopoeial gas chromatography method for the analysis of fatty acids (FAs) is urgently needed. The objective was therefore to propose a robust liquid chromatography method with charged aerosol detection for the analysis of polysorbate 80 (PS80) and magnesium stearate. FAs with different numbers of carbon atoms in the chain necessitated the use of a gradient method with a Hypersil Gold C\(_{18}\) column and acetonitrile as organic modifier. The risk-based Analytical Quality by Design approach was applied to define the Method Operable Design Region (MODR). Formic acid concentration, initial and final percentages of acetonitrile, gradient elution time, column temperature, and mobile phase flow rate were identified as critical method parameters (CMPs). The initial and final percentages of acetonitrile were fixed while the remaining CMPs were fine-tuned using response surface methodology. Critical method attributes included the baseline separation of adjacent peaks (α-linolenic and myristic acid, and oleic and petroselinic acid) and the retention factor of the last compound eluted, stearic acid. The MODR was calculated by Monte Carlo simulations with a probability equal or greater than 90%. Finally, the column temperature was set at 33 °C, the flow rate was 0.575 mL/min, and acetonitrile linearly increased from 70 to 80% (v/v) within 14.2 min.
KW  - Analytical Quality by Design
KW  - fatty acids
KW  - charged aerosol detector
KW  - polysorbate 80
KW  - magnesium stearate
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311265
SN  - 1424-8247
VL  - 16
IS  - 4
ER  -