Application of supercritical fluid chromatography for separation and quantitation of 15 co‐formulated binary anti‐hypertensive medications using a single elution protocol

Abstract

A facile supercritical fluid chromatography method is proposed to analyse 15 co‐formulated binary anti‐hypertensive drug combinations using a customized elution procedure. The effect of mobile phase composition, column back pressure and temperature was suitably optimized for adequate retention, analyte response and resolution. The chromatographic separation of the different drug combinations was performed on a DCPak poly(4‐vinylpyridine) column (250 × 4.6 mm, 5 μm) at 125‐bar pressure and 40°C using a photodiode array detector. A linear gradient of CO2 and 0.1% formic acid in methanol provided the best elution conditions for all drug combinations. Baseline separation of the drugs was possible with resolution factor Rs ranging from 1.42 to 12.58. The method was validated for specificity, sensitivity, accuracy and precision, recovery and robustness. The limit of detection and limit of quantitation for aliskiren, amlodipine, atenolol, candesartan, hydrochlorothiazide, lisinopril, losartan, metoprolol, olmesartan, telmisartan and valsartan were in the range of 0.26–2.56 and 0.77–7.75 μg/mL, respectively. The thermodynamic study revealed that interactions of the drugs with the stationary phase were spontaneous as evident from the negative free energy values, and the separation process was enthalpy driven. The developed method was successfully employed to analyse these drugs in their co‐formulated tablet formulations.

Columns in analytical‐scale supercritical fluid chromatography: From traditional to unconventional chemistries

“…The polymeric pyridyl group is covalently attached to the silica shielding residual silanol groups [227] and can be reversibly tuned to the cationic pyridinium form via an organic modifier containing trifluoroacetic acid [227]. The poly(4-vinylpyridine) stationary phase was successfully used for the separation of PAH [227], steroids [227], and anti-hypertensive drugs [228,229].…”