HPLC and Chemometrically‐Assisted Spectrophotometric Estimation of Two Binary Mixtures for Combined Hypertension Therapy

Abstract

Three different methods are developed for the determination of felodipine with either (+)–metoprolol tartrate salt or ramipril. The high performance liquid chromatography (HPLC) method depends on the simultaneous separation of each drug in a reverse phase Hypersil BDS C₁₈ 3 µm (150×4.6) column at 25°C. Elution was carried out with a mobile phase consisting of 0.015 M 1‐heptanesulfonic acid sodium salt‐methanol‐acetonitrile (35:40:25, v/v/v, pH 2.5). Optimization of the separation in terms of mobile phase composition is crucial to the method development, which is discussed in detail. Quantitation was achieved with UV detection at 210 nm. Moreover, the resolution of the two binary mixtures separately, has also been accomplished by using a mobile phase consisting of 0.015 M sodium dihydrogen phosphate monohydrate‐methanol‐acetonitrile 40:30:30, v/v/v, at pH 6.5 (λ=230 nm) for the determination of felodipine with metoprolol, and at pH 2.5 (λ=210 nm) for felodipine with ramipril, respectively.

The other two chemometrically‐assisted spectrophotometric methods that have been used were “Derivative‐Ratio” and “Partial Least Squares” PLS. These approaches were successfully applied to quantify each drug in the mixture using the information of the zero order UV spectra between 210–420 nm. Both methods could determine, with linearity, in the range of 1.56–15.60 µg/mL for ramipril, 4.82–80.40 µg/mL for metoprolol, 1.61–17.69 µg/mL for felodipine. They were successfully applied to the “dose uniformity” test of the two binary combinations in commercial tablets.

Keywords:

• Felodipine
• (+)–Metoprolol tartrate
• Ramipril
• HPLC
• Derivative‐Ratio
• Partial Least Squares
• Commercial tablets

Acknowledgment

The authors gratefully acknowledge pharmaceutical company Aventis which kindly provided pure standards felodipine and ramipril.