Amlodipine aspartic acid impurity

Toxicity and low entrapment efficiency are the main problems for pharmaceutical applications of catanionic vesicles. In order to minimize surfactant toxicity, increase the drug loading content and simultaneously reduce the need for tedious chemical synthesis, we use oleic acid as the biocompatible surfactant, which reacts with the selected drug molecules (amlodipine) to produce an amphiphilic prodrug molecule for the straightforward fabrication of catanionic vesicles. The prodrug molecules are easily obtained by proton transfer between amlodipine and oleic acid molecules. The characterization of prodrug molecules and their aggregation behaviours in aqueous solutions are investigated by using Fourier transform infrared spectrophotometry (FTIR), 1H-nuclear magnetic resonance (1H-NMR), differential scanning calorimetry (DSC), surface tension measurement, transmission electron microscopy (TEM), dynamic light scattering (DLS), conductivity and zeta potential (ζ). The results demonstrate that vesicles could be easily formed with the prodrug amphiphilic molecules dispersed in aqueous solutions. Particularly, the drug release behaviour of the as-prepared catanionic vesicles exhibits excellent sustained drug release properties, which demonstrates their promising application in the newly designed drug delivery system.

A simple, rapid and sensitive method for chiral separation of the amlodipine racemate was developed. (R)-and (S)-amlodipine enantiomers were separated by achiral HPLC, utilising dual chiral mobile phase additives, within 16 min, which was much faster than the previous similar studies. The method was established on an achiral WondaSil C18 column, using methanol-water (45 : 55 (v/v), pH 2.5) containing 7.5 mmol L−1 sulfobutylether-β-cyclodextrin (SBE-β-CD) and 0.3 mmol L−1 polyethylene glycol-20 000 (PEG-20M) as the mobile phase. Effects of additives and concentration, content of methanol and pH on the enantioseparation were investigated. The method was validated for linearity, repeatability, limits of detection (LOD) and limits of quantification (LOQ). The calibration curve (R(S)2 = 0.9998) was constructed in the range of 10-500 μg mL−1 for (S)-amlodipine. Repeatability (n = 6) showed less than 2% relative standard deviation (R.S.D.). LOD and LOQ were found to be 0.032 and 0.106 μg mL−1 for (S)-amlodipine. This method was flexible, simple and economically advantageous over the use of a chiral stationary phase, and was successfully applied to the determination of the amlodipine enantiomers in a commercial pharmaceutical tablets study.

We have developed a simple UV-visible spectrometric method for parallel detection of four drugs (venlafaxine, imipramine, amlodipine and alfuzosin) by using unmodified gold nanoparticles (Au NPs) as a colorimetric probe. The citrate was self-assembled onto the Au NPs to form a probe that undergoes a color change from red to blue by the addition of the four drugs. It is presumed that the color change is a result of the aggregation of the Au NPs induced by the four drugs, resulting a red-shift in their absorption spectra from 521 to 653, 695, 688 and 636 nm for venlafaxine, imipramine, amlodipine and alfuzosin, respectively. The method was validated in the concentration range of 0.001-100 μM, where it demonstrated good linearity (R2 = 0.997, 0.997, 0.995 and 0.998) with limits of detection in the range of 0.9-9.3 nM. The aggregation of the Au NPs induced by the four drugs was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The applicability of the method was demonstrated by determining the drugs contents in pharmaceutical and biological samples (urine and plasma).