Development and Validation of a Chromatography Method Using Tandem UV/Charged Aerosol Detector for Simultaneous Determination of Amlodipine Besylate and Olmesartan Medoxomil: Application to Drug-Excipient Compatibility Study.

Ariadne M Brondi,Jerusa S Garcia,Marcello G Trevisan

doi:10.1155/2017/4878316

Abstract

A study was carried out to investigate compatibility of amlodipine besylate and olmesartan medoxomil with a variety of pharmaceutical excipients. Both drugs are antihypertensive agents that can be administered alone, in monotherapy, or in pharmaceutical association. The studies were performed using binary and ternary mixtures, and samples were stored for 3 and 6 months at 40°C under 75% relative humidity and dry conditions. For this study, a method based on high-performance liquid chromatography (HPLC) was developed and validated for the simultaneous determination of amlodipine besylate and olmesartan medoxomil in samples from pharmaceutical preformulation studies using diode array detector (DAD) and charged aerosol detector (CAD). The runtime per sample was 10 min with retention time of 7.926 min and 4.408 min for amlodipine and olmesartan, respectively. The validation was performed according to ICH guidelines. The calibration curve presents linear dynamic range from 12 to 250 μg mL−1 for amlodipine and from 25 to 500 μg mL−1 for olmesartan with coefficient of determination (R2 ≥ 0.9908) while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.0%. The excipients such as corn starch, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, talc, polyvinylpyrrolidone, lactose monohydrate, and polyethylene glycol showed potential incompatibilities after accelerated stability testing.

Highlights

Amlodipine besylate (AMLO), CAS 111470-99-6, 3-ethyl5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1, 4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulphonate, is a calcium channel blocker used in treatment of hypertension, angina pectoris, and other cardiovascular diseases
E charged aerosol detector (CAD) is a relatively recent technology, and its main characteristic is to be a universal detector for nonvolatile analytes. e response may vary according to the composition of the mobile phase, and there are some limitations about the mobile phase: these may not be saline and the solvent must be volatile. e CAD is a detector independent of the chemical structure, optical properties, and the ionization capacity of the analytes, producing a similar response for di erent compounds, which allows the quanti cation even when there is no standard availability, since the detector measures the amount of charge, which is proportional to the amount of analytes
At diode array detector (DAD), the optimum wavelengths selected were 239 nm and 250 nm for AMLO and Olmesartan medoxomil (OLME), respectively. e typical chromatograms of AMLO and OLME obtained by the high-performance liquid chromatography (HPLC)-based method are presented in Figure 2. e average retention times of OLME and AMLO were 4.336 and 7.854 min, respectively

Summary

Introduction

Amlodipine besylate (AMLO), CAS 111470-99-6, 3-ethyl5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1, 4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulphonate, is a calcium channel blocker used in treatment of hypertension, angina pectoris, and other cardiovascular diseases. E purpose of this work was to develop and validate a sensitive LC method with CAD for determination of AMLO and OLME, which could be applied to drug-excipient compatibility studies. Small changes in chromatographic conditions such as mobile phase (proportion of acetonitrile in 60 ± 2%), column temperature (25 ± 5°C), and ow rate (0.5 ± 0.1 mL min−1) were done to evaluate the robustness of the proposed HPLC method.

Results

Conclusion