Development and Validation of a Combined Methodology for Assessing the Total Quality Control of Herbal Medicinal Products – Application to Oleuropein Preparations

Abstract

Oleuropein (OE) is a secoiridoid glycoside, which occurs mostly in the Oleaceae family presenting several pharmacological properties, including antioxidant, cardio-protective, anti-atherogenic effects etc. Based on these findings OE is commercially available, as Herbal Medicinal Product (HMP), claimed for its antioxidant effects. As there are general provisions of the medicine regulating bodies e.g. European Medicines Agency, the quality of the HMP’s must always be demonstrated. Therefore, a novel LC-MS methodology was developed and validated for the simultaneous quantification of OE and its main degradation product, hydroxytyrosol (HT), for the relevant OE claimed HMP’s. The internal standard (IS) methodology was employed and separation of OE, HT and IS was achieved on a C18 Fused Core column with 3.1 min overall run time employing the SIM method for the analytical signal acquisition. The method was validated according to the International Conference on Harmonisation requirements and the results show adequate linearity (r2 > 0.99) over a wide concentration range [0.1–15 μg/mL (n=12)] and a LLOQ value of 0.1 μg/mL, for both OE and HT. Furthermore, as it would be beneficial to control the quality taking into account all the substances of the OE claimed HMP’s; a metabolomics-like approach has been developed and applied for the total quality control of the different preparations employing UHPLC-HRMS-multivariate analysis (MVA). Four OE-claimed commercial HMP’s have been randomly selected and MVA similarity-based measurements were performed. The results showed that the examined samples could also be differentiated as evidenced according to their scores plot. Batch to batch reproducibility between the samples of the same brand has also been determined and found to be acceptable. Overall, the developed combined methodology has been found to be an efficient tool for the monitoring of the HMP’s total quality. Only one OE HMP has been found to be consistent to its label claim.

A novel bioanalytical method based on UHPLC‐HRMS/MS for the quantification of oleuropein in human serum. Application to a pharmacokinetic study

“…Two healthy, male physical education students, aged 21 and 22 years and designated as A and B, respectively, received an olive leaf extract enriched in OE in the morning after an overnight fast. Specifically, they ingested 1200 mg of Benolea® EFLA®943 (in the form of four 300 mg capsules), containing a total of 204.4 mg OE (Lemonakis et al , ) and provided 10 mL of venous blood just before ingestion and every 15 min up to 1 h after ingestion, every 30 min between 1 and 3 h, and every 1 h between 3 and 6 h through an indwelling catheter in the forearm (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 h). The subjects were required to avoid intense physical activity and intake of alcohol, medication or nutritional supplements on the previous day.…”

The multifunctional therapeutic potentiality of extra virgin olive oil administration through the intervention in pathophysiological mechanisms: Focus on Alzheimer's disease

“…OLE, another dominant constituent of olive oil is proved to have anti-inflammatory activity [26] and antioxidant activity [5]. Studies showed beneficial outcomes in decrease of coronary atherosclerosis and control blood pressure [27] and it was also explored for its antitumor activity [28].…”

Comparison of Serum Metabolite Changes of Radiated Mice Administered with Panax quinquefolium from Different Cultivation Regions Using UPLC-Q/TOF-MS Based Metabolomic Approach

“…Pharmacology-based metabolomics has the potential not only to study pharmacological effects of herbal plants and their metabolic action mechanisms [ 23 , 24 ] but also to discriminate plant species of the same genus [ 25 , 26 ] and the same plant species from different cultivation regions [ 27 ]. It was also adopted to assess the holistic quality of herbal medicinal products [ 28 ].…”