Barbara Tatar’s research while affiliated with Jagiellonian University and other places

Vanadium is an element that has an effect on improving glucose levels in animals with diabetes. However, its operation is strongly dependent on the chemical structure of compounds of this element. The influence of newly synthesized vanadium compounds on biochemical processes is also unknown. The paper presents the influence of eight new vanadium compounds on organ weights of animals (mice NZO) in whom diabetes was induced by a high-fat diet during 8 weeks. Tested vanadium complexes were administered by 5 weeks. After this time organs were collected and weighed. Tested complexes had a remarkable different effect on organ weights, despite having similar composition ([VO(L)(phen)] and the same co-ligand (1,10-phenanthroline). This indicate on separate metabolic pathways of these compounds in the body of tested animals and role of the tridentate L Schiff base ligands. The compounds C2, C3 and C5 shoved biggest influence on organs weight and these results suggest influence on the metabolic pathways and therefore are interesting for further investigations.

For elemental impurities that have been studied for transcutaneous absorption, the available data are rarely suitable for proper toxicological risk assessment – there are multiple factors that can influence this dermal absorption. Hence, in our studies we applied generic and conservative approach - cutaneous permitted daily exposure (CPDE) described in directive International Conference on Harmonisation’s Q3D Guideline on Elemental Impurities (ICH Q3D). The aim of this article is toxicological risk assessment (TRA) of dermal exposure of patients exposed to nickel and chromium due to application of ointments with Marjoram herb extract ( Majoranae herbae extractum ) available in Polish pharmacies ( n = 5, because only five manufacturers produce this kind of pharmaceutical products in Poland). To make the appropriate TRA approach, we considered (1) - raw results (metal per kg of ointment), (2) one-time administration of applied ointments, and (3) daily exposure versus CPDE. Due to the fact the concentrations of Ni generally present in cutaneous products as impurities are not considered sufficient to induce sensitization, the cutaneous and transcutaneous concentration limits (CTCLs) approach was applied for this element assessment. The toxicological analysis was carried out using microwave-assisted wet digestion with concentrated nitric acid and electrothermal atomisation atomic absorption spectrometry. Our results show that, the ointments with Marjoram herb extract from pharmacies in Poland do not represent a real health hazard to patients, however there may be a requirement for the monitoring of impurities of nickel in future. To the best of our knowledge, this paper is the first study about nickel and chromium content in ointments with with Marjoram herb extract (Majoranae herbae extractum).

The toxicological risk assessment (TRA) of elemental impurities (EI) in especially herbal medicinal products (HMP) is a significant challenge for pharmaceutical industry. In Europe very popular are traditional HMP with Valerian root ( Valeriana officinalis L., radix) for relief of mild symptoms of mental stress and to aid sleep. The aim of our unique article is the comprehensive TRA of Cu, Mn and Zn as EI in HMP with V. officinalis L., radix available in Polish pharmacies. This article is a continuation of our previously conducted studies about TRA of heavy metals (Pb and Cd) in these same samples. Investigated elements were determined by Flame Atomic Absorption Spectrometry (F AAS). The values of the correlation coefficients (R > 0.998) confirms the linearity of the applied instrument for precision and accuracy of results. The recoveries, LOD and LOQ values were acceptable. Our results show that all investigated HMP with Valerian root available in Polish pharmacies contain Cu (0.16 – 0.23 mg/L), Mn (0.11 – 0.76 mg/L) and Zn (0.22 – 0.48 mg/L) at a very low level. Based on our estimation of EI including single dose (μg/20 mL) and estimated daily intake (μg/day), our results confirm the safety of all pharmaceuticals. To the best of our knowledge, the Cu, Mn and Zn impurities profile in HMP with V. officinalis L., radix is described for the first time . The applied methodology and results are extremely important from regulatory toxicology point of view (ICH Q3D elemental impurities guideline for pharmaceuticals).

Essential elements like Cu, Mn and Zn are extremely important for herbs growth and physiological functions, however from a toxicological point of view, the exposure of these elements (as essential elemental impurities) can exhibit potential harmful effects for patients. In Europe very popular are ointments with Marjoram herb extract (Majoranae herbae extractum) as herbal medicinal products for adjunctively in rhinitis (runny nose). Based on posology of ointments with Marjoram herb extract, the exposure to these elemental impurities may be high during long-term use. Hence, the aim of this article is the health risk assessment of essential elemental impurities (Cu, Mn and Zn) through the dermal exposure of ointments with Marjoram herb extract (Majoranae herbae extractum) as herbal medicinal products applied adjunctively in rhinitis available in Polish pharmacies. Investigated essential elements were determined by well validated methodology (R > 0.997, recoveries, LOD and LOQ values were acceptable) based on Flame Atomic Absorption Spectrometry (F AAS). Our results indicated that all analyzed herbal medicinal products with Marjoram herb extract available in Polish pharmacies contain relatively low levels of essential element impurities, i.e.: Cu (0.14 – 0.49 mg/kg), Mn (0.31 – 2.57 mg/kg) and Zn (0.73 – 3.19 mg/kg). The estimated exposure of investigated elemental impurities confirm the safety of all products. To the best of our knowledge, the study about Cu, Mn and Zn contents in HMPs with Majoranae herbae extractum is described for the first time. The applied methodology and results are extremely important from regulatory toxicology point of view due to ICH Q3D elemental impurities guideline for pharmaceuticals.

Studies related to the toxicological risk assessment (TRA) of heavy metals impurities (HMIs) in pharmaceuticals is an important issue but there is a lack of refereed literature around the safety of Valeriana officinalis L., radix (Valerian root) as herbal medicinal product (HMP) for the relief of mild nervous tension and sleep disorders according to lead and cadmium impurities. The aim of the study was to estimate the TRA of lead and cadmium in Valeriana officinalis L., radix (Valerian root) as HMP (n = 5) available in Polish pharmacies. In the case of herbal pharmaceuticals, it is particularly important to control the level of HMIs accumulated during the plant’s growth. Perhaps, the exposure for a single dose is not relevant, however justification of our studies is fact that herbal therapies are usually long term. Therefore, even small HMIs doses as present in particular plant may accumulate in patient body over a long period of time. Levels of lead and cadmium were measured by electrothermal atomization atomic absorption spectrometry. The levels of lead and cadmium as HMIs (independently of the producer and declared composition) are quite similar. Our results are satisfactory, confirming the safety of Valeriana officinalis L., radix (Valerian root) as herbal medicinal product for the relief of mild nervous tension and sleep disorders available in Polish pharmacies according to ICH guideline Q3D. To the best of our knowledge, this paper is the first study about lead and cadmium content as HMIs in HMPs containing Valeriana officinalis L., radix (Valerian root).

Scientific reports about elemental impurities in final pharmaceutical products are essential from a regulatory point of view; unfortunately, there is a lack of studies about this important toxicological topic. The aim of our short communication was determination of total Cr impurities in traditional herbal medicinal products (THMP) with Thymi herba (Thymus vulgaris L. and Thymus zygis L.) available in Polish pharmacies (n = 6, because only six manufacturers produce this kind of pharmaceutical products in Poland). The total content of Cr impurities was determined by atomic absorption spectrometry using electrothermal atomisation (ETAAS). Applied comprehensive toxicological risk assessment was based on three main tiers: Tier 1) the comparison of raw results as total Cr impurities profile (metal per L of THMP) with ICH Q3D guideline standards; Tier 2) the estimation of total Cr exposure with a single dose and Tier 3) the estimation of total Cr daily exposure. We confirmed that total Cr impurities were present in all analysed THMP with thymi herba (the observed level was below 6.0 µg/L). Total Cr concentration in a single dose can be deceptively high in comparison to the raw results but is not a threat to patients (20.15 – 63.45 ng/single dose). Moreover, the estimation of total Cr daily exposure shows that all analysed THMP are characterized by daily dose (40.30 – 181.41 ng/day) below PDE value (10700 mg/day); hence all products meet the standards of ICH Q3D elemental impurities guideline.

The Plantago lanceolata L., folium (ribwort plantain) is an active pharmaceutical ingredient in traditional herbal medicinal products (THMP) available in pharmacies as demulcent for the symptomatic treatment of oral or pharyngeal irritations and associated dry cough. This kind of THMP is widely applied among the European population, however, recently voices have been heard in the public about the alleged cadmium impurities. The idea of our study was comprehensive risk assessment of the Cd impurities exposure and its effect on the human health. Our assessment strategy was based on regulatory aspects (raw results versus limits set by FAO/WHO for herbal medicines) and toxicological risk assessment approach based on ICH Q3D guideline foe elemental impurities in final pharmaceutical products. The cadmium was determined by electrothermal atomization atomic absorption spectrometry based on our previously described methodology. Obtained results shows that all analysed THMP with P. lanceolata L., folium available in the Polish pharmacies contain cadmium impurities, but at a very low level (ranged 0.73 - 20.6 μg/L). The content of Cd in single dose (ng/single dose) is also very low and is not a threat to patients. The estimated maximum daily exposure (ng/day) of Cd based on the ‘worst-case scenario’ (maximum concentrations by oral administration) meets the standards of ICH Q3D guideline (all results were below oral permitted daily exposure; PDE for Cd, i.e. < 5.0 µg/day). It can be concluded that all analysed samples of THMP with P. lanceolata L., folium should not represent any health hazard to the patients due to cadmium levels. To the best of our knowledge, this is the first study about Cd impurities level in THMP with P. lanceolata L., folium (ribwort plantain leaves) available in European pharmacies.

Elemental impurities (EIs) profiling in final pharmaceutical products is often not adequately treated, however it is crucial problem in pharmaceutical analysis by reason of the various regulatory authorities (like ICH Q3D guideline). EIs in pharmaceuticals may arise from numerous sources of which the herbal ingredients are not a frequent subject of pharmaceutical analyses. However, based on number of traditional use registrations per year for herbal medicinal products (HMPs) in the EU, it can be stated that monocomponent HMPs are still very popular for use. Due to the high frequency of use, exposure to EIs from HMPs may be high during long-term use. The aim of our article was Ni and Cr impurities profiling of Valeriana officinalis L., radix (Valerian root) as an example of the HMP available in Polish pharmacies for the relief of mild nervous tension and sleep disorders. The choice of metals was justified by: (1) a single dose of Ni administered via oral route can induce dermatitis in nickel-sensitised individuals; (2) Cr is a very problematic element from toxicological point of view. Our results indicate that the standards of the ICH Q3D guideline are met for all EIs.

Vanadium is an element that has an effect on improving glucose levels in animals with diabetes. However, its operation is strongly dependent on the chemical structure of compounds of this element. The influence of newly synthesized vanadium compounds on biochemical processes is also unknown. The paper presents the influence of eight new vanadium compounds on organ weights of animals (mice NZO) in whom diabetes was induced by a high-fat diet during 8 weeks. Tested vanadium complexes were administered by 5 weeks. After this time organs were collected and weighed. Tested complexes had a remarkable different effect on organ weights, despite having similar composition ([VO(L)(phen)] and the same co-ligand (1,10-phenanthroline) . This indicate on separate metabolic pathways of these compounds in the body of tested animals and role of the tridentate L Schiff base ligands. The compounds C2, C3 and C5 shoved biggest influence on organs weight and these results suggest influence on the metabolic pathways and therefore are interesting for further investigations.

Background Prescription food for special medical purposes (FSMPs) and modified milk products (MMPs), available in pharmacies, are important for newborns and infants that are not breastfed. In the scientific literature there is a lack of comprehensive studies and corresponding safety assessment of the essential trace elements in these products. Objective The aim of this article was determination of Cu, Mn and Zn levels in the most frequently available prescription FSMPs (n = 6) and MMPs (n = 6) available in Polish pharmacies. Methods Flame absorption spectrometry (FAAS) following microwave induced digestion (concentrated nitric acid) was applied to determine the levels of the elements in the products. Results Our studies are based on a triple approach (1) the “raw results” of Cu, Mn and Zn levels (products in powdered form), (2) single intake - the level of each essential trace element consumed in one portion, (3) the daily intake depending on age and weight including comparison with Adequate Intake established by European Food Safety Authority. Conclusion The results show the occurrence of differences between the manufacturer’s declared composition and the finished product for consumption. The prescription FSMPs in comparison to MMPs available in Polish pharmacies contain similar levels of Cu, Mn and Zn. Our results show additionally that all of the products do not represent a health hazard to the newborns and infants. This is a pioneer study in terms of the safety assessment, and quality of prescription FSMPs and MMPs available in Polish pharmacies from toxicological and nutritional point of view.