The Impact of Phospholipid-Based Liquid Crystals' Microstructure on Stability and Release Profile of Ascorbyl Palmitate and Skin Performance.

The drug delivery potential of liquid crystals (LCs) for ascorbyl palmitate (AP) was assessed, with the emphasis on the AP stability and release profile linked to microstructural rearrangement taking place along the dilution line being investigated by a set of complementary techniques. With high AP degradation observed after 56 days, two stabilization approaches, i.e., the addition of vitamin C or increasing AP concentration, were proposed. As a rule, LC samples with the lowest water content resulted in better AP stability (up to 52% of nondegraded AP in LC1 after 28 days) and faster API release (~18% in 8 h) as compared to the most diluted sample (29% of nondegraded AP in LC8 after 28 days, and up to 12% of AP released in 8 h). In addition, LCs exhibited a skin barrier-strengthening effect with up to 1.2-fold lower transepidermal water loss (TEWL) and 1.9-fold higher skin hydration observed in vitro on the porcine skin model. Although the latter cannot be linked to LCs' composition or specific microstructure, the obtained insight into LCs' microstructure contributed greatly to our understanding of AP positioning inside the system and its release profile, also influencing the overall LCs' performance after dermal application.

Simple HPLC-UV Method for Therapeutic Drug Monitoring of 12 Antiepileptic Drugs and Their Main Metabolites in Human Plasma.

The objective of the present report was to develop and validate a simple, selective, and reproducible high-performance liquid chromatography method with UV detection suitable for routine therapeutic drug monitoring of the most commonly used antiepileptic drugs and some of their metabolites. Simple precipitation of plasma proteins with acetonitrile was used for sample preparation. 10,11-dihydrocarbamazepine was used as an internal standard. Chromatographic separation of the analytes was achieved by gradient elution on a Phenyl-Hexyl column at 40 °C, using methanol and potassium phosphate buffer (25 mM; pH 5.1) as a mobile phase. The method was validated according to the FDA guidelines for bioanalytical method validation. It showed to be selective, accurate, precise, and linear over the concentration ranges of 1-50 mg/L for phenobarbital, phenytoin, levetiracetam, rufinamide, zonisamide, and lacosamide; 0.5-50 mg/L for lamotrigine, primidone, carbamazepine and 10-monohydroxycarbazepine; 0.2-10 mg/L for carbamazepine metabolites: 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine and carbamazepine-10,11-epoxide; 0.1-10 mg/L for oxcarbazepine; 2-100 mg/L for felbamate and 3-150 mg/L for ethosuximide. The suitability of the validated method for routine therapeutic drug monitoring was confirmed by quantification of the analytes in plasma samples from patients with epilepsy on combination antiepileptic therapy.

Forced Solid-State Oxidation Studies of Nifedipine-PVP Amorphous Solid Dispersion.

In the present study, the oxidative degradation behavior of nifedipine (NIF) in amorphous solid dispersions (ASDs) prepared with poly(vinyl pyrrolidone) (PVP) with a short (K30) and a long (K90) chain length was investigated. The ASDs were prepared via dry ball-milling and analyzed using Fourier transform infrared (IR) spectroscopy, X-ray scattering, and differential scanning calorimetry. The ASDs were exposed to accelerated thermal-oxidative conditions using a pressurized oxygen headspace (120 °C for 1 day) and high temperatures at atmospheric pressure (60-120 °C for a period of 42 days). Additionally, solution-state oxidative degradation studies showed that pure NIF degrades to a greater extent than in the presence of PVP. Electronic structure calculations were performed to understand the impact of drug-polymer intermolecular interactions on the autoxidation of drugs. While no drug degradation was observed in freshly prepared ASD samples, alkyl free radicals were detected via electron paramagnetic resonance (EPR) spectroscopy. The free radicals were found to be consumed to a greater extent by PVP K30- than PVP K90-based ASDs upon exposure to high oxygen pressures. This was consistent with the greater solid-state oxidative degradation of NIF observed in ASDs with PVP K30 than with PVP K90. As no drug recrystallization occurred during this study period, the lower glass-transition temperature and presumed greater molecular mobility of PVP K30 and its ASD as compared to the PVP K90 system appear to contribute to the greater drug degradation in PVP-K30-based ASDs. The extent and the rate of oxidative degradation were higher in the case of PVP-K30-based ASD as compared to that in PVP-K90-based ASD, and the overall degradation increased with an increase in temperature. IR spectral analysis of drug-polymer interactions supports the electronic calculations of the oxidation process. We infer that, apart from the initial free radical content, the difference in the extent of drug-polymer intermolecular interactions in ASDs and amorphous stabilization during the forced oxidation experiments contribute to the observed differences in the autoxidative reactivity of the drug in ASDs with different PVP chain lengths. Overall, the chemical degradation of NIF in ASDs with two PVP chain lengths obtained from accelerated solid-state oxidation studies was in qualitative agreement with that obtained from long-term (3 years) storage under ambient conditions. The study highlights the ability of accelerated processes to determine the oxidative degradation behavior of polymeric ASDs and suggests that the polymer chain length could factor into chemical as well as physical stability considerations.

Vitamin B12 in Foods, Food Supplements, and Medicines-A Review of Its Role and Properties with a Focus on Its Stability.

Vitamin B12, also known as the anti-pernicious anemia factor, is an essential micronutrient totally dependent on dietary sources that is commonly integrated with food supplements. Four vitamin B12 forms-cyanocobalamin, hydroxocobalamin, 5'-deoxyadenosylcobalamin, and methylcobalamin-are currently used for supplementation and, here, we provide an overview of their biochemical role, bioavailability, and efficacy in different dosage forms. Since the effective quantity of vitamin B12 depends on the stability of the different forms, we further provide a review of their main reactivity and stability under exposure to various environmental factors (e.g., temperature, pH, light) and the presence of some typical interacting compounds (oxidants, reductants, and other water-soluble vitamins). Further, we explore how the manufacturing process and storage affect B12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B12 products on the market. We also provide an overview of the approaches toward their stabilization, including minimization of the destabilizing factors, addition of proper stabilizers, or application of some (innovative) technological processes that could be implemented and contribute to the production of high-quality vitamin B12 products.

Design of experiments and multivariate analysis approach to study dissolution stability of a modified-release drug product to support lean design strategies.

OBJECTIVE: The purpose of this paper is to present the use of Design of Experiments and multivariate analysis for evaluation of a modified-release drug product stability to support post-approval lean stability approaches. The focus of the paper was to investigate potential root-causes for acceleration of dissolution upon stability. METHODS: For statistical evaluation of stability data, multiple linear regression statistics was used. The design space of the stability study was modeled using MODDE 12.1 software. For experimental set-up, parameters such as Temperature, Time, Packaging, Batch, and Active Pharmaceutical Ingredient supplier were selected. RESULTS: With multiple linear regression modeling of the all generated stability data until six months, we were able to identify or confirm the Stability-related quality attributes and Shelf life limiting attributes. From the multiple linear regression correlation coefficients, we have evaluated that decrease of an antioxidant upon stability could cause potential shift in dissolution. However, main factors for accelerated dissolution can be attributed to other material and process variables. In the last part of the study, we have shown the usefulness of these methodologies for supporting lean stability approaches. With enhanced drug product knowledge, we designed two reduced long-term stability studies and showed that with 'One-half' reduced design, we would still be able to confirm 24-month shelf life. CONCLUSIONS: Implementing Quality by design approaches on stability studies could reduce the need for excessive analytical testing, help to evaluate meaningfulness of the data and set a risk-based stability testing strategy.

Spherical Agglomerates of Lactose Reduce Segregation in Powder Blends and Improve Uniformity of Tablet Content at High Drug Loads.

We report here on improved uniformity of blends of micronised active pharmaceutical ingredients (APIs) using addition of spherical agglomerates of lactose and enhanced blend flow to improve tablet content uniformity with higher API loads. Micromeritic properties and intra-particle porosity (using nano-computed X-ray tomography) of recently introduced spherical agglomerates of lactose and two standard lactose grades for the direct compression processes were compared. Powder blends of the individual lactose types and different micronised API drug loads were prepared and subjected to specific conditions that can induce API segregation. Tablet content uniformity during direct compression was related to the lactose material attributes. The distinctive micromeritic properties of the lactose types showed that spherical agglomerates of lactose had high intra-particle porosity and increased specific surface area. The stability of binary blends after intense sieving was governed by the intra-particle porosity and surface roughness of the lactose particles, which determined the retention of the model substance. Greater intra-particle porosity, powder specific surface area, and particle size of the spherical agglomerates provided greater adhesion of micronised particles, compared to granulated and spray-dried lactose. Thus the spherical agglomerates provided enhanced final blend flow and uniformity of tablet content at higher drug loads.

Prediction of saxagliptin stability using a new approach based on Partial Least Squares and Design of Experiments.

The objective of this study was to assess the possibility of applying Partial Least Squares (PLS) statistics with the use of experimental design approach towards stability evaluation of the Saxagliptin drug product. The influences of temperature, time, dose, packaging, batch, and oxygen protection were analyzed for identification of critical factors responsible for degradation of saxagliptin and prediction of impurity levels at various storage conditions. Predicted levels of the impurity DP-2 were lower for at least 0.2 % when the drug product was protected from oxygen after its manufacture. Additionally, the PLS model revealed that the lower strength is at least twice less stable concerning impurity DP-1. Based on this analysis shelf life for Zone II was proposed at 24 months with high reliability. Comparison of the PLS model estimates with the measured stability data at shelf life revealed good predictive ability of the developed model. Moreover, PLS predictions of DP-1 and Total impurities were more accurate than those obtained with a standard linear least squares regression, while DP-2 predictions were at least as accurate. We can thus propose a more extensive use of this approach for stability evaluation of pharmaceuticals.

Applying the methodology of Design of Experiments to stability studies: a Partial Least Squares approach for evaluation of drug stability.

The aim of the present research is to show that the methodology of Design of Experiments can be applied to stability data evaluation, as they can be seen as multi-factor and multi-level experimental designs. Linear regression analysis is usually an approach for analyzing stability data, but multivariate statistical methods could also be used to assess drug stability during the development phase. Data from a stability study for a pharmaceutical product with hydrochlorothiazide (HCTZ) as an unstable drug substance was used as a case example in this paper. The design space of the stability study was modeled using Umetrics MODDE 10.1 software. We showed that a Partial Least Squares model could be used for a multi-dimensional presentation of all data generated in a stability study and for determination of the relationship among factors that influence drug stability. It might also be used for stability predictions and potentially for the optimization of the extent of stability testing needed to determine shelf life and storage conditions, which would be time and cost-effective for the pharmaceutical industry.

Novel HPLC-UV Method for Simultaneous Determination of Fat-soluble Vitamins and Coenzyme Q10 in Medicines and Supplements.

A precise, accurate and rapid HPLC-UV method for simultaneous determination of fat-soluble vitamins (vitamin D3, E-acetate, K1, ß-carotene, A-palmitate) and coenzyme Q10 was developed and validated according to ICH guidelines. Optimal chromatographic separation of the analytes in minimal analysis time (8 min) was achieved on a Luna C18 150 × 4.6 mm column using a mixture of acetonitrile, tetrahydrofuran and water (50:45:5, v/v/v). The described reversed phase HPLC method is the first published for quantification of these five fat-soluble vitamins and coenzyme Q10 within a single chromatographic run. The method was further applied for quantification of the analytes in selected liquid and solid dosage forms, registered as nutritional supplements and prescription medicines, which confirmed its suitability for routine analysis.

Simple and sensitive high performance liquid chromatography method with fluorescence detection for therapeutic drug monitoring of topiramate.

A simple, sensitive, accurate, precise and inexpensive HPLC method with fluorescence detection, suitable for routine therapeutic drug monitoring (TDM) of an antiepileptic drug topiramate, was developed and validated. The determination of plasma topiramate concentration was carried out after precolumn derivatization, using 4-chloro-7-nitrobenzofurazan as a fluorescent labeling agent and bendroflumethiazide as an internal standard. The standard calibration curve was linear over the concentration range of 0.01-24 µg/mL (r² > 0.9998). The intra- and inter-day accuracies expressed as bias were from 1.4 to 9.9% and from 1.9 to 10.2%, respectively. The intra- and inter-day precisions were below 7.9% and 2.7%, respectively. The validated method was applied for the measurement of plasma topiramate concentrations in patients with epilepsy. The reported method is appropriate for TDM of topiramate as well as for pharmacokinetic and bioequivalence studies.

A comprehensive approach for N-nitrosamine determination in pharmaceuticals using a novel HILIC-based solid phase extraction and LC-HRMS.

N-nitrosamines (NAs) are potentially highly carcinogenic compounds that have recently been detected in traces in various drug products (DPs). Due to the different physicochemical properties of NAs and active pharmaceutical ingredients (APIs), there is a lack of appropriate analytical methods for simultaneously determining multiple NAs in various DPs. To overcome these limitations, a versatile and innovative analytical approach was developed using a unique sample clean-up procedure by solid phase extraction based on hydrophilic interaction chromatography, which retains high amounts of APIs and polar excipients while allowing NAs of interest to pass through. The samples were analyzed by liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry. The proposed highly sensitive, selective, and robust method was successfully validated, resulting in excellent linearity (R2 > 0.999), accuracy (85-115 %), and precision (RSD <10 %) with adequate recoveries (>80 %), achieving limits of quantitation of at least 42.5 % of regulatory limits. Furthermore, robustness was confirmed for ten DPs (recoveries >80 % and RSD <15 % for all NAs), including those containing up to three APIs. The analytical approach was utilized to examine 26 commercially available and expired DPs. Three NAs (N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine, and N-nitroso-di-n-butylamine) were detected, only NDMA exceeded the limits in expired DPs by up to 32-fold. It was found that special care should be taken when handling samples as NDMA content can be decreased by almost 50 % if samples are not prepared immediately. The approach was tested on 59 different APIs and was confirmed as reliable tool for routine monitoring of 15 NAs in various DPs. Due to its flexibility, the method can be further adapted to the specific API of interest or extended to the newly emerging NA drug substance-related impurities to ensure the safety of DPs and thereby mitigate potential health risks.

The Incorporated Drug Affects the Properties of Hydrophilic Nanofibers.

Hydrophilic nanofibers offer promising potential for the delivery of drugs with diverse characteristics. Yet, the effects of different drugs incorporated into these nanofibers on their properties remain poorly understood. In this study, we systematically explored how model drugs, namely ibuprofen, carvedilol, paracetamol, and metformin (hydrochloride), affect hydrophilic nanofibers composed of polyethylene oxide and poloxamer 188 in a 1:1 weight ratio. Our findings reveal that the drug affects the conductivity and viscosity of the polymer solution for electrospinning, leading to distinct changes in the morphology of electrospun products. Specifically, drugs with low solubility in ethanol, the chosen solvent for polymer solution preparation, led to the formation of continuous nanofibers with uniform diameters. Additionally, the lower solubility of metformin in ethanol resulted in particle appearance on the nanofiber surface. Furthermore, the incorporation of more hydrophilic drugs increased the surface hydrophilicity of nanofiber mats. However, variations in the physicochemical properties of the drugs did not affect the drug loading and drug entrapment efficiency. Our research also shows that drug properties do not notably affect the immediate release of drugs from nanofibers, highlighting the dominant role of the hydrophilic polymers used. This study emphasizes the importance of considering specific drug properties, such as solubility, hydrophilicity, and compatibility with the solvent used for electrospinning, when designing hydrophilic nanofibers for drug delivery. Such considerations are crucial for optimizing the properties of the drug delivery system, which is essential for achieving therapeutic efficacy and safety.

A robust analytical method for simultaneous quantification of 13 low-molecular-weight N-Nitrosamines in various pharmaceuticals based on solid phase extraction and liquid chromatography coupled to high-resolution mass spectrometry.

Recently, the potentially highly carcinogenic N-nitrosamines (NAs) have become the focus of pharmaceutical regulatory authorities, the pharmaceutical industry and researchers because trace amounts have been detected in some drug products (DPs), resulting in drug supply shortages. In the absence of sufficient analytical methods for the determination of multiple regulated low-molecular-weight NAs in various DPs, a robust, selective, sensitive and accurate method based on sample preparation by solid phase extraction, followed by liquid chromatography high-resolution mass spectrometry for the simultaneous analysis of 13 regulated low-molecular-weight NAs was developed. The best results for the cleanup were obtained using Strata X-C SPE cartridge. The proposed method was successfully validated according to the USP general chapter 〈1469〉, demonstrating its excellent linearity, accuracy and precision in wide analytical ranges, adjusted to NAs acceptable intake limits. The achieved limits of quantitation correspond to 30 % or less of the acceptable intake limits. The developed analytical method was applied to 16 commercially available DPs containing one to three active pharmaceutical ingredients with different physicochemical properties. Only N-Nitrosodimethylamine was detected in DPs containing ranitidine at levels exceeding the regulatory AI limits by 37.6 - 57.4-fold. In addition, the robustness of the method was confirmed on a considerable number of DPs containing different active ingredients, demonstrating the suitability of the analytical method for routine quality control of different DPs, thus mitigate the risk to human health.

Matrixing Designs for Shelf-Life Determination of Parenteral Drug Product: A Comparative Analysis of Full and Reduced Stability Testing Design.

This article highlights the applicability of matrixing designs in stability studies for parenteral medications. The traditional approach involves extensive testing over the product's shelf-life. However, matrixing designs offer an alternative approach where only a fraction of samples is tested at each time point. The study conducted in this article focused on three parenteral medications and examined stability data under long-term condition. Degradation products were identified as critical parameter, and kinetics of degradation varied among the selected products. A systematic methodology was adopted to evaluate the data using different matrixing designs. The regression models obtained were assessed using statistical parameters S and R2. Also, each of the 28 matrixing designs were compared to the full design with statistical parameter RMSE and the shelf-life. The results confirmed that each of the evaluated matrixing designs can be applied, whether degradation product shows a linear or non-linear increase, and demonstrated that a reduction of two time points per batch is the most appropriate. In conclusion, this research contributes to the understanding of utilizing reduced matrixing designs in stability studies for parenteral medications and can be an effective strategy to reduce costs and time of stability testing while maintaining the necessary level of precision and reliability.

An LC-MS/MS Method for Quantification of Lamotrigine and Its Main Metabolite in Dried Blood Spots.

BACKGROUND: The antiepileptic drug lamotrigine (LTG) shows high pharmacokinetic variability due to genotype influence and concomitant use of glucuronidation inducers and inhibitors, both of which may be frequently taken by elderly patients. Our goal was to develop a reliable quantification method for lamotrigine and its main glucuronide metabolite lamotrigine-N2-glucuronide (LTG-N2-GLU) in dried blood spots (DBS) to enable routine therapeutic drug monitoring and to identify altered metabolic activity for early detection of drug interactions possibly leading to suboptimal drug response. RESULTS: The analytical method was validated in terms of selectivity, accuracy, precision, matrix effects, haematocrit, blood spot volume influence, and stability. It was applied to a clinical study, and the DBS results were compared to the concentrations determined in plasma samples. A good correlation was established for both analytes in DBS and plasma samples, taking into account the haematocrit and blood cell-to-plasma partition coefficients. It was demonstrated that the method is suitable for the determination of the metabolite-to-parent ratio to reveal the metabolic status of individual patients. CONCLUSIONS: The clinical validation performed confirmed that the DBS technique is a reliable alternative for plasma lamotrigine and its glucuronide determination.

N-Acetylcysteine Ineffective in Alleviating Hangover from Binge Drinking: A Clinical Study.

Alcohol hangover (veisalgia) is a fairly common phenomenon. The pathogenesis of veisalgia is not understood and treatment has not yet been established. Occasionally, students take N-acetylcysteine (NAC) before binge drinking to alleviate hangover. The aim of this study was to evaluate the effect of NAC on serum levels of electrolytes, enzymes, oxidative stress biomarkers and symptoms of veisalgia in binge drinking. In this randomized, double-blind, placebo-controlled study, healthy students were randomly assigned into two groups: one receiving NAC and the other receiving a placebo. Blood samples were taken before drinking, 30 min after a 1.5 h long drinking session, and the subsequent morning. Serum levels of electrolytes, urea, enzymes, ethanol, 8-Hydroxydeoxyguanosine (8-OHdG) and N-epsilon-hexanoyl-lysine were measured. The participants completed the Acute Hangover Severity Scale (AHSS) assessment based on symptoms, and 40 students (20 male), aged 23 ± 2 years, were included in the study. Their mean blood ethanol concentration was 1.4 g/kg. Serum sodium levels were increased after drinking, and urea decreased the following morning compared to their levels before drinking in both groups. Serum 8-OHdG levels were increased after drinking and remained elevated until the following morning, compared to the levels before drinking, in both groups. NAC had no effect on sodium, urea and 8-OHdG levels or the symptoms of veisalgia. In conclusion, binge drinking causes a transient increase in serum sodium and as a prolonged increase in oxidative marker 8-OHdG levels. NAC had no effect on the sodium and 8-OHdG levels.

The search for novel proline analogs for viscosity reduction and stabilization of highly concentrated monoclonal antibody solutions.

Administration of monoclonal antibodies (mAbs) is currently focused on subcutaneous injection associated with increased patient adherence and reduced treatment cost, leading to sustainable healthcare. The main bottleneck is low volume that can be injected, requiring highly concentrated mAb solutions. The latter results in increased solution viscosity with pronounced mAb aggregation propensity because of intensive protein-protein interactions. Small molecule excipients have been proposed to restrict the protein-protein interactions, contributing to reduced viscosity. The aim of the study was to discover novel compounds that reduce the viscosity of highly concentrated mAb solution. First, the chemical space of proline analogs was explored and 35 compounds were determined. Viscosity measurements revealed that 18 proline analogs reduced the mAb solution viscosity similar to or more than proline. The compounds forming both electrostatic and hydrophobic interactions with mAb reduced the viscosity of the formulation more efficiently without detrimentally effecting mAb physical stability. A correlation between the level of interaction and viscosity-reducing effect was confirmed with molecular dynamic simulations. Structure rigidity of the compounds and aromaticity contributed to their viscosity-reducing effect, dependent on molecule size. The study results highlight the novel proline analogs as an effective approach in viscosity reduction in development of biopharmaceuticals for subcutaneous administration.

Innovative analytical methodologies for characterizing chemical exposure with a view to next-generation risk assessment.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

A robust multi-residue method for the monitoring of 25 endocrine disruptors at ultra-trace levels in surface waters by SPE-LC-MS/MS.

Estrogenic endocrine disruptors are one of the biggest ecotoxicological threats in water that pose a significant ecological burden and health-risk for humans due to their high biological activity and proven additive effects. Therefore, we have developed and validated the most comprehensive and ultra-sensitive analytical method published to date, for reliable quantification of 25 high-risk endocrine disruptors at their ecologically relevant concentrations: naturally excreted hormones (estradiol, estrone, estriol, testosterone, corticosterone, and progesterone), synthetic hormones used for contraception and menopausal symptoms (ethinylestradiol, drospirenone, chlormadinone acetate, norgestrel, gestodene, tibolone, norethindrone, dienogest, and cyproterone) and bisphenols (BPS, BPA, BPF, BPE, BPAF, BPB, BPC, and BPZ). It is based on a solid-phase extraction of water samples, followed by a robust dansyl chloride derivatization with detection by liquid chromatography-tandem mass spectrometry with a single sample preparation and two analytical methods using the same analytical column and mobile phases. The achieved limits of quantitation are in the sub-ng L-1 range, and detection limits as low as 0.02 ng L-1, meeting the newest proposal for environmental quality standards (EQS) by the EU water framework directive for estradiol and ethinylestradiol. The method was extensively validated and applied to seven representative Slovenian water samples, where we detected 21 out of 25 analytes; 13 were quantified in at least one sample. Estrone and progesterone were quantified in all samples, reaching levels up to 50 ng L-1; ethinylestradiol was higher than the current EQS (0.035 ng L-1) in three samples, and estradiol was above its EQS (0.4 ng L-1) in one sample, proving the method's applicability and the necessity for monitoring these pollutants.

Content and stability of B complex vitamins in commercial cosmetic products.

BACKGROUND: Individual B vitamins have many favorable effects on the skin and are common cosmetic ingredients. However, their formulation is demanding due to stability issues, which consequently affect the products' quality. AIMS: We aimed to determine the quality (labeling accuracy, content determination, and content-related quality control) and stability under long-term and accelerated storage conditions of a representative sample of commercial cosmetics containing the most common B vitamins - nicotinamide, dexpanthenol, pyridoxine, and cyanocobalamin. METHODS: Cyanocobalamin was determined by a previously published stability-indicating HPLC- diode array detector (DAD) method for the simultaneous determination of all hydrophilic vitamins. This method was additionally simplified and adjusted for the time-effective analysis of nicotinamide, dexpanthenol, and pyridoxine. Both methods were properly validated. RESULTS: All labeled B vitamins were present in the 36 tested products, mostly in contents, reported effective on the skin. Thus, a straightforward correlation between vitamin contents and product prices were not observed. The content-related quality control of eight products, which quantitively specify their content, revealed significantly lower nicotinamide contents (47% and 57%) in two products and appropriate or higher nicotinamide (102%-112%) and dexpanthenol (100%-104%) contents than declared in the remaining products. The 6-month long-term and accelerated stability studies demonstrated the products' physical stability, but also revealed dexpanthenol, pyridoxine, and cyanocobalamin degradation, while nicotinamide was mostly stable in the tested products. CONCLUSIONS: The obtained results provide an inside into the quality of commercial vitamin B cosmetics and highlight the importance of stability testing in the formulation of quality, efficient, and safe cosmetics.