<p>Osimertinib is a new-generation epidermal growth factor inhibitor for the treatment of non-small cell lung cancer. In the present study, a rapid and sensitive LC with tandem MS method was developed and validated for the determination of osimertinib in rat plasma. Chromatographic separation was carried out on a C18 column using acetonitrile and water containing 0.1% formic acid. The assay was validated over a concentration range of 1.0&#8211;1000 ng/mL for osimertinib, with a lower LOQ of 1.0 ng/mL. The intra- and interday accuracy values for osimertinib ranged from 92.66 to 101.50% and from 97.08 to 99.15%, respectively, and the intra- and interday precision values for osimertinib ranged from 6.25 to 10.34% and from 3.43 to 10.44%, respectively. The method was successfully applied in a pharmacokinetic study of osimertinib after oral administration of osimertinib (4.5 mg/kg) to rats.</p>.

<p>An herbal formula, Huang-Qi-Liu-Yi Tang, is a prescription medicine that has been commonly used for the treatment of prostatitis and condyloma acuminatum over the last thousand years. In this study, response surface methodology, with a Box&#8211;Behnken design (BBD), was used to optimize the decoction conditions of an herbal formula. Astragaloside, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, polysaccharide, and extractum were used as multiple evaluation markers. Soak time, water-to-medicinal herb ratio, and extraction time were determined as the three main variables by single-factor experiments and further optimized to obtain the maximum yields for the six marker compounds. Data from well-designed experiments were fitted to obtain second-order polynomial equations using multiple regression analysis, and the accuracies of these equations were evaluated and verified using statistical methods. By solving the regression equations and analyzing the three-dimensional response surfaces, optimum conditions were obtained and are summarized as follows: soak time of 57 min, water-to-medicinal herb ratio of 9:1 (mL/g), and extraction time of 48 min. Under optimized conditions, the experimental yields of astragaloside, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, polysaccharide, and extractum were 0.13, 0.085, 1.64, 1.56, 72.19, and 25.64%, respectively, which was in good agreement with the values predicted by the BBD.</p>.

The botanical origin of seven types of Slovenian honey was investigated by analysis of their elemental content using k0-instrumental neutron activation analysis. A total of 28 representative samples were collected from beekeepers all over Slovenia in 2 consecutive years. Nineteen of the 37 elements measured were present in amounts above their LOD. The present study suggests that the determination of only alkali elements might be sufficient for the classification of Slovenian honeys according to their botanical origin. Linden and multifloral honeys can be differentiated on the basis of Na content. The differentiation of forest, spruce, and fir honeys is possible on the basis of differences in Cs, K, and Rb content. The difference between Na and Rb content can be used as a discriminating tool between light and dark honeys, because light honeys (black locust, linden, and multifloral) contained more Na than Rb, whereas it was the opposite for dark honeys (chestnut, forest, spruce, and fir). Statistically significant correlations were found between K and Rb and between K and Cs content. This study represents a considerable step in filling the knowledge gap concerning both the determination of elements present in low concentrations and the botanical origin of Slovenian honey.

<p>The aim of this study was to develop and validate a method for the determination of balenine/ophidine (hereafter referred to as &#8220;balenine&#8221;) in whale extracts and muscle samples from Balaenoptera acutorostrata. Further, the goal was to evaluate the method&#39;s applicability for the determination of other histidine-containing dipeptides (HCDs): anserine and carnosine and their amino acids &#960;-methylhistidine, &#964;-methylhistidine, histidine, and &#x3b2;-alanine. For balenine, the LOD and LOQ were found to be 0.03 and 0.1 mg/g, respectively, and the linear range was validated up to 160 mg/g. Trueness was evaluated by spiking experiments with balenine, and the recovery was found to be 88&#8211;90%. A comparison of the results showed that most of the other analytes were within 80&#8211;120% of the value found with the previously developed and validated method. Precision and internal reproducibility for balenine was around 0.9 and 2%, respectively, with measurement uncertainties of 2&#8211;4%. Therefore, the method was found to be fit for purpose for the determination of balenine and other HCDs and their constituent amino acids in whale meat and extracts.</p>.

The present work aims to provide a contribution to the overall investigation of European unifloral honeys with regard to authentication according to botanical and geographical origins. The mineral content of 206 monofloral honey samples of five botanical origins from six different regions in Serbia was investigated by inductively coupled plasma optical emission spectrometry. Chemometric techniques were applied for the classification and differentiation of acacia, sunflower, and linden honey according to botanical origin, as well as acacia honey samples according to regional origin. The highest influence on the differentiation of acacia honey samples was the presence of siderophile and chalcophile elements, whereas sunflower and linden honeys were determined by the presence of lithophile elements, indicating their origin from soil. However, due to the different bioaccumulation properties of plants, the presence of elements is not necessarily directly correlated to their presence in soil, which is confirmed by the results of the authentication of geographical origin of acacia honey.

In recent years, the botanical and geographical origin of food has become an important topic in the context of food quality and safety, as well as consumer protection, in accordance with international standards. Finding chemical markers, especially phytochemicals, characteristic for some kind of food is the subject of interest of a significant number of researchers in the world. This paper is focused on the use of polyphenols as potential markers for the determination of botanical origin of honey. It includes a review of the polyphenols present in various honey samples and the methods for their separation and identification. Special emphasis in this paper is placed on the identification of honey polyphenols using advanced LC-MS techniques in order to find specific markers of botanical origin of honey. In this regard, this study gives an overview of the literature that describes the use of LC-MS techniques for the isolation and determination of honey polyphenols. This review focuses on the research performed in the past two decades.

Honey is a precious natural product that is marketed with a wide range of nutritional and medicinal properties. However, it is also a product subjected to frequent adulteration through mislabeling and mixing with cheaper and lower-quality honeys and various sugar syrups. In that sense, honey authentication regarding its genuine botanical and geographical origins, as well as the detection of any adulteration, is essential in order to protect consumer health and to avoid competition that could create a destabilized market. Various analytical techniques have been developed to detect adulterations in honey, including measuring the ratios of stable isotopes (mostly (13)C/(12)C) and the use of different spectroscopic, chromatographic, and electrochemical methods. This review aims to provide a cross-section of contemporary analytical methods used for the determination of honey authenticity in order to help the scientific community engaged in the field of honey chemistry make appropriate choices and select the best applications that should lead to improvements in the detection and elimination of fraudulent practices in honey manufacturing.

Honey is a complex mixture of various substances, and its composition depends on both botanical and geographical origin, as well as anthropogenic factors. The accurate identification of honey origin guarantees the satisfaction of consumers' needs and has an impact on the honey market value. Physicochemical parameters, some of which are used in routine analysis of honey quality, could be useful for the assessment of its origin. In this review, special attention is paid to those studies that assessed the sugar and mineral composition of honey, whether they were investigated in terms of botanical or geographical origin, or for the characterization of honey type. The oligosaccharides present in honey and the electrical conductivity of honey correlate strongly with its botanical origin. Mineral content could be indicative for distinguishing honeys according to their botanical and geographical origins because it depends on both the soil composition and the floral type of melliferous plants. This review provides insight into the results obtained by various studies from approximately the last 10 years concerning the sugar profile and the mineral and trace element content of different types of honey. An attempt was made to statistically analyze the results regarding mineral and trace element content in order to identify indicators that could distinguish honey by origin.

There is widespread concern about the high prevalence of vitamin D deficiency amid evidence to support that such a state may increase the risk of a wide range of adverse health outcomes. Estimating the prevalence of deficiency, as well as establishing links to health outcomes, requires the accurate and precise measurement of 25-hydroxyvitamin D [25(OH)D] in serum or plasma. Accurate measurement of 25(OH)D underlies the definitions of vitamin D deficiency, insufficiency, and sufficiency and, thus, prevalence estimates. Imprecise measurement of 25(OH)D in epidemiological research can result in incorrect null findings of associations with disease. When associations with disease are found, the inaccuracy of measurement forestalls defining the absolute level of 25(OH)D that is associated with increased risk. For the clinician, both inaccuracy and imprecision are problematic, because clinical care is most often based on a single measurement to define vitamin D status. New initiatives to develop a standard reference method and the assignment of &#x201C;true&#x201D; values to samples provide a solution to these problems. The use of standardized assays in large population studies will allow comparisons to be made between populations and over time that have not previously been possible and will improve our understanding of the role of vitamin D in health and disease.

Recent studies suggest that the concentration and genotype of vitamin D binding protein (VDBP) are important factors that determine the bioavailability of 25-hydroxyvitamin D [25(OH)D] in blood. Accumulating data indicate that, e.g., in pregnant women, hemodialysis patients, chronic kidney disease, liver failure, and bladder and pancreatic cancers, the measurement of free 25(OH)D in serum provides more relevant diagnostic information than measurement of total 25(OH)D. The aim of this study was to develop and validate an ELISA for direct measurement of free 25(OH)D in serum. A simple and direct ELISA was developed, based on a two-step immunoassay procedure performed in a microtiter plate. The assay has been characterized in terms of precision (4&#x2013;10% CV, according to concentration), sensitivity (limits of blank = 0.5&#x2013;1.0 pg/mL and LODs = 1.3&#x2013;1.8 pg/mL), accuracy (correlation to dialysis, ELISA = 0.99xdialysis-0.5 pg/mL, r² = 0.74), cross-reactivity of the antibody for the D₂ form (77%), and addition of both VDBP and albumin (35&#x2013;38% recovery upon addition of VDBP, 53&#x2013;58% upon addition of albumin). The assay has already been used in multiple studies, including its comparison with calculation methods and in studies of patients with liver failure, different ethnic groups, supplemented mice, respiratory diseases, and obesity. The free 25(OH)D ELISA can be used in studies as a valuable tool to establish the clinical relevance of free 25(OH)D.

Vitamin D is an important nutrient for many areas of human health and well-being, including improved bone strength, muscle movement, cognitive function, and immune health. The National Institute of Standards and Technology, in collaboration with the National Institutes of Health Office of Dietary Supplements, has developed SRM 3532 Calcium-Containing Solid Oral Dosage Form to help address the analytical challenges seen by the dietary supplement communities for the determination of vitamin D₃ (cholecalciferol) and elements. Described here is the process to assess the homogeneity and stability of the material, as well as the value assignment of the vitamin D₃ levels.

The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D [(25(OH)D] level &#x003C;50 nM, is unclear. Intramuscular (IM) injection of a large bolus of vitamin D (&#x2265;100 000 IU) is used, but its safety is uncertain. In 10 adults given an IM injection of 600 000IU vitamin D₃, we measured at baseline and at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D₃, 25(OH)D₃, 25(OH)D₂, total 25(OH)D, 3-epi-25(OH)D₃, and 24,25-dihydroxyvitamin D₃ [24,25(OH)₂D₃] using a standardized LC with tandem MS (MS/MS) assay; serum levels of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks. All participants had baseline total 25(OH)D levels &#x003E;50 nM. Serum 25(OH)D levels increased at 3, 4, and 24 weeks postinjection, peaking at 4 week.

Change in electrical conductivity is considered a potential indicator for the on-line monitoring of wine aging accelerated by ultrasound, as determined in our previous study; however, the exact mechanism of change is currently unclear. In this study, the ion content and the total ionic strength were analyzed by ion-exchange chromatography to investigate the change mechanism of the electrical conductivity of wine under ultrasound irradiation. The results indicate that the changes in wine electrical conductivity during ultrasound treatment correlate with the changes in the cations (Na(+), K(+), Ca(2+), Mg(2+), and NH₄(+)) and in the anions from the organic acids (malic acid, citric acid, tartaric acid, oxalic acid, and formic acid) and inorganic acids (Cl(-), SO₄(2-), and PO₄(3-)), especially for the ionic strength of the wine. Overall, electrical conductivity may be used to reflect the chemical reactions related to wine aging to a certain extent because the reactions can be initiated by the conversion of cations and by the degradation or auxiliary function of organic acids.

Previous studies have assessed vitamin D status based on the 25-hydroxyvitamin D [25(OH)D] concentration measured in samples from dried blood spots (DBSs). In 40 individuals participating in a clinical study, we compared 25(OH)D levels measured from DBSs and in serum using an LC-MS/MS reference procedure in collaboration with the Vitamin D Standardization Program. The main objective was to simplify and optimize current methods to produce an assay that can be used as a screening tool for 25(OH)D concentration assessment without derivatization. The DBS 25(OH)D levels, compared to serum concentrations, were found to have 101% accuracy overall, and the correlation coefficient (r) was 0.83 (P < 0.0001), with a significant linear relationship. Free 25(OH)D and vitamin D binding protein (VDBP) were assessed in the serum samples for potential correlations to the DBS calculations: the levels of free 25(OH)D had moderate to strong correlation to DBS and serum concentrations, with r values of 0.67 (P < 0.0001) and 0.76 (P < 0.0001), respectively. VDBP and hematocrit had no significant correlation to either DBS or serum sample types, with r values <0.1. In conclusion, the use of two DBSs and an increase in DBS sample size improved overall sample representation without the need for derivatization, and produced an accurate and robust method that can be used to screen 25(OH)D levels.

The 25-hydroxylated metabolite of vitamin D is the best clinical indicator of vitamin D status. For many years, emphasis has been on measuring total levels of 25-hydroxyvitamin D [25(OH)D], but recently, interest in measuring free 25(OH)D as a potentially better marker of vitamin D status has arisen. Since the 1980s when the first measurements of free 25(OH)D were made, little progress has been made in the development of rapid, reliable methods to determine the levels of free 25(OH)D. For many years, assessment of free 25(OH)D relied on calculations using levels of total 25(OH)D, albumin, and vitamin D binding protein (VDBP), for which many assays exist. However, because of vagaries in the measurement of VDBP in particular and the assumption of a constant affinity of VDBP for the vitamin D metabolites (which has been shown to be problematic), calculated values have proved suspect. This changed a few years ago when a new immunoassay was developed to measure free 25(OH)D directly. This review examines methods for determining free 25(OH)D, the different methods used in clinical studies, and the relationships between free 25(OH)D and other vitamin D metabolites and the physiologic functions affected by vitamin D metabolites, such as bone cell activity and turnover. The review also comments on the value of assessing free 25(OH)D and the efforts to standardize the assays.

A method using high-performance anion-exchange chromatography (HPAEC) with a pulsed amperometric detector (PAD) for thedetermination of mono- and disaccharides is described. The method was accepted by the International Dairy Federation and the Internal Organization for Standardization as a new work item for the determination of sugars in dairy matrixes, and the Milk and Milk Products technical committee of ISO/TC 34/SC 5 accepted the topic &#x201C;Milk and milk products &#x2013; Determination of the sugar contents &#x2013; High-performance anion-exchange chromatographic method (HPAEC&#x2013;PAD)&#x201D; as a new work item. The proposed method consists of an aqueous ethanol extraction of the sugars in the dairy sample, followed by clarification with Carrez I and II reagents. The clarified filtrate is diluted and then directly introduced in the HPAEC&#x2013;PAD system for quantification of the sugars. A single-laboratory validation of the proposed method has been scheduled for spring 2017.