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

Development and validation of a simple and sensitive size-exclusion chromatography method for quantitative determination of heparin in pharmaceuticals

Heparin is widely used as an anticoagulant for the treatment and prevention of various thrombotic diseases. However, due to its high anionic charge, heterogeneity in size distribution and high polarity, its analysis is very challenging. In this paper, a novel method based on size-exclusion chromatography (SEC) for quantitative determination of intact heparin in pharmaceuticals is presented. Analyses were performed on a BioSep-SEC-S 2000 column with L-arginine solution at pH 6.5 as mobile phase and UV detection at 210 nm. The proposed method was found to be selective, linear (R2 > 0.997) over the concentration range of 3.1 to 1222 µg mL–1, with a limit of detection of 1.0 µg mL–1. Intra-day and inter-day precision were below 5.1 % and inaccuracy expressed as bias did not exceed 6.5 %. The reported method is simple, selective, sensitive, and requires no laborious sample preparation, which makes it appropriate for routine quantitative analysis of heparin in pharmaceuticals

Koncentracije zdravilnih učinkovin v slovenskih komunalnih in bolnišničnih odpadnih vodah: preliminarna raziskava

Pharmaceuticals in wastewater have clearly raised concern and a broad range of analytical methods has been used to assess the risk as accurately as possible. The aim of our study was to measure and compare the concentrations of atorvastatin, bisoprolol, carbamazepine, ciprofloxacin, clofibric acid, diclofenac, fluoxetine, metoprolol, and sertraline in wastewater samples taken from one municipal and one hospital wastewater treatment plant in Slovenia and to predict the potential environmental burden using the risk quotient. In both effluents only clofibric acid and fluoxetine were not detected. The measured concentrations of the remaining seven pharmaceuticals varied between the ng L-1 and the μg L-1 range. Hospital effluent showed higher concentrations, except for diclofenac and carbamazepine. However, high risk quotient was found only for ciprofloxacin and diclofenac in both municipal and hospital effluent. In conclusion, our method can provide a useful tool for systematic monitoring of pharmaceuticals commonly found in wastewater, which will enable a reliable assessment of the risks for the aquatic biota and humans. Knowing the risks will help to plan wastewater treatment and preserve our environment.Koncentracije zdravilnih učinkovin v slovenskih komunalnih in bolnišničnih odpadnih vodah: preliminarna raziskava. Pojavljanje ostankov zdravilnih učinkovin v odpadnih vodah postaja vedno bolj aktualna tematika in posledično se širi nabor analiznih metod, ki omogočajo natančno ugotavljanje njihove prisotnosti in služijo kot orodje za napovedovanje tveganja teh onesnažil v vodnem okolju. Namen naše raziskave je bil kvantitativno ovrednotiti prisotnost izbranih zdravilnih učinkovin (atorvastatin, bisoprolol, ciprofloksacin, diklofenak, fluoksetin karbamazepin, klofibrinska kislina, metoprolol in sertralin) na iztoku ene komunalne in ene bolnišnične čistilne naprave. Na osnovi meritev koncentracij smo z uporabo količnika tveganja ocenili okoljsko breme vključenih spojin. Ugotovili smo prisotnost sedmih zdravilnih učinkovin, medtem ko klofibrinske kisline in fluoksetina nismo zaznali v nobenem vzorcu. Izmerjene koncentracije so bile v širokem koncentracijskem območju (od ng L-1 do μg L-1), praviloma višje v bolnišnični odpadni vodi, z izjemo diklofenaka in karbamazepina. Izračunan količnik tveganja nakazuje na visoko tveganje za ciprofloksacin in diklofenak v vseh analiziranih vzorcih odpadnih voda. Raziskava je pokazala, da je razvita metoda primerno orodje za nadaljnje študije, ki bodo na podlagi sistematičnega spremljanja teh novodobnih onesnažil v odpadnih vodah omogočile zanesljivejšo oceno tveganja za izpostavljene vodne organizme in tudi za zdravje ljudi. Poznavanje teh tveganj bo prispevalo k načrtovanju ustrezne tehnologije čiščenja odpadnih voda in posledično k ohranjanju čistega in zdravega okolja

Evaluation of the stability of hydrocortisone sodium succinate in solutions for parenteral use by a validated HPLC-UV method

This study aimed to determine the in-use stability (t95%) of hydrocortisone sodium succinate (HSS) infusion solutions and provide evidence-based guidelines on their usability. HSS infusion solutions were prepared and stored as recommended by the manufacturer and under common conditions in our hospital. The effects of HSS concentration (1 and 4 mg/mL), solvent (isotonic saline and glucose), temperature (ambient and 30°C), and light on its stability were evaluated using a validated stability-indicating HPLC-UV method. HSS degradation followed first-order kinetics. No significant difference in its stability was observed between the two evaluated concentrations, solvents and light exposure (t95% between 25 and 30 h). Elevated temperature (30°C) affected HSS stability and significantly reduced the t95% (4.6-6.3 h). HSS infusion solutions are physically and chemically stable (˂5% degradation) for at least 6 h if stored below 30°C. The in-use stability may be extended up to 24 h if stored below 24°C

Gas Metallicities in the Extended Disks of NGC 1512 and NGC 3621. Chemical Signatures of Metal Mixing or Enriched Gas Accretion?

(Abridged) We have obtained spectra of 135 HII regions located in the inner and extended disks of the spiral galaxies NGC 1512 and NGC 3621, spanning the range of galactocentric distances 0.2-2 x R25 (from 2-3 kpc to 18-25 kpc). We find that the excitation properties of nebulae in the outer (R>R25) disks are similar to those of the inner disks, but on average younger HII regions tend to be selected in the bright inner disks. Reddening by dust is not negligible in the outer disks, and subject to significant large-scale spatial variations. For both galaxies the radial abundance gradient flattens to a constant value outside of the isophotal radius. The outer disk O/H abundance ratio is highly homogeneous, with a scatter of only ~0.06 dex. Based on the excitation and chemical (N/O ratio) analysis we find no compelling evidence for variations in the upper initial mass function of the ionizing clusters of extended disks. The O/H abundance in the outer disks of the target galaxies corresponds to 35% of the solar value (or higher, depending on the metallicity diagnostic). This conflicts with the notion that metallicities in extended disks of spiral galaxies are necessarily low. The observed metal enrichment cannot be produced with the current level of star formation. We discuss the possibility that metal transport mechanisms from the inner disks lead to metal pollution of the outer disks. Gas accretion from the intergalactic medium, enriched by outflows, offers an alternative solution.Comment: Accepted for publication in the Astrophysical Journa

HII Region Metallicity Distribution in the Milky Way Disk

The distribution of metals in the Galaxy provides important information about galaxy formation and evolution. HII regions are the most luminous objects in the Milky Way at mid-infrared to radio wavelengths and can be seen across the entire Galactic disk. We used the NRAO Green Bank Telescope (GBT) to measure radio recombination line and continuum emission in 81 Galactic HII regions. We calculated LTE electron temperatures using these data. In thermal equilibrium metal abundances are expected to set the nebular electron temperature with high abundances producing low temperatures. Our HII region distribution covers a large range of Galactocentric radius (5 to 22 kpc) and samples the Galactic azimuth range 330 degree to 60 degree. Using our highest quality data (72 objects) we derived an O/H Galactocentric radial gradient of -0.0383 +/- 0.0074 dex/kpc. Combining these data with a similar survey made with the NRAO 140 Foot telescope we get a radial gradient of -0.0446 +/- 0.0049 dex/kpc for this larger sample of 133 nebulae. The data are well fit by a linear model and no discontinuities are detected. Dividing our sample into three Galactic azimuth regions produced significantly different radial gradients that range from -0.03 to -0.07 dex/kpc. These inhomogeneities suggest that metals are not well mixed at a given radius. We stress the importance of homogeneous samples to reduce the confusion of comparing data sets with different systematics. Galactic chemical evolution models typically derive chemical evolution along only the radial dimension with time. Future models should consider azimuthal evolution as well.Comment: Accepted for publication in Ap

Določanje benzodiazepinov v urinu preko benzofenonskih derivatov z uporabo tekočinske kromatografije sklopljene s tandemsko masno spektrometrijo

The aim of this study was to validate a new method for determining benzodiazepines in urine via their benzophenone derivatives, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were analysed after acid hydrolysis of urine and extraction by ethyl acetate in the presence of an internal standard. Samples were analysed using electrospray ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic run time on a reversed phase C18 analytical column was set for 9 min. This method was validated in 21 patients receiving methadone. Benzodiazepines intake was established in two out of three patients. LC-MS/MS results were also compared with the rapid immunoassay and the methods showed good agreement. However, in three cases benzodiazepines were detected by LC-MS/MS, but not by the immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or even higher than of previously reported methods, which makes it suitable as a confi rmatory method.Razvili smo selektivno in občutljivo metodo za določanje nekaterih benzodiazepinov v urinu preko določanja njihovih benzofenonov. Metoda temelji na tekočinski kromatografi ji, sklopljeni s tandemsko masno spektrometrijo (LC-MS/MS). Izbrane benzodiazepine smo analizirali po kisli hidrolizi urinskih vzorcev in ekstrakciji z etilacetatom v prisotnosti internega standarda. Vzorce smo analizirali z elektrorazprševalno ionizacijo z MRM načinom detekcije. Čas kromatografske ločbe na reverznofazni (C18) analitski koloni je bil 9 min. Metoda je bila validirana in preizkušena na 21 pacientih, ki so prejemali metadonsko terapijo. Pri dveh tretjinah primerov je bil vnos benzodiazepinov tudi potrjen. Vzorce smo testirali tudi s hitro imunokemijsko metodo in rezultate primerjali z rezultati pridobljenimi z LC-MS/MS metodo. Ugotovili smo dobro ujemanje med rezultati pridobljenimi z obe a metodama. Kljub temu smo v treh primerih določili prisotnost benzodiazepinov z LC-MS/MS metodo, ki je z imunokemijsko metodo nismo. Občutljivost razvite metode je primerljiva ali celo boljša od predhodno opisanih metod, zato jo lahko uporabimo kot potrditveno metodo