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We analyze the structure, hydration, and pKavalues of p-guanidinoethyl-phenol througha combined experimental and theoretical study. These issues are relevantto understand the mechanism of action of the tetrameric form, theantibacterial compound tetra-p-guanidinoethyl-calix[4]arene(Cx1). The investigated system can also be useful to model other pharmaceuticaldrugs bearing a guanidine function in the vicinity of an ionizablegroup and the effect of arginine on the pKaof vicinal ionizable residues (in particular tyrosine) in peptides.The p-guanidinoethyl-phenol monomer (mCx1) has twoionizable groups. One important particularity of this system is thatit exhibits high molecular flexibility that potentially leads to enhancedstabilization in folded structures by direct, strong Coulombic interactionsbetween the ionizable groups. The first pKacorresponding to ionization of the −OH group has experimentallybeen shown to be only slightly different from usual values in substitutedphenols. However, because of short-range Coulombic interactions, therole of intramolecular interactions and solvation effects on the aciditiesof this compound is expected to be important and it has been analyzedhere on the basis of theoretical calculations. We use a discrete-continuumsolvation model together with quantum-mechanical calculations at theB3LYP level of theory and the extended 6-311+G(2df,2p) basis set.Both intra- and intermolecular effects are very large (∼70kcal/mol) but exhibit an almost perfect compensation, thus explainingthat the actual pKaof mCx1 is close tofree phenol. The same compensation of environmental effects appliesto the second pKathat concerns the guanidiniumgroup. Such a pKacould not be determinedexperimentally with standard titration techniques and in fact thetheoretical study predicts a value of 14.2, that is, one unit abovethe pKaof the parent ethyl-guanidiniummolecule. [ABSTRACT FROM AUTHOR]

Background: In severe infections, high-concentration vancomycin may be administered by continuous infusion. The dosage of vancomycin may reach 60 mg/kg per day., Objectives: To study the feasibility of preparing high-concentration vancomycin solutions (40 to 83.3 mg/mL), to study the effect of an electric syringe pump on the physical stability of high-concentration vancomycin, and to study the stability of vancomycin 62.5 and 83.3 mg/mL in 0.9% sodium chloride (0.9% NaCl) or 5% dextrose in water (D5W) with storage up to 48 h at room temperature., Methods: The following sets of syringes were prepared: (1) 4 syringes of vancomycin in 0.9% NaCl for each of 5 concentrations between 40 and 83.3 mg/mL (total 20 syringes); (2) 6 syringes at 83.3 mg/mL in 0.9% NaCl and 6 syringes at 83.3 mg/mL in D5W; and (3) 30 syringes at 83.3 mg/mL in D5W. Visual inspection was performed for all 3 syringe sets, and subvisual inspection for sets 1 and 2 (for periods of 24 h for set 1 and 48 h for sets 2 and 3). One syringe of vancomycin 83.3 mg/mL with each solvent was inserted into an electric syringe pump, and samples from the infusion line and collected after transit through the pump were inspected visually. Chemical stability was evaluated by high-performance liquid chromatography, and physical stability, pH, and osmolality were investigated., Results: For all sets of syringes, no physical modification was observed over time, nor were any changes observed after transit through the electric syringe pump. In 0.9% NaCl, vancomycin 62.5 and 83.3 mg/mL retained more than 90% of the initial concentration after 48 and 24 h, respectively; however, for the 83.3 mg/mL solution, precipitate was visible after 48 h. In D5W, vancomycin at 62.5 and 83.3 mg/mL retained more than 90% of the initial concentration after 48 h., Conclusion: It was feasible to prepare high-concentration solutions of vancomycin. The electric syringe pump did not cause any precipitation. Vancomycin in D5W at 62.5 and 83.3 mg/mL was stable over 48 h at room temperature. Precipitation occurred in 0.9% NaCl. D5W is therefore recommended as the solvent for this drug., Competing Interests: Competing interests: None declared., (2019 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Nitrogen and its numerous hydrogenated and oxygenated derivatives are of main importance in our environment and in living cells as well in both qualitative and quantitative aspects. Their monitoring is needed to evaluate all disturbances occurring in the nitrogen cycle and in pathophysiological events related to variations of nitric oxide (NO) bioavailability. Many analytical methods are devoted to the measurement of nitrogen species, especially those related to NO, in the environmental, biological and pharmacological fields, and they have already been compiled and discussed in numerous reviews. Nitrogen isotope ( 15 N) is stable and has a low level of natural abundance. Labeling nitrogen species with 15 N associated with mass spectrometry (MS) gives rise to more mechanistic information and improved analytical performances compared to conventional methods. The present review is dedicated to the 15 N labeling of related nitrogen species to monitor their interconversion and metabolism, the different chemical probes used for their derivatization and the corresponding separative methods coupled with MS for analyzing resulting adducts. The fragmentation mode of the different adducts and the resulting selectivity and sensitivity are discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)