Liquid chromatographic method to follow-up ceftazidime and pyridine in portable elastomeric infusion pumps over 24 h

Portable infusion pumps are an interesting solution to continue outpatient parenteral antimicrobial therapy (OPAT) at the patient's home. However, the use of ceftazidime for such applications is challenging in view of its relatively poor stability in solution. In this study, elastomeric infusion pumps with 6 or 7 g of ceftazidime were deflated over 24 h in an oven at 33°C while ceftazidime and its degradation product, pyridine, were regularly monitored. Hereto, a fast and sensitive liquid chromatographic (LC) method has been developed using a Kinetex^® C18 (150 × 3 mm, 2.6 μm) column with gradient elution. Ammonium formate 20 mM and acetonitrile (ACN) were mixed in a ratio of 98:2 v/v for mobile phase A and 85:15 v/v for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was set at 0.4 mL/min. The solution with a starting dose of 6 g ceftazidime was found to be degraded 10% after an average of 19 h 11 min so that an administration of 6 g to the patient was not reached. For the solution with a starting dose of 7 g of ceftazidime, 10% degradation was observed after an average of 18 h 42 min. However, by starting from a higher dose, an average of 6.56 g of ceftazidime could be administered over 24 h. In addition, 1.0% of pyridine versus ceftazidime pentahydrate with sodium carbonate (=mixture for injection) was formed over 24 h.     

Synthesis,Reactions, and Characterization of 6-Amino-4-(Benzo[b]Thiophen-2-YL)-2-Thioxo-1, 2-Dihydropyridine-3, 5-Dicarbonitrile

Abstract

Benzothiophene -2- carbaldehyde 1 reacted with 2-cyanoethanethioamide 2 in 1:2 molar ratios to give the corresponding 6-amino-4-(benzo[b]thiophen-2-yl)-2-thioxo-1, 2-dihydropyridine-3,5-dicarbonitrile 6. The synthetic potentiality of compound 6 was investigated via its reaction with active halogen-containing reagents to afford the corresponding thieno[2,3-b]pyridine derivatives 11a,b, 14, 16, and 19. Also, compound 6 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 21. Compound 21 condensed with 4-(2-thienyl)benzaldehyde to afford pyrazolo[3,4-b]pyridine derivative 23. Structural elucidation of all the newly synthesized heterocyclic compounds was based on elemental analyses, IR, ¹H NMR, and mass spectra.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Spectrophotometric Determination of Ceftazidime in Pharmaceutical Preparations Using Neocuproin as a Complexing Agent

Abstract

A simple and reproducible spectrophotometric method for the assay of ceftazidime with neocuproin-copper(II) reagent has been developed. The procedure is based on the drug in an acidic medium, subsequent formation of yellow ternary complex in citrate buffer solution (pH 4.2), and measurement at 454 nm. Beer's law is obeyed in the range 15.0–40.0 µg mL^?1 with correlation coefficient r ² = 0.9995. The procedure holds good accuracy and precision when applied to the analysis of ceftazidime in powder for injection with good recovery percent ranging from 100.17±1.0 without interference from additives.     

Synthesis,crystal structure and catalytic performance of bis (imino)pyridyl nickel complexes

Two new Ni(II) complexes of 2,6-bis[1-(2,6-diethylphenylimino)ethyl]pyridine (L¹), 2,6-bis[1-(4-methylphenylimino)ethyl]pyridine (L² ) have been synthesized and structurally characterized. Complex Ni(L¹)Cl₂?·?CH₃CN (1), exhibits a distorted trigonal bipyramidal geometry, whereas complex Ni(L¹)(CH₃CN)Cl₂ (2), is six-coordinate with a geometry that can best be described as distorted octahedral. The catalytic activities of complexes 1, 2, Ni{2,6-bis[1-(2,6-diisopropyl-phenylimino)ethyl]pyridine} Cl₂?·?CH₃CN (3), and Ni{2,6-bis[1-(2,6-dimethylphenylimino) ethyl]pyridine}Cl₂?·?CH₃CN (4), for ethylene polymerization were studied under activation with MAO.     

Synthesis, Conformational Studies and Inclusion Properties of Tetrakis[(2-pyridylmethyl)oxy]thiacalix[4]arenes

An attempted O-alkylation of the flexible macrocycle 1with 2-(chloromethyl)pyridine in the presence of Cs₂CO₃ under THF reflux afforded a mixture of twoconformers of tetra-O-alkylated product 4a in a ratio of 91:9 (cone-4a:1,2-alternate-4a)in 70% yield, while other possible isomers were not observed. In the case of Na₂CO₃, there was no reaction product,only the starting compound 1, whereasonly monoalkylated compound 3 was obtained when usingK₂CO₃ as the base. The distribution of cone conformer decreased in the case of O-alkylation of tetraol 1with 4-(chloromethyl)pyridine or benzyl bromide in the presence of Cs₂CO₃ in comparison with that ofO-alkylation with 2-(chloromethyl)pyridine, while the 1,2-alternate conformer increased in the same sequence. The larger Cs⁺might increase the contribution of the metal template effect, which can hold the 2-pyridylmethyl group(s) and theoxide group(s) on the same side of the tetrathiacalix[4]arene 1 through the cation-O^- and -N-interaction in the caseof O-alkylation of tetraol 1 with 2-(chloromethyl)pyridine.Only when the template metal can hold the 2-pyridyl group(s) andthe oxide group(s) on the same side of the tetrathiacalix[4]arene is the conformation immobilized to thecone. The template effect of the cesium cation plays an important role in this alkylation reaction. The structuralcharacterization of these products is also discussed.The two-phase solvent extraction data indicated thattetrakis[(2-pyridylmethyl)oxy]thiacalix[4]arenes 4a show strong Ag⁺ affinity and a high Ag⁺ selectivity wasobserved for cone-4a. A good Job plot proves 1:1 coordination of cone-4a with Ag⁺ cation.¹H-NMR titration of cone-4a with AgSO₃CF₃ also clearly demonstrates that a 1:1complex is formed with retention of the original symmetry. In contrast, the 1,2-alternate-4a can form a 2:1 metal/thiacalix[4]arene complex and the two metal-binding sites display positive allostericity. The conformational changes ofpyridine moiety from the original outward orientation of the ring nitrogen to the inside orientation toward thethiacalixarene cavity were observed in the processof Ag⁺ complexation.     

SPECTROPHOTOMETRIC STUDY OF COMPLEX FORMATION BETWEEN SOME ALKALI AND ALKALINE EARTH CATIONS AND SEVERAL CONVENTIONAL (N,N), (N,O) AND (O,O) LIGANDS IN 95% ETHANOL

Abstract

The complexation of Li⁺, Na⁺, Mg²⁺ and Ca²⁺ with 1,10-phenanthroline, 2,2′-bipyridine, 1,2-phenylenediamine, 2-aminopyridine, 8-hydroxyquinoline, catechol and ethylene glycol was studied in 95% ethanol by means of a competitive spectrophotometric method using murexide as indicator. Formation constants of 1:1 conplexes were determined. In the case of all ligands used, the stability of the complexes was found to vary in the order Mg²⁺ > Ca²⁺ > Li⁺ > Na⁺. It was found that the structure influences the formation and stability of resulting complexes. Effects of various parameters on complexation are discussed.     

Syntheses,spectroscopic characterization,thermal behavior,electrochemistry and crystal structures of two novel pyridine metatungstates

Two novel metatungstate compounds [Hdmpy]₄H₂[H₂W₁₂O₄₀]·4H₂O (dmpy?=?2,6-dimethyl pyridine) (1) and [Hpy]₄H₂[H₂W₁₂O₄₀] (py?=?pyridine) (2) have been synthesized by rational reaction, rather than hydrothermal or electrosynthetic reaction, of sodium tungstate dihydrate with 2,6-dimethyl pyridine and pyridine, respectively and characterized by IR and electronic spectroscopies, thermal behavior and electrochemistry. X-ray single-crystal structural analyses indicate that both structures consist of close-packed arrangements of the almost spherical Keggin-type anion [H₂W₁₂O₄₀]^6? with protonated 2,6-dimethyl pyridine or pyridine molecules filling the gap of the polyanions and interacting with the metatungstate anions in the mode of W-O···H-N or W-O···H-C, giving a two-dimensional network structure. The TG-DTA curves of 1 show that weight loss is divided into two stages, and reveal that the framework of the polyanion in 1 begins to decompose at 613°C. Electrochemical study shows that Compound 1 exhibits two chemically quasi-reversible one-electron reduction processes in aqueous solution (0.5?M NaCl?+?HCl) in the pH range 4–7.     

A Stability Indicating HPLC Assay for Prednisolone Sodium Phosphate in Implantable Infusion Pumps

Abstract

A stability indicting assay for prednisolone sodium phosphate (PSP) in solutions for implantable infusion pumps was developed. PSP and its major breakdown product, prednisolone, were separated from formulation excipients by reverse phase chromatography on a phenyl-bonded phase column using an acetonitrile-phosphate buffer mobile phase. Detection was by ultraviolet absorbance at 243 mm. Recovery from a synthetic formulation was 101.0 ± 0.4% (n=6). The method was used to monitor the stability of PSP solutions in implantable infusion pumps maintained at 37°C over a 21 day period.     

Colorimetric Determination of Propofol in Bulk form,Dosage Form and Biological Fluids

ABSTRACT

Propofol is coupled with 2, 6-dichloroquinone-4-chlorimide (DCQ) in a reaction buffered at pH 9.6 to give a colored product having an analytically useful maximum at 635 nm. The factors affecting the color generation were optimized and incorporated in the procedure. The reacted propofol has a molar absorptivity of 3.9 × 10^?4 L mol^?1 cm^?1, and Beer's law is obeyed for concentrations 1-5 μg ml^?1 with detection limit 0.25 μg ml^?1. The method was found applicable to biological fluids (plasma and urine) spiked with propofol at concentration levels 1-5 μg ml^?1 for plasma and 1-5 μg 0.5 ml^?1 urine (less sensitivity is obtained with urine volumes above 0.5 ml) with detection limits 0.28 μg ml^?1 for plasma and 0.4 μg 0.5 ml^?1 urine. The average recovery for the commercial preparation (1% w/v propofol emulsion intravenous injection for infusion) was 99.54% with an RSD of 1.05%. The method was validated by an adopted HPLC method. The results obtained by the HPLC method for the commercial preparation were statistically compared with the proposed method and evaluated at the 95% confidence limits.     

2-Phenyl-1-boraadamantane complexes. Synthesis and intramolecular dynamics

The reaction of triallylborane with 3-phenylprop-1-yne at 135–140 °C followed by treatment of the reaction mixture with MeOH afforded 7-benzyl-3-methoxy-3-borabicyclo[3.3.1]non-6-ene (1) in 81% yield. Hydroboration of compound1 with a solution of BH₃ in THF yielded the tetrahydrofuran complex of 2-phenyl-1-boraadamantane (2). The reactions of trimethylamine or pyridine with compound2 afforded the trimethylamine (3) or pyridine (4) complexes of 2-phenyl-1-boraadamantane. respectively. Hindered rotation about the C(2)−Ph bond in adduct3 was observed by¹H and¹³C NMR spectroscopy. The activation energy of this process is 58.6 kJ mol⁻¹ (determined by 2D¹H−¹H EXSY spectroscopy).     

Thermodynamic Dissociation Constants for [MPy4(NO3)2]*2Py Clathrates (M=Mn,Co, Ni,Cu)

Abstract

Stoichiometry and thermodynamic parameters of the title clathrates dissociation have been studied with thermoanalytical and strain method techniques. The [MPy₄(NO₃)₂]^*2Py (M = Mn, Co, Ni) clathrates dissociate with collapsing clathrate porous phase and destruction of the host complex to give the respective tripyridine complexes and gaseous pyridine. The [CuPy₄(NO₃)₂]^*2Py dissociates with collapsing clathrate phase but giving the host [CuPy₄(NO₃)₂] complex as individual phase, with the tripyridine complex forming in further course of decomposition. The comparison of the thermodynamic dissociation parameters for the [MPy₄(NO₃)₂]^*2Py series with M = Mn, Co, Ni, Cu, Zn and Cd shows that the differences in the stability of the compounds do not correlate with structural parameters of the clathrates but depend on the nature of the metal cation in the host complex. Thermodynamic stability of these clathrate phases follows the general sequence of stabilty for complexes of the 3d transition metals known as Irwing-Williams sequence: Mn<Fe<Co<Ni<Cu>Zn. These results disclose the main issue of instability of the [MPy₄(NO₃)₂]^*2Py clathrates as instability of the respective host complexes.     

Intermolecular interactions of tetraphenyl-porphyrin and its pyridine metallocomplexes in the crystalline state

Crystalline solvates of synthetic tetraphenylporphyrin and its pyridinie metallocomplexes (Zn²⁺, Cu²⁺, Ni²⁺, Co²⁺, Mn³⁺, Fe³⁺) have been studied by thermogravimetric analysis. A comparative analysis of our thermochemical data and the literature XRD data was carried out for the pyridine complexes of metallotetraphenylporphyrins. It was found that the energy stability and structural characteristics of the pyridine complexes of metallotetraphenylporphyrins depended on the nature of the central metal ion. The pyridine complexes are stabilized by the direct metal porphyrin π-dative macrocycle interaction and the increased residual positive charge on the central metal ion. The activation energies of thermal destruction of the pyridine complexes of metallotetraphenylporphyrins vary from 230 kJ·mol⁻¹ to 330 kJ·mol⁻¹, which is suggestive of the high kinetic stability of the complexes. For the molecular complexes under study, the limiting stage of destruction was found to be the chemical reaction itself, and the kinetic characteristics demonstrated the compensation effect, indicative of the similar mechanism of thermooxidative destruction of the pyridine complexes of metallotetraphenylporphyrins.     

Pentacoordinated iridium(I) complexes incorporating azopyridine chelation. Synthesis,structure and bonding

The reaction of [Ir(COD)Cl]₂ with 2-(arylazo)pyridine (L) in dichloromethane solution has afforded the nonelectrolytic pentacoordinated species of type Ir(L)(COD)(Cl) from which the corresponding bromides and iodides have been synthesised by metathesis (COD=1,5-cyclooctadiene). L ligands used are: 2-(phenylazo)pyridine (L¹); 2-(m-tolylazo)pyridine (L²) and 2-(p-chlorophenylazo)pyridine (L³). The X-ray structures of Ir(L²)(COD)(Cl)·0.5 CH₂Cl₂ and Ir(L³)(COD)(I) have been determined revealing square-pyramidal geometry. The relatively short IrN(azo) lengths (∼2.00 Å) and the relatively long NN bond distance (∼1.30 Å) are consistent with significant dππ* (azo) back-bonding. The HOMO (50% Ir and 15% azo character) and LUMO (50% azo and 30% Ir character) are primarily localised in the IrL fragment and the absorption bands near 600 nm is assigned tentatively to the HOMO→LUMO transition. The stability of the pentacoordinated structures and the inertness to oxidative addition of the present complexes in contrast to the behaviour of corresponding 2,2′-bipyridine species (tetracoordinated, reactive) is rationalised in terms of π-acidity order L≫bpy.     

稀土-异烟酰肼席夫碱配合物的设计、合成与结构

由异烟酰肼和2-吡啶甲醛合成了席夫碱配体HL,并和稀土离子合成组装得一系列稀土配合物。用X-射线单晶衍射对配合物的结构进行了测定。通过荧光测试发现La配合物有荧光,而Eu,Dy则使配体的荧光淬灭。     

Speciation analysis of manganese in tea samples using flame atomic absorption spectrometry after cloud point extraction

The speciation of Mn(II) in tea infusion was studied using cloud point extraction (CPE). In tea infusion, the flavonoid-bound Mn(II) was extracted at pH 5.0 using Triton X-100 (TX-100), the remaining free aquated Mn(II) and weakly-complexed Mn(II) in solution were both chelated with 8-hydroxyquinoline (HOx) and CPE-preconcentrated with TX-100. The enriched analyte was determined by flame AAS. The optimal concentrations for CPE of 0.02 ppm Mn were as follows: TX-100, 0.2% (v/v); HOx, 1.0 × 10⁻⁴ M; NaCl, 1.0% (w/v). LOD was 1.9 μg/L with a preconcentration factor of 10–20. The method was validated using a standard XAD-resin separation procedure and applied to synthetic seawater and CRM samples.     

High-Pressure Liquid Chromatographic Analysis for Quantitation of BMY-28142 and Ceftazidime in Human and Rabbit Serum

Abstract

The quantitative measurement of BMY-28142 and ceftazidime in serum after protein precipitation were compared using a reverse-phase liquid chromatographic (LC) method. Detection using ultraviolet absorbance at 275 nm gave a sensitivity of 1.0 mcg/ml and 1.5 mcg/ml for BMY-28142 and ceftazidime respectively, and both gave linear response to concentration of at least 80 mcg/ml. Drug recovery after sample deproteination was 104% for BMY-28142 in rabbit serum and 93% in human serum. Results indicate a precise and accurate assay for this drug can be obtained using a simple LC method.     

Measurement of ceftazidime concentration in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry. Application to critically ill patients and patients with osteoarticular infections

Ceftazidime is an antibiotic belonging to the third generation of the cephalosporin family. It is indicated in the treatment of serious, simple or mixed bacterial infections, and its administration in continuous or intermittent infusion allows optimization of the concentration of antibiotic to keep it above the minimum inhibitory concentration. We developed and validated a chromatographic method by ultra‐performance liquid chromatography–tandem mass spectrometry to measure ceftazidime concentration in human plasma. Following extraction with acetonitrile and 1,2‐dichloroethane, the chromatographic separation was achieved using an Acquity ® UPLC ® BEH^TM (2.1 × 100 mm i.d., 1.7 µm) reverse‐phase C₁₈ column, with a water–acetonitrile linear gradient containing 0.1% formic acid at a 0.4 mL/min flow rate. Ceftazidime and its internal standard (cefotaxime) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass‐to‐charge transitions of 547.0 → 467.9/396.1 and 456.0 → 395.8/324.1, respectively. The limit of quantification was 0.58 mg/L and linearity was observed in the range 0.58–160 mg/L. Coefficients of variation and absolute relative biases were <9.8 and 8.4%. The mean recovery for ceftazidime was 74.4 ± 8.1%. Evaluation of the matrix effect showed ion enhancement, and no carry‐over was observed. The validated method could be applied to daily clinical laboratory practice to measure the concentration of ceftazidime in plasma. Copyright © 2015 John Wiley & Sons, Ltd.     

Determination of LY217332, A New 3'-Quaternary Ammonium Cephalosporin,In Plasma by Solid Phase Column Extraction and HPLC

Abstract

A sensitive and rapid assay has been developed for the determination of LY217332, a 3'-imidazolo[4,5-c]pyridinium cephalosporin, in plasma. The method utilizes cyano solid phase column extraction and HPLC with ultraviolet detection. The lower limit of detection is 5 ng/ml plasma and the relative standard deviation for precision and accuracy was 5% or less from 50–500 ng/ml. The method is applicable to the assay of ceftazidime, cephaloridine, cefpirome and BMY-28142 with minor modification of the mobile phase and the detection wavelength.     

A Simplified,One-Pot Preparation of Acetobromosugars from Reducing Sugars

ABSTRACT

Acetobromoglycoses continue to be important as glycosyl donors in the synthesis of simple glycosides as well as complex oligosaccharides. From reducing sugars they are usually prepared via their peracetates in two steps. In the first step, sugars are converted to their peracetates using pyridine and acetic anhydride^1,2 and the acetates are then converted in a second step to acetobromosugars using a solution of hydrogen bromide in glacial acetic acid(HBr/HOAc).² Although not in use very often Redemann and Niemann³ as well as Lemieux⁴ have described one-pot methods for the preparation of acetobromoglucose wherein the reducing sugar is first treated with acetic anhydride in the presence of sulfuric acid³ or perchloric acid⁴ respectively to afford the peracetate. Direct conversion of the peracetate to its 1-bromo-derivative, in yields ranging from 80-87%, was then achieved by either treating the solution of the peracetate with gaseous HBr³ or with bromine in the presence of red phosphorus.⁴ In another approach to a one-pot method Humoller⁵ prepared tri-O-acetyl-β-L-arabinopyranosyl bromide in 40% yield by passing anhydrous HBr gas through a suspension of L-arabinose in acetic anhydride. By an essentially similar method Dale⁶ obtained acetobromosugars in yields ranging from 26-77% depending upon the sugar. Because acetobromosugars are the compounds most frequently used for synthesizing numerous other sugar derivatives, we thought it would be worthwhile to report our recent observation that acetic anhydride and HBr/HOAc can be used with advantage for the preparation of acetobromosugars.     

The Synthesis,Crystal, Molecular and Electronic Structure of [ReCl2(NO)(py)3]

In line with our investigations of rhenium nitrosyl complexes, we have studied the reaction of [ReCl₃(NO)(OPPh₃)(PPh₃)] with pyridine. The [ReCl₂(NO)(py)₃] complex obtained in this reaction has been characterised by IR, electronic spectra and magnetochemical measurements; ligand field parameters and the electronic structure have been determined. The crystal and molecular structure of [ReCl₂(NO)(py)₃] has been solved by the heavy atom method. Crystals of [ReCl₂(NO)(py)₃] contain distorted octahedral molecules with the pyridine ligands in the mer-arrangement. The nitrosyl group is coordinated linearly to the rhenium atom as NO⁺.