ABSTRACT
An effective thin layer chromatography (TLC) purification procedure coupled to high-performance liquid chromatography (HPLC) method was developed for the determination of florfenicol (FF) in pig, chicken and fish feedstuffs. The feedstuff samples were extracted with ethyl acetate, defatted with n-hexane saturated with acetonitrile, and further purified by TLC. The chromatographic separation was performed on a Waters Symmetry C18 column using an isocratic procedure with acetonitrile-water (35:65, v/v) at 0.6mL/min. The ultraviolet (UV) detector was set at a wavelength of 225nm. The FF concentrations in feedstuff samples were quantified using a standard curve. Good linear correlations (y=159075x-15054, r>0.9999) were achieved within the concentration range of 0.05-200µg/mL. The recoveries of FF spiked at levels of 1, 100 and 1000µg/g ranged from 80.6% to 105.3% with the intra-day and inter-day relative standard deviation (RSD) less than 9.3%. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.02 and 0.06mg/kg for pig feedstuffs, 0.02 and 0.07mg/kg for chicken feedstuffs, and 0.02 and 0.05mg/kg for fish feedstuffs, respectively. This reliable, simple and cost-effective method could be applied to the routine monitoring of FF in animal feedstuffs.
Subject(s)
Animal Feed/analysis , Chromatography, High Pressure Liquid/methods , Chromatography, Thin Layer/methods , Thiamphenicol/analogs & derivatives , Limit of Detection , Linear Models , Reproducibility of Results , Thiamphenicol/analysis , Thiamphenicol/isolation & purificationABSTRACT
Neuromuscular blocking agents (NMBAs) are widely used in surgery to achieve skeleton muscles relaxation under light anesthesia status. In this work, we synthesized a series of 3,16-bisquaternary ammonium steroidal NMBAs. Among them, three compounds exhibited higher in vitro activities than the commenced drug rocuronium. In addition, structure-activity relationship was unveiled. We found that the intact acetylcholine-like moiety in D-ring was not necessary for maintaining activity but both the acetyl group and the quaternary nitrogen were very essential.
Subject(s)
Neuromuscular Blocking Agents/chemical synthesis , Neuromuscular Blocking Agents/pharmacology , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/pharmacology , Steroids/chemistry , Animals , Chemistry Techniques, Synthetic , Male , Mice , Neuromuscular Blocking Agents/chemistry , Quaternary Ammonium Compounds/chemistry , Structure-Activity RelationshipABSTRACT
A series of steroidal 3,16-bis-quaternary ammonium salts were synthesized and screened on mouse hemi-diaphragm to explore new steroidal neuromuscular blocking agents. There were two compounds, 3ß-piperidino derivate 8d (IC(50) = 3.49 µM) and 3ß-N-methylbenzylamino derivate 8g (IC(50) = 4.54 µM), showing activity close to rocuronium (IC(50) = 2.50 µM). The preliminary structure-activity relationship was deduced from the bioactivity results with the aid of the calculated N-N distance and log P. Meanwhile, the interactions between the ligand and binding pocket were revealed by docking 8d to the ligand binding domain of the mouse muscle nicotinic acetylcholine receptor (nAChR). This nAChR was modeled using Molecular Operating Environment (MOE) package indirectly from mollusca acetylcholine binding protein with mouse neuron α7 nAChR as intermediary template.
Subject(s)
Molecular Probes/pharmacology , Morpholines/pharmacology , Neuromuscular Blocking Agents/pharmacology , Quaternary Ammonium Compounds/pharmacology , Receptors, Nicotinic/metabolism , Steroids/pharmacology , Animals , Diaphragm/drug effects , Dose-Response Relationship, Drug , Ligands , Male , Mice , Molecular Probes/chemical synthesis , Molecular Probes/chemistry , Molecular Structure , Morpholines/chemical synthesis , Morpholines/chemistry , Muscle, Skeletal/drug effects , Neuromuscular Blocking Agents/chemical synthesis , Neuromuscular Blocking Agents/chemistry , Neurons/drug effects , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Steroids/chemical synthesis , Steroids/chemistry , Structure-Activity RelationshipABSTRACT
4alpha-Aminosteroids were synthesized by the substitution of a 2alpha-bromo ketone using K(2)CO(3) as an activator; 4beta-aminosteroids were synthesized in excellent yields by a highly regioselective and trans-stereospecific ring opening of a steroidal 3,4alpha-epoxide using ZnCl(2)-H(2)O as a catalyst.
Subject(s)
Androstanes/chemical synthesis , Steroids/chemical synthesis , Androstanes/chemistry , Catalysis , Ketones/chemistry , Steroids/chemistry , Zinc/chemistryABSTRACT
Thirteen new 5-cyclopropanespirohydantoins with various N-3 substituents were synthesized and their pharmacological activity was determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by maximal electroshock seizure (MES) test and subcutaneous pentylenetetrazole (scPTZ) test models in mice. All compounds substituted with cyclopropyl group at fifth position of hydantoin ring showed better protection against MES test. Compounds 5b, 5d, 5e, 5g and 5j were found to be the most potent compounds of this series and compared with the reference drug phenytoin sodium in MES test. Compound 5j also showed equipotent activity with the standard drug sodium valproate at the doses of 20 and 40 mg kg(-1) in scPTZ test.
Subject(s)
Anticonvulsants/chemical synthesis , Hydantoins/chemical synthesis , Animals , Anticonvulsants/pharmacology , Drug Evaluation, Preclinical , Hydantoins/pharmacology , Mice , Rats , Seizures/drug therapy , Seizures/prevention & control , Spiro Compounds , Structure-Activity RelationshipABSTRACT
Three hydrazone ligands, H2L1-H2L3, made from salicylaldehyde and ibuprofen- or naproxen-derived hydrazides, were prepared and transformed into the corresponding copper(II) complexes [Cu(II)L1] x H2O, [Cu(II)L2], and [(Cu(II))2(L3)2] x H2O x DMF (Scheme). The X-ray crystal structure of the last-mentioned complex was solved (Fig. 1), showing a square-planar complexation geometry, and the single units were found to form a one-dimensional chain structure (Fig. 2). The interactions of these complexes with CT-DNA were studied by different techniques, indicating that they all bind to DNA by classical and/or non-classical intercalation modes.
