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Analytical Sciences : the International... Jun 2019Molecularly imprinted polymers (MIPs) for promazine (PZ) and chlorpromazine (CPZ), MIP and MIP, were prepared by multi-step swelling and polymerization using methacrylic...
Preparation and Evaluation of Molecularly Imprinted Polymers for Promazine and Chlorpromazine by Multi-step Swelling and Polymerization: the Application for the Determination of Promazine in Rat Serum by Column-switching LC.
Molecularly imprinted polymers (MIPs) for promazine (PZ) and chlorpromazine (CPZ), MIP and MIP, were prepared by multi-step swelling and polymerization using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a crosslinker. The retention and molecular-recognition properties of MIP and MIP were evaluated using a mixture of potassium phosphate buffer and acetonitrile, or a mixture of ammonium formate and acetonitrile as the mobile phase in LC. PZ and CPZ gave the maximal retentions on MIP and MIP at an apparent pH 8.2 using a mixture of potassium phosphate buffer and acetonitrile as the mobile phase. The retentions of PZ and CPZ decreased with an increase of acetonitrile contents from 70 to 90 vol% using a mixture of ammonium formate and acetonitrile as the mobile phase. The template molecules (PZ and CPZ, respectively) were recognized the most on the respective MIPs, and the imprinting factor of PZ was higher on MIP than on MIP. These results indicate that in addition to shape recognition, ionic and hydrophobic interactions seem to work for the retention and molecular-recognition of PZ and CPZ on the MIPs. MIP was successfully utilized for the selective extraction of PZ in rat-serum samples in column-switching LC with fluorescence detection.
PubMed: 30773513
DOI: 10.2116/analsci.19P011 -
Journal of Pharmaceutical and... Sep 2018Equine hair is becoming an increasingly popular biological matrix for doping control of horse sports; one of the reasons for this is the significantly longer detection...
Equine hair is becoming an increasingly popular biological matrix for doping control of horse sports; one of the reasons for this is the significantly longer detection window hair can offer. Hair analysis opens up the opportunity for longitudinal monitoring of drug exposure which would otherwise not be possible with the more traditional and common biological matrices, such as urine and blood. As such, there is a need for more multi-target screening methods covering a broad range of prohibited substances in equine hair at the required sensitivities for equine doping control. This paper describes a sensitive ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS) method for the detection of 121 drugs and/or their metabolites in equine hair covering ten classes of prohibited substances with estimated limits of detection between 0.1 and 10 pg/mg. To our knowledge, this is the first report of a screening method in equine hair which can cover such a broad range and well over one hundred prohibited substances in a single analytical run. This method has been validated for its specificity, precision and extraction recovery. Applicability of this method has been demonstrated by: (i) the successful identification of clenbuterol, 2-(1-hydroxyethyl) promazine sulfoxide, acepromazine and tetrahydrozoline in genuine equine mane samples; as well as (ii) the detection of drugs from artificially incurred mane hair samples which have been prepared by soaking blank hair samples in solutions of drug targets.
Topics: Anabolic Agents; Animals; Chromatography, High Pressure Liquid; Doping in Sports; Hair; Horses; Sensitivity and Specificity; Solid Phase Extraction; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 29885604
DOI: 10.1016/j.jpba.2018.05.043 -
Talanta Aug 2018SALDI-MS analysis of pharmaceutical drug molecules (amitriptyline, imipramine and promazine) using carbon-based substrates, namely, activated charcoal (AC), carbon...
SALDI-MS analysis of pharmaceutical drug molecules (amitriptyline, imipramine and promazine) using carbon-based substrates, namely, activated charcoal (AC), carbon nanotubes (CNTs), carbon black (CB), graphene (rGO), graphene oxide (GO) and graphite, was explored and compared with the conventional organic matrix of MALDI. CB exhibited superior performance with respect to the other substrates in terms of detection sensitivity. Despite the effectiveness of CB to detect all drug molecules, it demonstrated a number of background signals, which may be an issue for the analysis of other molecules in the future. Therefore, for the first time, a CeO-CB nanocomposite was synthesized and applied as a novel SALDI substrate to minimize the background signals and stabilize CB when exposed to high laser power. The nanocomposite was characterized using XRD, TEM, FTIR, UV-Vis and N sorpometry. The spectrum obtained using the novel nanocomposite in the absence of the drug molecules showed minimal background signals compared to CB. Additionally, the CeO-CB nanocomposite enhanced the detection sensitivity of the drug molecules with a limit of detection (LOD) of 100 ng/mL. This active substrate nanocomposite was further applied for the analysis of drug-spiked beverages without sample pretreatment or extraction, mimicking cases encountered by forensic toxicologists. All of the drugs and/or their adducts were detected in the drug-spiked beverage samples.
Topics: Beverages; Cerium; Nanocomposites; Particle Size; Pharmaceutical Preparations; Soot; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface Properties
PubMed: 29759225
DOI: 10.1016/j.talanta.2018.03.102 -
Spectrochimica Acta. Part A, Molecular... Jun 2018Aggregation behavior of bio-surfactants (BS) sodium cholate (NaC) and sodium deoxycholate (NaDC) within aqueous solution of ionic liquid (IL) 1-ethyl-3-methylimidazolium...
Self-aggregation of bio-surfactants within ionic liquid 1-ethyl-3-methylimidazolium bromide: A comparative study and potential application in antidepressants drug aggregation.
Aggregation behavior of bio-surfactants (BS) sodium cholate (NaC) and sodium deoxycholate (NaDC) within aqueous solution of ionic liquid (IL) 1-ethyl-3-methylimidazolium bromide [Emim][Br] has been investigated using surface tension, conductivity, steady state fluorescence, FT-IR and dynamic light scattering (DLS) techniques. Various interfacial and thermodynamic parameters are determined in the presence of different wt% of IL [Emim][Br]. Information regarding the local microenvironment and size of the aggregates is obtained from fluorescence and DLS, respectively. FT-IR spectral response is used to reveal the interactions taking place within aqueous NaC/NaDC micellar solutions. It is noteworthy to mention that increasing wt% of [Emim][Br] results in an increase in the spontaneity of micelle formation and the hydrophilic IL shows more affinity for NaC as compared to NaDC. Further, the micellar solutions of BS-[Emim][Br] are utilized for studying the aggregation of antidepressants drug promazine hydrochloride (pH). UV-vis spectroscopic investigation reveals interesting outcomes and the results show changes in spectral absorbance of PH drug on the addition of micellar solution (BS-[Emim][Br]). Highest binding affinity and most promising activity are shown for NaC as compared to NaDC.
Topics: Antidepressive Agents; Deoxycholic Acid; Humans; Hydrophobic and Hydrophilic Interactions; Imidazoles; Ionic Liquids; Micelles; Sodium Cholate; Surface Tension; Surface-Active Agents; Thermodynamics
PubMed: 29635182
DOI: 10.1016/j.saa.2018.03.079 -
RSC Advances Feb 2018Ionic liquids (ILs) and deep eutectic solvents (DESs) are receiving increased attention from both academic and industrial research due to their immense application...
Ionic liquids (ILs) and deep eutectic solvents (DESs) are receiving increased attention from both academic and industrial research due to their immense application potential. These designer solvents are environmentally friendly in nature with tunable physicochemical properties. In the present investigation, we have studied the aggregation behavior of a short-chain IL 1-butyl-3-methylimidazolium octylsulphate [Bmim][OS] within aqueous DESs using fluorescence, UV-vis, dynamic light scattering (DLS) and FT-IR spectroscopic techniques. We have prepared two DESs, ChCl-urea and ChCl-Gly, which are obtained by heating a mixture of an ammonium salt choline chloride with hydrogen bond donor urea or glycerol, respectively, in 1 : 2 molar ratios. The local microenvironment and size of the aggregates are obtained from steady state fluorescence (using pyrene and pyrene-1-carboxaldehyde as polarity probes) and DLS measurements, respectively. DLS results shows that IL [Bmim][OS] forms relatively larger micelles within the aqueous solution of DES ChCl-urea (avg. hydrodynamic radii = 209 nm) than compared to ChCl-Gly (avg. hydrodynamic radii = 135 nm). A significant decrease in the critical micelle concentration and increase in the aggregation number ( ) are observed within DES solutions as compared to that in water, thus indicating that the micellization process of the IL [Bmim][OS] is much favored in the DES solutions. Molecular interactions of [Bmim][OS] in DESs are revealed from FT-IR spectroscopic investigation. Furthermore, these systems were applied to study the IL-drug binding of the antidepressant drug promazine hydrochloride (PH).
PubMed: 35542011
DOI: 10.1039/c7ra13557b -
Journal of Veterinary Pharmacology and... Aug 2018Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of...
Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL) administration. Fifteen exercised adult Thoroughbred horses received a single intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine samples were collected at time 0 and at various times for up to 72 hr and analyzed for acepromazine and its two major metabolites (2-(1-hydroxyethyl) promazine and 2-(1-hydroxyethyl) promazine sulfoxide) using liquid chromatography-tandem mass spectrometry. Acepromazine was also incubated in vitro with whole equine blood and serum concentrations of the parent drug and metabolites determined. Acepromazine was quantitated for 24 hr following intravenous administration and 72 hr following oral and SL administration. Results of in vitro incubations with whole blood suggest additional metabolism by RBCs. The mean ± SEM elimination half-life was 5.16 ± 0.450, 8.58 ± 2.23, and 6.70 ± 2.62 hr following intravenous, oral, and SL administration, respectively. No adverse effects were noted and horses appeared sedate as noted by a decrease in chin-to-ground distance within 5 (i.v.) or 15 (p.o. and SL) minutes postadministration. The duration of sedation lasted 2 hr. Changes in heart rate were minimal.
Topics: Acepromazine; Administration, Oral; Administration, Sublingual; Animals; Chromatography, Liquid; Female; Horses; Hypnotics and Sedatives; Infusions, Intravenous; Male; Physical Conditioning, Animal; Tandem Mass Spectrometry
PubMed: 29457257
DOI: 10.1111/jvp.12494 -
PloS One 2018Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described...
Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity.
Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs) on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC) assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio), the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration.
Topics: Anti-Bacterial Agents; Antipsychotic Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; In Vitro Techniques; Lipids; Microbial Sensitivity Tests; Nanocapsules
PubMed: 29298353
DOI: 10.1371/journal.pone.0189950 -
Contact Dermatitis Sep 2017
Topics: Aged; Antipsychotic Agents; Dermatitis, Photoallergic; Humans; Male; Promazine
PubMed: 28766806
DOI: 10.1111/cod.12797 -
Cureus Feb 2017In recent years, antipsychotic medications have increasingly been used in pediatric and geriatric populations, despite the fact that many of these drugs were approved...
In recent years, antipsychotic medications have increasingly been used in pediatric and geriatric populations, despite the fact that many of these drugs were approved based on clinical trials in adult patients only. Preliminary studies have shown that the "off-label" use of these drugs in pediatric and geriatric populations may result in adverse events not found in adults. In this study, we utilized the large-scale U.S. Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) database to look at differences in adverse events from antipsychotics among adult, pediatric, and geriatric populations. We performed a systematic analysis of the FDA AERS database using MySQL by standardizing the database using structured terminologies and ontologies. We compared adverse event profiles of atypical versus typical antipsychotic medications among adult (18-65), pediatric (age < 18), and geriatric (> 65) populations. We found statistically significant differences between the number of adverse events in the pediatric versus adult populations with aripiprazole, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and thiothixene, and between the geriatric versus adult populations with aripiprazole, chlorpromazine, clozapine, fluphenazine, haloperidol, paliperidone, promazine, risperidone, thiothixene, and ziprasidone (p < 0.05, with adjustment for multiple comparisons). Furthermore, the particular types of adverse events reported also varied significantly between each population for aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (Chi-square, p < 10). Diabetes was the most commonly reported side effect in the adult population, compared to behavioral problems in the pediatric population and neurologic symptoms in the geriatric population. We also found discrepancies between the frequencies of reports in AERS and in the literature. Our analysis of the FDA AERS database shows that there are significant differences in both the numbers and types of adverse events among these age groups and between atypical and typical antipsychotics. It is important for clinicians to be mindful of these differences when prescribing antipsychotics, especially when prescribing medications off-label.
PubMed: 28465867
DOI: 10.7759/cureus.1059 -
The Science of the Total Environment Apr 2017Pharmaceuticals do not occur isolated in the environment but in multi-component mixtures and may exhibit antagonist, synergistic or additive behavior. Knowledge on this...
Pharmaceuticals do not occur isolated in the environment but in multi-component mixtures and may exhibit antagonist, synergistic or additive behavior. Knowledge on this is still scarce. The situation is even more complicated if effluents or potable water is treated by oxidative processes or such transformations occur in the environment. Thus, determining the fate and effects of parent compounds, metabolites and transformation products (TPs) formed by transformation and degradation processes in the environment is needed. This study investigated the fate and preliminary ecotoxicity of the phenothiazine pharmaceuticals, Promazine (PRO), Promethazine (PRM), Chlorpromazine (CPR), and Thioridazine (THI) as single and as components of the resulting mixtures obtained from their treatment by Fenton process. The Fenton process was carried out at pH7 and by using 0.5-2mgL of [Fe] and 1-12.5mgL of [HO] at the fixed ratio [Fe]:[HO] of 1:10 (w:w). No complete mineralization was achieved. Constitutional isomers and some metabolite-like TPs formed were suggested based on their UHPLC-HRMS data. A degradation pathway was proposed considering interconnected mechanisms such as sulfoxidation, hydroxylation, N-dealkylation, and dechlorination steps. Aerobic biodegradation tests (OECD 301 D and OECD 301 F) were applied to the parent compounds separately, to the mixture of parent compounds, and for the cocktail of TPs present after the treatment by Fenton process. The samples were not readily biodegradable. However, LC-MS analysis revealed that abiotic transformations, such hydrolysis, and autocatalytic transformations occurred. The initial ecotoxicity tested towards Vibrio fischeri as individual compounds featured a reduction in toxicity of PRM and CPR by the treatment process, whereas PRO showed an increase in acute luminescence inhibition and THI a stable luminescence inhibition. Concerning effects of the mixture components, reduction in toxicity by the Fenton process was predicted by concentration addition and independent action models.
Topics: Hydrogen Peroxide; Iron; Phenothiazines; Waste Disposal, Fluid; Water Pollutants, Chemical
PubMed: 28126283
DOI: 10.1016/j.scitotenv.2016.12.184