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Journal of Chromatographic Science Jan 2021Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently...
Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently integrated into the supportive treatment of COVID-19), propyphenazone (PZ) and caffeine (CF) in the presence of two PC impurities, namely 4-aminophenol and 4-nitrophenol. A "dual-mode" gradient high-performance liquid chromatography method was developed, where the separation was achieved via "dual-mode" gradient by changing both the ternary mobile phase composition (acetonitrile: methanol: water) and the flow rate. This enables a good resolution within a relatively shorter analysis time. The analysis was realized using Zorbax Eclipse XDB column C18, 5 μm (250 × 4.6 mm) and the UV detector was set at 220 nm. The other method is a thin-layer chromatography densitometry method, where the separation was achieved using a mobile phase composed of chloroform: toluene: ethyl acetate: methanol: acetic acid (6: 6: 1: 2: 0.1, by volume). Densitometric detection was performed at 220 nm on silica gel 60 F254 plates. The developed methods were fully validated as per the ICH guidelines and proved to be accurate, robust, specific and suitable for application as purity indicating methods for routine analysis of PC in pure form or in pharmaceuticals with PZ and CF in quality control laboratories.
Topics: Acetaminophen; Aminophenols; Antipyrine; Caffeine; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Codeine; Densitometry; Drug Combinations; Drug Contamination; Limit of Detection; Meprobamate; Nitrophenols; Reproducibility of Results; Sensitivity and Specificity; Solvents; Tablets
PubMed: 33221830
DOI: 10.1093/chromsci/bmaa088 -
Pharmaceutics Sep 2020Despite recent advances in bioinformatics, systems biology, and machine learning, the accurate prediction of drug properties remains an open problem. Indeed, because the...
Despite recent advances in bioinformatics, systems biology, and machine learning, the accurate prediction of drug properties remains an open problem. Indeed, because the biological environment is a complex system, the traditional approach-based on knowledge about the chemical structures-can not fully explain the nature of interactions between drugs and biological targets. Consequently, in this paper, we propose an unsupervised machine learning approach that uses the information we know about drug-target interactions to infer drug properties. To this end, we define drug similarity based on drug-target interactions and build a weighted Drug-Drug Similarity Network according to the drug-drug similarity relationships. Using an energy-model network layout, we generate drug communities associated with specific, dominant drug properties. DrugBank confirms the properties of 59.52% of the drugs in these communities, and 26.98% are existing drug repositioning hints we reconstruct with our DDSN approach. The remaining 13.49% of the drugs seem not to match the dominant pharmacologic property; thus, we consider them potential drug repurposing hints. The resources required to test all these repurposing hints are considerable. Therefore we introduce a mechanism of prioritization based on the betweenness/degree node centrality. Using betweenness/degree as an indicator of drug repurposing potential, we select Azelaic acid and Meprobamate as a possible antineoplastic and antifungal, respectively. Finally, we use a test procedure based on molecular docking to analyze Azelaic acid and Meprobamate's repurposing.
PubMed: 32947845
DOI: 10.3390/pharmaceutics12090879 -
Neuropharmacology Sep 2020Carisoprodol (Soma®) is a centrally-acting skeletal-muscle relaxant frequently prescribed for treatment of acute musculoskeletal conditions. Carisoprodol's mechanism of...
Carisoprodol (Soma®) is a centrally-acting skeletal-muscle relaxant frequently prescribed for treatment of acute musculoskeletal conditions. Carisoprodol's mechanism of action is unclear and is often ascribed to that of its active metabolite, meprobamate. The purpose of this study was to ascertain whether carisoprodol directly produces behavioral effects, or whether metabolism to meprobamate via cytochrome P450 (CYP450) enzymatic reaction is necessary. Rats were trained to discriminate carisoprodol (100 mg/kg) to assess time course and whether a CYP450 inhibitor (cimetidine) administered for 4 days would alter the discriminative effects of carisoprodol. Additionally, pharmacokinetics of carisoprodol and meprobamate with and without co-administration of cimetidine were assessed via in vivo microdialysis combined with liquid-chromatography-tandem mass spectrometry from blood and nucleus accumbens (NAc). The time course of the discriminative-stimulus effects of carisoprodol closely matched the time course of the levels of carisoprodol in blood and NAc, but did not match the time course of meprobamate. Administration of cimetidine increased levels of carisoprodol and decreased levels of meprobamate consistent with its interfering with metabolism of carisoprodol to meprobamate. However, cimetidine failed to alter the discriminative-stimulus effects of carisoprodol. Carisoprodol penetrated into brain tissue and directly produced behavioral effects without being metabolized to meprobamate. These findings indicate that understanding the mechanism of action of carisoprodol independently of meprobamate will be necessary to determine the validity of its clinical uses.
Topics: Animals; Carisoprodol; Discrimination Learning; Dose-Response Relationship, Drug; Male; Meprobamate; Muscle Relaxants, Central; Nucleus Accumbens; Rats; Rats, Sprague-Dawley
PubMed: 32479814
DOI: 10.1016/j.neuropharm.2020.108152 -
Chemosphere Jul 2020Emerging contaminants, especially, pharmaceutical and personal care products (PPCPs) are not removed well during conventional wastewater treatment and hence pose water...
Emerging contaminants, especially, pharmaceutical and personal care products (PPCPs) are not removed well during conventional wastewater treatment and hence pose water quality risk to the environment and potentially to public health. Long-term use of reclaimed wastewater for irrigation can lead to accumulation of trace contaminants in the soil, ground water and their subsequent uptake by plants and potentially can enter human food chain. This paper uses biochar as an adsorbent to remove emerging contaminants from treated wastewater by performing fixed bed experiments. Ten emerging contaminants namely, carbamazepine (CBZ), caffeine, diethyltoluamide (DEET), diphenhydramine (DPH), meprobamate (MPB), primidone (PMD), sulfamethoxazole (SMX), fluoxetine (FXT), perfluorooctanoic acid (PFOA) and trimethoprim (TMP) were monitored during lab scale experiments. Results from the continuous flow runs showed that the breakthrough curve for compounds caffeine, CBZ, DEET and PFOA follow second order Thomas model with adsorption capacities of 396 μg g, 392 μg g, 1160 μg g and 32 μg g biochar, respectively. Whereas compounds such as DPH, TMP and FXT were completely removed throughout the column runs by biochar. Results for rest of the compounds were interfered by leaching of these compounds from biochar. It was observed that commercially available GAC performed much better than biochar for all the compounds considered. Even at 1% of obtained capacity, biochar amendment to soils where reclaimed water is used for irrigation can reduce the uptake of these compounds by plants.
Topics: Adsorption; Agricultural Irrigation; Carbamazepine; Charcoal; Cosmetics; Groundwater; Humans; Soil; Soil Pollutants; Sulfamethoxazole; Waste Disposal, Fluid; Wastewater; Water; Water Pollutants, Chemical
PubMed: 32171942
DOI: 10.1016/j.chemosphere.2020.126403 -
International Journal of Molecular... Aug 2019From the past, we know how much "serendipity" has played a pivotal role in scientific discoveries. The definition of serendipity implies the finding of one thing while...
From the past, we know how much "serendipity" has played a pivotal role in scientific discoveries. The definition of serendipity implies the finding of one thing while looking for something else. The most known example of this is the discovery of penicillin. Fleming was studying "Staphylococcus influenzae" when one of his culture plates became contaminated and developed a mold that created a bacteria-free circle. Then he found within the mold, a substance that proved to be very active against the vast majority of bacteria infecting human beings. Serendipity had a key role in the discovery of a wide panel of psychotropic drugs as well, including aniline purple, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. Actually, many recent studies support a step back in current strategies that could lead to new discoveries in science. This change should seriously consider the idea that to further focus research project milestones that are already too focused could be a mistake. How can you observe something that others did not realize before you? Probably, one pivotal requirement is that you pay a high level of attention on what is occurring all around you. But this is not entirely enough, since, specifically talking about scientific discoveries, you should have your mind sufficiently unbiased from mainstream infrastructures, which normally make you extremely focused on a particular endpoint without paying attention to potential "unexpected discoveries". Research in medicine should probably come back to the age of innocence and avoid the age of mainstream reports that do not contribute to real advances in the curing of human diseases. Max Planck said "Science progresses not because scientists change their minds, but rather because scientists attached to erroneous views die, and are replaced", and Otto Warburg used the same words when he realized the lack of acceptance of his ideas. This editorial proposes a series of examples showing, in a practical way, how unfocused research may contribute to very important discoveries in science.
Topics: Chlorpromazine; Humans; Imipramine; Lysergic Acid Diethylamide; Meprobamate; Psychotropic Drugs
PubMed: 31443232
DOI: 10.3390/ijms20163973 -
Journal of Analytical Toxicology Oct 2019Toxicology laboratories commonly employ immunoassay methodologies to perform an initial drug screen on urine specimens to direct confirmatory testing. Due to limitations...
Toxicology laboratories commonly employ immunoassay methodologies to perform an initial drug screen on urine specimens to direct confirmatory testing. Due to limitations of immunoassay testing and the need to screen for a broader range of drugs with lower limits of detection at a lower cost, mass spectrometry screening techniques have gained favor in the toxicology field. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) urine screening panel was developed and validated for 52 drugs and metabolites. A simple dilute-and-shoot with enzymatic hydrolysis technique was utilized to prepare the urine specimens for analysis. Limit of detection, interference, ionization suppression/enhancement, carryover and stability of processed specimens were assessed during validation. To evaluate the toxicological results obtained from utilizing the LC-MS-MS in comparison with the laboratory's current enzyme-linked immunosorbent assay (ELISA) panel, 100 authentic urine specimens from suspected driving under the influence and drug-facilitated crime cases were analyzed using both methodologies and the results were compared. In addition, the cost of each methodology was evaluated and compared. The validated LC-MS-MS method had limits of detection that were equal to or lower than the concentrations validated for ELISA cutoffs, had fewer exogenous interferences, and the cost of screening per specimen was reduced by ~70% when compared to ELISA. Comparing the toxicology results of forensic urine specimens demonstrated that by only using ELISA, the laboratory was unable to detect benzoylecgonine in 26%, lorazepam in 33% and oxymorphone in 60% of the positive specimens. Additional analytes detected using the LC-MS-MS method were zolpidem and/or metabolite, gabapentin, tramadol and metabolite, methadone and metabolite, meprobamate and phentermine. The results of the validation, the toxicological result comparison and the cost comparison showed that the LC-MS-MS screening method is a simple, sensitive and cost-effective alternative to ELISA screening methods for urine specimens.
Topics: Chromatography, Liquid; Crime; Enzyme-Linked Immunosorbent Assay; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Immunoassay; Substance Abuse Detection; Tandem Mass Spectrometry; Urinalysis
PubMed: 31424082
DOI: 10.1093/jat/bkz066 -
Trace and bulk organics removal during ozone-biofiltration treatment for potable reuse applications.Water Environment Research : a Research... Mar 2020This study investigated impact of ozone/biological activated carbon (BAC) filtration design and operational parameters on contaminants of emerging concern (CEC) and bulk...
This study investigated impact of ozone/biological activated carbon (BAC) filtration design and operational parameters on contaminants of emerging concern (CEC) and bulk organics removal over 450 days of operation. Two parallel BAC filters with identical media and influent were maintained, each at a different empty bed contact time of 10 and 20 min. This study captured the CEC removal performance of a BAC filter over an extended operational period after treating 65,000 bed volumes. Ozone system was operated at ozone dose to TOC ratio range of 0.9-2. Biofilter with lower EBCT (10 min) and exhausted media resulted in poor removals of Tris(2-chloroethyl) phosphate (TCEP), perfluorooctanoic acid (PFOA), sucralose, meprobamate, N,N-diethyl-m-toluamide (DEET), and cotinine. Biofilter with higher EBCT (20 min) and remaining adsorptive effects resulted in significant (84% or more) removal of all CECs that were detected in the ozonated effluent. Increasing both ozone dose and BAC EBCT resulted in increased removal of UV absorbance (UVA ). The evaluation of impact of ozone:TOC ratio and BAC EBCT on CEC removal, bulk organics (TOC), and UVA performed in this study confirmed the importance of these two parameters on overall success of nonreverse osmosis (RO) potable reuse projects. PRACTITIONER POINTS: Ozone-BAC biofiltration is feasible strategy for indirect potable reuse water reclamation. Ozone-BAC empty bed contact time is a critical design parameter. Adsorption and biodegradation are both important mechanisms for trace organic contaminant removal in BAC.
Topics: Drinking Water; Filtration; Ozone; Water Pollutants, Chemical; Water Purification
PubMed: 31411786
DOI: 10.1002/wer.1202 -
Chemosphere Nov 2019The main objective of this study was to compare the efficacy of ozone (O) and O with granular activated carbon (GAC) (O/GAC) at pilot-scale for the enhanced removal of...
The main objective of this study was to compare the efficacy of ozone (O) and O with granular activated carbon (GAC) (O/GAC) at pilot-scale for the enhanced removal of micropollutants (MPs) from wastewater effluent. The results revealed enhanced removal of tris (2-carboxylethyl) phosphine (TCEP), sucralose, and meprobamate during the O/GAC treatment experiments compared to the sum of their removal during isolated ozonation and GAC adsorption experiments. The long-term O/GAC experiment showed the promotive effect of GAC substantially decreased after 20 h of O exposure. This decreased performance correlates with changes to GAC surface properties caused by O. After 6 h of operation, O initially led to an increase in Brunauer-Emmett-Teller (BET) surface area on the GAC improving the elimination level of investigated MPs (except N-nitrosomorpholine (NMOR)). However, after 20 h of exposure, O ultimately caused structural damages to the GAC surface, decreased the BET surface area in the final stages of the experiment, and a 4-fold increase in O:C ratio on the GAC surface was observed due to an increase in surface acidic functional groups caused by O treatment.
Topics: Adsorption; Carbon; Charcoal; Cities; Ozone; Wastewater; Water Pollutants, Chemical; Water Purification
PubMed: 31247495
DOI: 10.1016/j.chemosphere.2019.06.082