The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Zemfira A. Bredikhina - One of the best experts on this subject based on the ideXlab platform.
-
chirality dependent supramolecular synthons based on the 1 3 oxazolidin 2 one framework chiral drugs mephenoxalone Metaxalone and 114 other examples
CrystEngComm, 2020Co-Authors: A A Bredikhin, Zemfira A. Bredikhina, A T GubaidullinAbstract:In four of the five crystalline modifications of the muscle relaxants mephenoxalone 3 and Metaxalone 2, chain supramolecular motifs of three different types are realized. The centrosymmetric cyclic dimer, which is considered typical of amides, was found only once. To clarify the nature of the emerging supramolecular synthons, the set of 119 crystal structures of 1,3-oxazolidin-2-one 1 derivatives, to which drugs 2 and 3 belong, were selected from the Cambridge Structural Database. Analysis of the sample showed that oxazolidinone fragments predominantly form closed ring synthons in racemic crystals, whereas linear chains are typical for enantiopure ones. Thus, in the case of chiral objects, the transition from racemic to enantiopure crystal serves as a powerful tool for designing crystals with a given organization of supramolecular synthon. Two earlier unidentified kryptoracemates (false conglomerates), QEFJAP and QEFJUJ, were found among the analyzed set. Apparently, these are the first representatives of oxazolidinones exhibiting this rare property.
-
solid phase behavior polymorphism and crystal structure features of chiral drug Metaxalone
Crystal Growth & Design, 2018Co-Authors: Alexander A. Bredikhin, Dmitry V. Zakharychev, Aidar T. Gubaidullin, Zemfira A. BredikhinaAbstract:In addition to the previously known A-rac and B-rac polymorphs of the chiral drug Metaxalone 1, an enantiopure A-(S)-form was obtained and studied. According to X-ray analysis, the crystalline organization of this form is close to the A-rac-1 polymorph. Crystallization of Metaxalone melts is accompanied by the formation of a previously unknown metastable C-phase, which in the case of both racemic and enantiomeric samples are transformed into A-rac-1 or A-(S)-1. Analysis of the PXRD and IR spectra of crystalline samples revealed a similarity of the internal structure for the A-(S)-1, A-rac-1, C-(S)-1, and C-rac-1 crystalline forms and the essential difference of all of these phases from the B-rac-1 phase. According to the thermochemical data, the dependences of the change in the Gibbs free energy for all the phases studied are plotted in the interval from the melting point to 20 °C. Under standard conditions, the crystalline modifications of Metaxalone, relative to ΔG0, form such a series: B-rac-1 < A-(S)-...
-
Solid Phase Behavior, Polymorphism, and Crystal Structure Features of Chiral Drug Metaxalone
2018Co-Authors: Alexander A. Bredikhin, Dmitry V. Zakharychev, Aidar T. Gubaidullin, Zemfira A. BredikhinaAbstract:In addition to the previously known A-rac and B-rac polymorphs of the chiral drug Metaxalone 1, an enantiopure A-(S)-form was obtained and studied. According to X-ray analysis, the crystalline organization of this form is close to the A-rac-1 polymorph. Crystallization of Metaxalone melts is accompanied by the formation of a previously unknown metastable C-phase, which in the case of both racemic and enantiomeric samples are transformed into A-rac-1 or A-(S)-1. Analysis of the PXRD and IR spectra of crystalline samples revealed a similarity of the internal structure for the A-(S)-1, A-rac-1, C-(S)-1, and C-rac-1 crystalline forms and the essential difference of all of these phases from the B-rac-1 phase. According to the thermochemical data, the dependences of the change in the Gibbs free energy for all the phases studied are plotted in the interval from the melting point to 20 °C. Under standard conditions, the crystalline modifications of Metaxalone, relative to ΔG0, form such a series: B-rac-1 < A-(S)-1 ≈ A-rac-1 < C-rac-1 < C-(S)-1. A model that describes all the experimentally revealed features of Metaxalone crystallization is proposed
Poonam Vats - One of the best experts on this subject based on the ideXlab platform.
-
Metaxalone estimation in biological matrix using high throughput lc ms ms bioanalytical method
Journal of Chromatography B, 2012Co-Authors: Dipanjan Goswami, Arabinda Saha, Sanjay Gurule, Tausif Monif, Arshad Khuroo, Poonam VatsAbstract:Abstract Metaxalone is a skeletal muscle relaxant, an approved drug for pain relief. Published bioanalytical methods lacked detailed stability evaluation in blood and plasma. An accurate, precise, high-throughput tandem mass spectroscopic method has been developed and validated. Following solid phase extraction (SPE), Metaxalone and the internal standard Metaxalone-d3 were extracted from an aliquot of 200 μL of human plasma. Chromatographic separation achieved on an Ascentis Express C18 column (50 mm × 4.6 mm i.d., 2.7 μm particle size) with mobile phase is a mixture of 10 mM ammonium acetate buffer (pH 4.5)–methanol–acetonitrile (20:50:30, v/v/v), at an isocratic flow rate of 0.7 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The mass transitions of Metaxalone and Metaxalone-d3 were m/z 222.3 → 161.2 and m/z 225.3 → 163.3, respectively. The linear calibration curves were obtained in the concentration range of 0.105–10.081 μg/mL (r2 ≥ 0.99) with a lower limit of quantification (LLOQ) of 0.105 μg/mL. The intra- and inter-day precisions and relative error were all within 6%. Despite achieving high mean recovery (>78%), no interference peaks or matrix effects were observed. Detailed stability exercises including drug stability in blood, hemolyzed, lipemic and normal plasma were conducted to extend the method applicability in vast majority of clinical studies using 800 mg Metaxalone extended release oral dosage form.
Dipanjan Goswami - One of the best experts on this subject based on the ideXlab platform.
-
Metaxalone estimation in biological matrix using high throughput lc ms ms bioanalytical method
Journal of Chromatography B, 2012Co-Authors: Dipanjan Goswami, Arabinda Saha, Sanjay Gurule, Tausif Monif, Arshad Khuroo, Poonam VatsAbstract:Abstract Metaxalone is a skeletal muscle relaxant, an approved drug for pain relief. Published bioanalytical methods lacked detailed stability evaluation in blood and plasma. An accurate, precise, high-throughput tandem mass spectroscopic method has been developed and validated. Following solid phase extraction (SPE), Metaxalone and the internal standard Metaxalone-d3 were extracted from an aliquot of 200 μL of human plasma. Chromatographic separation achieved on an Ascentis Express C18 column (50 mm × 4.6 mm i.d., 2.7 μm particle size) with mobile phase is a mixture of 10 mM ammonium acetate buffer (pH 4.5)–methanol–acetonitrile (20:50:30, v/v/v), at an isocratic flow rate of 0.7 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The mass transitions of Metaxalone and Metaxalone-d3 were m/z 222.3 → 161.2 and m/z 225.3 → 163.3, respectively. The linear calibration curves were obtained in the concentration range of 0.105–10.081 μg/mL (r2 ≥ 0.99) with a lower limit of quantification (LLOQ) of 0.105 μg/mL. The intra- and inter-day precisions and relative error were all within 6%. Despite achieving high mean recovery (>78%), no interference peaks or matrix effects were observed. Detailed stability exercises including drug stability in blood, hemolyzed, lipemic and normal plasma were conducted to extend the method applicability in vast majority of clinical studies using 800 mg Metaxalone extended release oral dosage form.
P.V. Datla - One of the best experts on this subject based on the ideXlab platform.
-
Quantification of Metaxalone in human plasma by liquid chromatography coupled to tandem mass spectrometry
Journal of Analytical Toxicology, 2006Co-Authors: R.V.S. Nirogi, V.N. Kandikere, K. Mudigonda, W. Shrivastava, Mukul Shukla, P.V. DatlaAbstract:A simple, rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry (MS) method was developed and validated for the quantification of Metaxalone, a skeletal muscle relaxant, in human plasma using galantamine as internal standard (IS). Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse phase C18 column and analyzed by MS in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 222/161 for Metaxalone and m/z 288/213 for the IS. The assay exhibited a linear dynamic range of 50-5000 μg/L for Metaxalone in human plasma. The lower limit of quantification was 50 μg/L with a relative standard deviation of less than 10%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability, or bioequivalence studies.
Mathias B. Forrester - One of the best experts on this subject based on the ideXlab platform.
-
Adult Metaxalone ingestions reported to Texas poison control centers,
2016Co-Authors: Mathias B. Forrester, Metaxalone King PharmaceuticalsAbstract:Few data exist on potentially adverse Metaxalone (Skelaxin®) ingestions in adults. All Metaxalone ingestions involving patients aged ≥20 years during 2000-2006 were retrieved from Texas poison control centers. Exclu-sion criteria were lack of follow-up or multiple substance ingestion. Cases were analyzed for selected demo-graphic and clinical factors. Of the 142 patients, 66.2 % were female. Dose ingested was reported for 61 patients. Of those cases with a reported dose, distribution by management site was 29.5 % on-site, 59.0% already at/en route to health care facility, and 11.5 % referred to health care facility. Final medical outcome was ‘no effect ’ for 50.8 % cases, ‘minor effect ’ for 31.1%, and ‘moderate effect ’ for 18.0%. The more common adverse clinical effects reported were drowsiness (27.9%), tachycardia (6.6%), agitation (6.6%), nausea (4.9%), dizziness (4.9%), slurred speech (4.9%), and tremor (4.9%). A moderate medical outcome occurred in 13.6 % of ingestions of ≤2400 mg and 20.5 % of ingestions of>2400 mg. Management involved a health care facility in 18.2 % of ingestions of ≤2400 mg and 100.0 % of ingestions of>2400 mg. This study found that adult ingestions of higher doses of Metaxalone, particularly>2400 mg, were associated with more serious medical outcomes and were managed at health care facilities. This study also proposes triage guidelines for when inges-tions can be safely managed at home
-
pediatric Metaxalone ingestions reported to texas poison control centers 2000 2007
Pediatric Emergency Care, 2010Co-Authors: Mathias B. ForresterAbstract:OBJECTIVES:: The purpose of this study was to describe the pattern of Metaxalone (a muscle relaxant) ingestions by young children reported to poison control centers. METHODS:: Cases were all Metaxalone ingestions by patients aged 0 to 5 years reported to Texas poison control centers during 2000 to 2007. Cases with multiple substance ingestions and lack of follow-up were excluded. Cases were analyzed for selected demographic and clinical factors. RESULTS:: Of 148 total cases, 56.8% were boys. The distributions by management site were 56.1% on-site, 22.3% already at/en route to a health care facility, and 21.6% referred to a health care facility. Final medical outcomes were no effect for 90.5% cases, minor effect for 8.1%, moderate effect for 0.7%, and major effect for 0.7%. Specific clinical effects reported were drowsiness (11), vomiting (3), agitation (2), rash (1%), tachycardia (1), and ataxia (1). CONCLUSIONS:: Pediatric Metaxalone ingestions reported to Texas poison control centers usually resulted in minor or no effect. Most ingestions did not require hospitalization. Language: en
-
adult Metaxalone ingestions reported to texas poison control centers 2000 2006
Human & Experimental Toxicology, 2010Co-Authors: Mathias B. ForresterAbstract:Few data exist on potentially adverse Metaxalone (Skelaxin®) ingestions in adults. All Metaxalone ingestions involving patients aged ≥20 years during 2000-2006 were retrieved from Texas poison control centers. Exclusion criteria were lack of follow-up or multiple substance ingestion. Cases were analyzed for selected demographic and clinical factors. Of the 142 patients, 66.2% were female. Dose ingested was reported for 61 patients. Of those cases with a reported dose, distribution by management site was 29.5% on-site, 59.0% already at/en route to health care facility, and 11.5% referred to health care facility. Final medical outcome was ‘no effect’ for 50.8% cases, ‘minor effect’ for 31.1%, and ‘moderate effect’ for 18.0%. The more common adverse clinical effects reported were drowsiness (27.9%), tachycardia (6.6%), agitation (6.6%), nausea (4.9%), dizziness (4.9%), slurred speech (4.9%), and tremor (4.9%). A moderate medical outcome occurred in 13.6% of ingestions of ≤2400 mg and 20.5% of ingestions of >...