Tag: M.W=350-400

Zhang, Tao published the artcileAssessing Food Effects on Oral Drug Absorption Based on the Degree of Renal Excretion, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is AAPS Journal (2021), 23(3), 47, database is CAplus and MEDLINE.

Food intake influences the pharmacokinetics of orally administered drugs by altering drug absorption, metabolism, and excretion. A drug which is mainly excreted into urine as parent drug is usually highly water-soluble and metabolically stable. Food intake is not expected to significantly affect its extent of oral absorption, metabolism, and excretion. Therefore, we hypothesize that an orally administered drug with significant renal excretion should not have a dramatic food effect (FE). To test our hypothesis, we summarized the FE for orally administered immediate-release (IR) and modified-release (MR) formulations approved by the US FDA from 1998 to 2019, focusing on drugs undergoing significant renal excretion. Totally, 98 active pharmaceutical ingredients (APIs) in IR formulations and 34 APIs in MR formulations were selected. The results demonstrate that the area-under-the-curve (AUC) for IR drug products with f_{ur_cunchanged_cpo} > 10% is unlikely to be affected by food, although the peak plasma concentration (C_max) may increase or decrease by up to 50%. Compared with IR drug products with f_{ur_cunchanged_cpo} > 10%, MR drug products with f_{ur_cunchanged_cpo} > 10% tend to have more significant FE. Although our proposed approach cannot substitute a clin. FE study, it could be a useful addition to early drug development to get an initial sense of the potential for FE for a drug candidate.

AAPS Journal published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C9H17NO, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Anonymous published the artcileA condensation product between 5,8,14-triazatetracyclo[10.3.1.02,11.04,9]hexadeca-2(11),3,5,7,9-pentaene and lactose, Computed Properties of 375815-87-5, the publication is IP.com Journal (2009), 9(3B2), 2, database is CAplus.

A reaction of L-tartaric acid with 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine (Chantix, varenicline) provided Chantix L-tartrate. A reaction of that compound with lactose [i.e., 4-O-β-D-galactopyranosyl-D-glucose] gave a mixture of 4-O-[6-(7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepin-8-yl)-β-D-galactopyranosyl]-β-D-glucopyranose and 4-O-(β-D-galactopyranosyl)-6-deoxy-6-(7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepin-8-yl)-β-D-glucopyranose.

IP.com Journal published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Computed Properties of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Ericson, Jon F. published the artcileEvaluation of the OECD 314B Activated Sludge Die-Away Test for Assessing the Biodegradation of Pharmaceuticals, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Environmental Science & Technology (2010), 44(1), 375-381, database is CAplus and MEDLINE.

The European Medicines Agency guideline for the environmental risk assessment of medicinal products provides a step-by-step phased approach to evaluate the potential risks of new medicines to the environment. Phase I (prescreen) estimates the initial exposure of the new medicine in the environment. Phase II A (screen) estimates the fate and effects in the environment. The fate screen determines the inherent properties of the new medicinal active ingredient to sorb to sludge, soil, and sediment matrixes and its potential to degrade in a sewage treatment plant and in the subsequent water-sediment compartment. Current ERA Guidance (2006) recommends the OECD 301B Ready Biodegradation Test for Phase II Tier A testing without a clear recommendation for Phase II Tier B testing when further refinement may be needed. With the recent approval of the OECD 314B method for activated sludge, there is now an alternative test method that may be better suited for Phase II Tier A testing and to the data needs of the ERA. As a batch test, it fits the needs of a Tier A screen. It is not designed to simulate the operational steps of a sewage treatment plant, such as the OECD 303 tests, and yet provides the following without considerable costs or resources of OECD 303: (1) useful kinetic information in a test that reflects the conditions of the sewage-treatment environment, i.e., realistic biomass solids concentrations and low level test material concentrations to simulate 1st-order (nongrowth) kinetics, (2) mass balance anal. for CO₂ evolution and for residues found in mixed liquor, (3) use of an abiotic control to assess losses other than those attributed to biotic biodegradation, and (4) biotransformation profile of degradants. This paper presents the results of OECD 301B with that of OECD 314B for activated sludge biodegradation for 5 Pfizer drug substances. The use of this new method as an alternative to OECD 301B would strengthen the fate testing screen in Phase II Tier A of the EMEA ERA. It would provide a characterization of a substance’s potential for biotransformation and mineralization during sewage treatment and provide a means for revising predicted environmental concentration of surface water for amount removed during sewage treatment.

Environmental Science & Technology published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Lu, Yuting published the artcileImpurity profiling of varenicline tartrate by LC-QTOF mass spectrometric techniques during drug development, Product Details of C17H19N3O6, the publication is Journal of Pharmaceutical and Biomedical Analysis (2018), 306-313, database is CAplus and MEDLINE.

HPLC-QTOF-MS method was developed for the separation and characterization of related substances in varenicline tartrate drug material. The separation used InertSustain C18 column (4.6 × 150 mm, 5 μm) with liner gradient elution using 0.05% trifluoroacetic acid as mobile phase A and acetonitrile as mobile phase B. The degradation studies were conducted under the ICH prescribed stress conditions. Varenicline tartrate was unstable to alk., oxidative, thermal and photolytic stresses, but relatively stable under acid stress condition. Thirteen related substances were found in varenicline tartrate and its stressed samples. Their structures were identified mainly through pos. ESI high resolution QTOF mass spectrometric anal. of the parent and product ion accurate masses and the calculated elemental compositions Among the 13 substances, 7 were process-related and 6 were degradation products, and two of them were further verified by chem. synthesis and NMR spectroscopic determination Their formation mechanisms are discussed, and the key steps in the manufacturing processes are determined to provide varenicline tartrate with high purity.

Journal of Pharmaceutical and Biomedical Analysis published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Product Details of C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Piestansky, Juraj published the artcileComparison of hydrodynamically closed two-dimensional capillary electrophoresis coupled with ultraviolet detection and hydrodynamically open capillary electrophoresis hyphenated with mass spectrometry in the bioanalysis of varenicline, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Journal of Separation Science (2017), 40(10), 2292-2303, database is CAplus and MEDLINE.

Two capillary electrophoresis methods for monitoring renally excreted varenicline, a highly effective drug prescribed for smoking cessation, in human urine were developed and compared. A method combining capillary electrophoresis with mass spectrometry was proposed for the fast anal. of varenicline (anal. time up to 7 min). Here, mass spectrometry was a prerequisite for achieving high sensitivity and selectivity of the anal. suitable for the quantification of a 15 ng/mL level of varenicline in un-pretreated urine matrixes. An alternative approach, two-dimensional (column-coupled) capillary electrophoresis with enhanced sample load capacity and UV detection, was proposed as a low-cost alternative to capillary electrophoresis with mass spectrometry. The isotachophoresis online sample treatment included simple elimination of the major matrix constituents and stacking of the sample in a large volume so that threefold lower quantitation limits could be easily achieved in comparison to the capillary electrophoresis with mass spectrometry. On the other hand, longer anal. time (ca. 4.5-fold) and more complex electrolyte system in the coupled zone electrophoresis step (including two additives enhancing separation selectivity, i.e. isopropanol and cyclodextrin) were prerequisites for the complete separation of varenicline from the sample matrix. Anyway, both the developed methods were validated according to the Food and Drug Administration guidelines showing favorable performance parameters, suitable for their routine biomedical use.

Journal of Separation Science published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Kajiwara, Moto published the artcileRenal tubular secretion of varenicline by multidrug and toxin extrusion (MATE) transporters, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Drug Metabolism and Pharmacokinetics (2012), 27(6), 563-569, database is CAplus and MEDLINE.

Multidrug and toxin extrusion (MATE) 1 and MATE2-K, H⁺/organic cation antiporters, are located at the brush-border membrane of renal proximal tubules. The present study aimed to clarify the role of MATE transporters in tubular secretion of varenicline. Varenicline at a dose of 5 mg/kg was administered to wild-type and Mate1-knockout mice via the jugular vein, and its uptake was measured by high-performance liquid chromatog. The renal secretory clearance of and systemic exposure to varenicline were significantly decreased (54.6%, p < 0.05) and increased (116%, p < 0.05) resp., by the genetic disruption of Mate1 in mice. Uptake of varenicline and [¹⁴C]tetraethylammonium (TEA) was examined in HEK293 cells transiently expressing the human (h) MATE1, hMATE2-K, mouse (m) MATE1, and hOCT2 basolateral organic cation transporter. [¹⁴C]TEA uptake in HEK293 cells expressing MATE transporters and hOCT2 was decreased in the presence of varenicline. The calculated IC₅₀ values for hMATE1, hMATE2-K, mMATE1, and hOCT2 were 62.2 ± 6.5, 122.3 ± 67.6, 255.0 ± 37.9, and 1,003.9 ± 135.8 (μM; mean ± S.E. for three sep. experiments), resp. Varenicline uptake was significantly increased in HEK293 cells expressing mMATE1, hMATE1, or hMATE2-K cDNA as well as hOCT2 compared to empty vector-transfected cells. In conclusion, renal MATE transporters were found to be responsible for renal tubular secretion of varenicline.

Drug Metabolism and Pharmacokinetics published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Dowling, Thomas C. published the artcileEvaluation of renal drug dosing: prescribing information and clinical pharmacist approaches, COA of Formula: C17H19N3O6, the publication is Pharmacotherapy (2010), 30(8), 776-786, database is CAplus and MEDLINE.

Study Objective: To characterize renal function parameters reported in United States Food and Drug Administration-approved prescribing information (package inserts), to compare dosage recommendations for patients with impaired renal function between prescribing information and tertiary drug dosing references, and to evaluate renal function quantification methods most commonly used by clin. pharmacists to develop dosage regimens. Design: Retrospective anal. and Web-based survey. Data Sources: Prescribing information for all new mol. entities (NMEs) approved from 1998-2007 in which dosing recommendations were proposed for patients with impaired renal function, drug monographs from four tertiary drug dosing references (Micromedex, Lexi-Comp, Epocrates Rx, and American Hospital Formulary Service [AHFS] Drug Information) for all identified NMEs, and a Web-based survey of 204 nephrol. and critical care pharmacy practitioners. Measurements and Main Results: A total of 44 NMEs included renal dosing recommendations in their prescribing information. For all 44 NMEs, prescribing information was reviewed to determine methods to quantify renal function, units of measure reported, and use of chronic kidney disease terminol. The most common index of renal function was creatinine clearance; the Cockcroft-Gault equation was specified in the prescribing information of 11 NMEs. Standardization for body weight was inconsistent, with prescribing information for four NMEs reporting renal function in ml/min/1.73 m². The prescribing information or tertiary sources did not mention use of estimated glomerular filtration rate (eGFR) or the Modification of Diet in Renal Disease Study (MDRD) equation. Epocrates Rx provided the most abbreviated renal dosing information, whereas AHFS Drug Information was the most comprehensive, and Lexi-Comp includes a renal function calculator. Nearly all (86%) clin. pharmacists indicated that automated eGFR is reported at their institutions, although they do not use these predictions for dosing in patients with impaired renal function, and their approaches to renal function estimation varied widely. Conclusion: Reporting of renal function methods and dosing recommendations for patients with impaired renal function requires standardization in order to ensure optimal dosing. Pharmacy clinicians do not substitute eGFR in place of creatinine clearance for renal dosing, which is consistent with current prescribing information. Studies are needed that will evaluate the validity of using eGFR to predict drug clearance and thereby generate dosage recommendations.

Pharmacotherapy published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, COA of Formula: C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Piyankarage, Sujeewa C. published the artcileAutomated Solid Phase Extraction and Polarity-Switching Tandem Mass Spectrometry Technique for High Throughput Analysis of Urine Biomarkers for 14 Tobacco-related Compounds, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is ACS Omega (2021), 6(46), 30901-30909, database is CAplus and MEDLINE.

Tobacco use is the leading preventable cause of premature disease and death in the United States. Approx., 34 million U.S. adults currently smoke cigarettes. We developed a method for automated sample preparation and liquid chromatog.-tandem mass spectrometry quantitation of 14 tobacco-related analytes: nicotine (NICF), cotinine (COTF), trans-3′-hydroxycotinine (HCTF), menthol glucuronide (MEG), anabasine (ANBF), anatabine (ANTF), isonicoteine (ISNT), myosmine (MYOS), beta-nicotyrine (BNTR), bupropion (BUPR), cytisine (CYTI), varenicline (VARE), arecaidine (ARD), and arecoline (ARL). The method includes automated solid-phase extraction using customized pos.-pressure functions. The preparation scheme has the capacity to process a batch of 96 samples within 4 h with greater than 88% recovery for all analytes. The 14 analytes, separated within 4.15 min using reversed-phase liquid chromatog., were determined using a triple-quadrupole mass spectrometer with atm.-pressure chem. ionization and multiple reaction monitoring in neg. and pos. ionization modes. Wide quantitation ranges, within 1.2-72,000 ng/mL, were established especially for COTF, HCTF, MEG, and NICF to quantify the broad range of biomarker concentrations found in the U.S. population. The method accuracy is above 90% while the overall imprecision is below 7%. Finally, we tested urine samples from 90 smokers and observed detection rates of over 98% for six analytes with urinary HCTF and MEG concentrations ranging from 200-14,100 and 60-57,100 ng/mL, resp. This high throughput anal. process can prepare and analyze a sample in 9 min and along with the 14-compound analyte panel can be useful for tobacco-exposure studies, in smoking-cessation programs, and for detecting changes in exposure related to tobacco products and their use.

ACS Omega published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Channabasavaraj, K. P. published the artcileDevelopment and validation of RP-HPLC method for estimation of varenicline tartrate in bulk drug and tablet dosage form, Computed Properties of 375815-87-5, the publication is International Journal of Pharmacy and Pharmaceutical Sciences (2011), 3(2), 59-61, database is CAplus.

A reverse phase high performance liquid chromatog. method was developed and validated for the estimation of varenicline tartrate in bulk and tablet using UV detector. Gradient chromatog. was performed on a C₁₈ column, with a mobile phase composed by methanol:potassium dihydrogen orthophosphate buffer pH 3 (50:50, volume/volume), at flow rate of 0.6 mL/min using UV detection at 237 nm. The retention time for Varenicline tartrate was found to be 2.966 min. Linearity of the method was found to be 10 to 50 μg/mL, with the regression coefficient of 0.9999. This method was validated according to ICH guidelines. The intra-day and inter day percentage relative standard deviation (RSD) was found 0.327 and 0.147 resp. The proposed method was successfully applied for the quant. determination of varenicline tartrate in tablet formulations.

International Journal of Pharmacy and Pharmaceutical Sciences published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Computed Properties of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Dave, Rutwij A. published the artcileNovel high/low solubility classification methods for new molecular entities, COA of Formula: C17H19N3O6, the publication is International Journal of Pharmaceutics (Amsterdam, Netherlands) (2016), 511(1), 111-126, database is CAplus and MEDLINE.

This research describes a rapid solubility classification approach that could be used in the discovery and development of new mol. entities. Compounds (N = 635) were divided into two groups based on information available in the literature: high solubility (BDDCS/BCS 1/3) and low solubility (BDDCS/BCS 2/4). We established decision rules for determining solubility classes using measured log solubility in molar units (MLogS_M) or measured solubility (MSol) in mg/mL units. ROC curve anal. was applied to determine statistically significant threshold values of MSol and MLogS_M. Results indicated that NMEs with MLogS_M > -3.05 or MSol > 0.30 mg/mL will have ≥85% probability of being highly soluble and new mol. entities with MLogS_M ≤ -3.05 or MSol ≤ 0.30 mg/mL will have ≥85% probability of being poorly soluble When comparing solubility classification using the threshold values of MLogS_M or MSol with BDDCS, we were able to correctly classify 85% of compounds We also evaluated solubility classification of an independent set of 108 orally administered drugs using MSol (0.3 mg/mL) and our method correctly classified 81% and 95% of compounds into high and low solubility classes, resp. The high/low solubility classification using MLogS_M or MSol is novel and independent of traditionally used dose number criteria.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, COA of Formula: C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider