Month: November 2022

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

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

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

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

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

Cao, Qi published the artcileMechanism research on CSE restraining macrophages into foam cells by calcium sensing receptor, Quality Control of 226878-01-9, the publication is Xiandai Yufang Yixue (2015), 42(19), 3555-3559, 3596, database is CAplus.

Objective To confirm calcium sensing receptor (CaR) can increase the expression of CSE and the secretion of H₂S, thereby inhibiting the transformation of macrophages into foam cells. Methods Sensitive sulfur electrodes method was used to detect the change of the H₂S content in macrophages. The relative content of pos. cells was tested by oil red O staining and the HPLC method was sued to do the determination of intracellular cholesterol content. ELISA assay detected the secretion situation of cytokine IL-10, MIF, and TNF-α. The expression of CaR, CSE, CD36 and ACAT-1 in each group cells were detected by Western blot. Results Compared with the blank control group, the relative contents of H₂S in the GdCl₃ group and the NaHS group significantly increased, while the NPS2390 group, the relative content of H₂S significantly decreased. The number of pos. cells in the GdCl₃ group and the NaHS group obviously decreased, while the number in NPS2390 group adversely increased. The levels of TNF-α and MIF in cell supernatant significantly ascended, and the IL-10 level fell in the GdCl₃ and NaHS groups. However, there was a rising trend on the levels of TNF-α and MIF in cell supernatant, and the IL-10 level dropped significantly in the NPS2390 group. The expression of CaR and CSE significantly enhanced in GdCl₃ group, while the expression of CD36 and ACAT-1 were significantly inhibited in GdCl₃ group. Meanwhile, the expressions of CaR and CSE were significantly inhibited in NPS2390 group, while the expression of CD36 and ACAT-1 were significantly enhanced in NPS2390 group. GdCl₃ group significantly increased the expression of CSE, while GdCl₃ + CSE siRNA group and CSE siRNA group significantly reduced the expression of CSE. GdCl₃ group significantly increased the relative content of H₂S, while GdCl₃ + CSE siRNA group and CSE siRNA group significantly reduced the relative content of H₂S. Conclusion CaR could enhance the expression of CSE in macrophages to increase the secretion of H₂S, thereby inhibiting the transformation of macrophages into foam cells.

Xiandai Yufang Yixue published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Quality Control of 226878-01-9.

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

Liu, Cong published the artcileThe extracellular calcium-sensing receptor promotes porcine egg activation via calcium/calmodulin-dependent protein kinase II, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Molecular Reproduction & Development (2020), 87(5), 598-606, database is CAplus and MEDLINE.

Extracellular calcium is required for intracellular Ca²⁺ oscillations needed for egg activation, but the regulatory mechanism is still poorly understood. The present study was designed to demonstrate the function of calcium-sensing receptor (CASR), which could recognize extracellular calcium as first messenger, during porcine egg activation. CASR expression was markedly upregulated following egg activation. Functionally, the addition of CASR agonist NPS R-568 significantly enhanced pronuclear formation rate, while supplementation of CASR antagonist NPS2390 compromised egg activation. There was no change in NPS R-568 group compared with control group when the egg activation was performed without extracellular calcium addition The addition of NPS2390 precluded the activation-dependent [Ca²⁺]_i rise. When egg activation was conducted in intracellular Ca²⁺ chelator BAPTA-AM and NPS R-568 containing medium, CASR function was abolished. Meanwhile, CASR activation increased the level of the [Ca²⁺]_i effector p-CAMKII, and the presence of KN-93, an inhibitor of CAMKII, significantly reduced the CASR-mediated increasement of pronuclear formation rate. Furthermore, the increase of CASR expression following activation was reversed by inhibiting CAMKII activity, supporting a pos. feedback loop between CAMKII and CASR. Altogether, these findings provide a new pathway of egg activation about CASR, as the extracellular Ca²⁺ effector, promotes egg activation via its downstream effector and upstream regulator CAMKII.

Molecular Reproduction & Development published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

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

Liu, Chong published the artcileCaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress associated apoptotic pathways during ischemia/reperfusion, Application In Synthesis of 226878-01-9, the publication is International Journal of Molecular Medicine (2019), 44(3), 1117-1126, database is CAplus and MEDLINE.

Endoplasmic reticulum (ER) stress can be activated by ischemia/reperfusion (I/R) injury in cardiomyocytes. Persistent ER stress, with an increase in intracellular Ca²⁺ ([Ca²⁺]i) concentration, leads to apoptosis. Protein kinase C (PKC) has a key role in myocardial damage by elevation of [Ca²⁺]i. The calcium-sensing receptor (CaSR), a G protein-coupled receptor, can increase the release of [Ca²⁺]i from the ER through the inositol triphosphate receptor (IP₃R). Intracellular calcium overload has been demonstrated to cause cardiac myocyte apoptosis during I/R. However, the associations between PKC, CaSR and ER stress are not clear. The present study examined the hypothesis that activation of PKCδ by CaSR participates in ER stress-associated apoptotic pathways within myocardial I/R. Rat hearts were subjected to 30 min of ischemia in vivo, followed by reperfusion for 120 min. GdCl₃ (a CaSR activator) was used to elevate the intracellular Ca²⁺ concentration, but the Ca²⁺ concentration in the ER was significantly decreased during I/R. Following exposure to GdCl₃, expression levels of CaSR, glucose-regulated protein 78 (GRP78), Caspase-12, phosphorylated JNK and Caspase-3 were increased, and the ratios of apoptotic myocardial cells were significantly increased. By contrast, following exposure to rottlerin, a PKCδ inhibitor, the expression levels of these proteins and the ratio of apoptotic myocardial cells were significantly reduced. The present study also demonstrated that PKCd translocated into the ER to induce an ER stress response and participate in the ER stress-related apoptosis pathway. These results confirmed that CaSR activated PKCδ to induce cardiomyocyte apoptosis through ER stress-associated apoptotic pathways during I/R in vivo.

International Journal of Molecular Medicine published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Application In Synthesis of 226878-01-9.

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

Hernandez Zenteno, Rafael J. published the artcileVarenicline for long term smoking cessation in patients with COPD, COA of Formula: C17H19N3O6, the publication is Pulmonary Pharmacology & Therapeutics (2018), 116-120, database is CAplus and MEDLINE.

Quitting smoking is key for patients with Chronic Obstructive Pulmonary Disease (COPD). Standard recommendations for quitting smoking are implemented for COPD as well. Varenicline Tartrate (VT) is the most effective drug to help quit smoking, but few studies have analyzed its effectiveness. Aim of the study: To determine the Abstinence Rate (AR) at 12 mo, in COPD and non-COPD smokers. Observational study in 31 COPD (post bronchodilator-BD FEV₁/FVC <0.70) and in 63 non-COPD smokers, were invited to receive treatment with Varenicline Tartrate (VT). Fourteen subjects with COPD and 46 non-COPD subjects received addnl. Cognitive-Behavioral Therapy (CBT). Abstinence rate (AR) was validated by exhaled carbon monoxide CO (COe), in addition to a phone or face-to-face interview. Motivation score was measured with a visual analog scale (MS). Differences between COPD and non-COPD, mean FEV₁/FVC ratio 0.52 ± 0.10 vs. 0.90 ± 0.15, age 60 ± 10 vs. 47 ± 10 years, smoking pack-years 37 ± 3.5 vs. 22 ± 12, and COe 16 ± 11 vs. 12 ± 9 ppm were statistically significant (p < 0.05); for MS the score was 93 ± 11 vs. 93 ± 11 and for attempts to quit (AQ) 2 ± 2 vs. 2 ± 3 were not. AR was not significantly different at 12 mo (61.2 vs. 42.8% p = 0.072). Motivation was the only significant one-year AR predictor. COPD smokers had a similar response (higher tendency) to VT regardless of the presence of airflow obstruction and stronger nicotine addiction.

Pulmonary Pharmacology & Therapeutics 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

Satheesh, B. published the artcileUPLC separation and quantification of related substances of varenicline tartrate tablet, SDS of cas: 375815-87-5, the publication is Acta Chromatographica (2010), 22(2), 207-218, database is CAplus.

A new ultra-performance liquid chromatog. (UPLC) method was developed and validated for quantification of substances related to varenicline tartrate, process-related and degradation products, in pharmaceutical formulations. Chromatog. separation of 6 impurities was performed on a reversed phase column. The method was validated for linearity, limits of detection and quantification, accuracy, precision, and selectivity. The calibration plots obtained for the 6 impurities were linear over the range 0.005-0.30%. The relative standard deviations (s_r) of intra and inter-day experiments were < 1.0%. The detection limits ranged between 0.002 and 0.004%, depending on the impurity. The proposed UPLC method was successfully applied to quantification of varenicline impurities in its pharmaceutical formulation.

Acta Chromatographica 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, SDS of cas: 375815-87-5.

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