scholarly journals A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance

2009 ◽  
Vol 2009 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Victoria Silva Elipe ◽  
Zhixin Jessica Tan ◽  
Michael Ronk ◽  
Tracy Bostick
Keyword(s):  
Hplc Analysis ◽  
Scale Up ◽  
2D Nmr ◽  
Starting Material ◽  
Drug Substance ◽  
Synthetic Route ◽  
Stress Studies ◽  
Experimental Drug ◽  
Initial Scale

In the initial scale-up batches of the experimental drug substance AMG 517, a pair of unexpected impurities was observed by HPLC. Analysis of data from initial LC-MS experiments indicated the presence of two dimer-like molecules. One impurity had an additional sulfur atom incorporated into its structure relative to the other impurity. Isolation of the impurities was performed, and further structural elucidation experiments were conducted with high-resolution LC-MS and 2D NMR. The dimeric structures were confirmed, with one of the impurities having an unexpected C-S-C linkage. Based on the synthetic route of AMG 517, it was unlikely that these impurities were generated during the last two steps of the process. Stress studies on the enriched impurities were carried out to further confirm the existence of the C-S-C linkage in the benzothiazole portion of AMG 517. Further investigation revealed that these two dimeric impurities originated from existing impurities in the AMG 517 starting material, N-acetyl benzothiazole. The characterization of these two dimeric impurities allowed for better quality control of new batches of the N-acetyl benzothiazole starting material. As a result, subsequent batches of AMG 517 contained no reportable levels of these two impurities

Preparation and Characterization of Novel Methyl Acrylate

2011 ◽  
Vol 343-344 ◽  
pp. 1236-1241
Author(s):  
Yong En Guo ◽  
Jing Cao ◽  
Cai Ju Zhou ◽  
Shao Peng Wen ◽  
Ya Mei Zhang ◽  
...  
Keyword(s):  
1H Nmr ◽  
Methyl Acrylate ◽  
Salvianolic Acid B ◽  
Starting Material ◽  
Synthetic Route ◽  
Target Compound ◽  
Pharmacological Activities ◽  
Salvianolic Acid ◽  
Important Intermediate

Salvianolic acid B has many important pharmacological activities. A novel synthetic route of methyl acrylate derivative—an important intermediate to synthesize salvianolic acid B, was designed, and the target compound was prepared in seven steps of reactions with 2-bromo-3-hydroxy-4-methoxybenzaldehyde as major starting material. Its and other four important unreported intermediates’ structures were characterized by IR, 1H NMR, MS, etc.

Characterization of Five Oxidative Degradation Impurities and One Process Impurity of Suvorexant Drug Substance by LC-MS/MS, HR-MS and 1D, 2D NMR: Validation of Suvorexant Drug Substance and Process Impurities by HPLC and UPLC

2020 ◽  
Vol 58 (5) ◽  
pp. 433-444
Author(s):  
Nagaraju Rajana ◽  
Dharamasoth Rama Devi ◽  
Dinne Naresh Kumar Reddy ◽  
J Moses Babu ◽  
K Basavaiah ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Spectroscopic Data ◽  
High Performance ◽  
Oxidative Degradation ◽  
2D Nmr ◽  
Ultra Performance Liquid Chromatography ◽  
Drug Substance ◽  
Hplc Assay ◽  
Related Substance

Abstract During the oxidative (10% H2O2) degradation of suvorexant drug substance, around 1.0% of one impurity and less than 1.0% four impurities were found by a new high-performance liquid chromatography (HPLC) assay and related substance method. The mass numbers of 1.0% impurity was 469 [M + H]+, remaining four impurities were 172 [M + H]+, 467 [M + H]+, 483 [M + H]+ and 485 [M + H]+. The 469 [M + H]+, 485[M + H] and 172 [M + H]+ impurities were characterized by using the LC-MS/MS, HR-MS and 1D, 2D NMR spectroscopic data. The 172 [M + H]+ impurity was prepared synthetically and co-injected in HPLC. The retention time of synthesized 172 [M + H]+ impurity was matching with the unknown degradation impurity in HPLC. The developed mass compatible HPLC and ultra performance liquid chromatography methods were validated for drug substance and process impurities by following ICH Q2 (R1) guidelines.

scholarly journals Tri- and Tetrameric Proanthocyanidins with Dentin Bioactivities from Pinus massoniana

2020 ◽  
Author(s):  
Bin Zhou ◽  
Yvette Alania ◽  
Mariana Reis ◽  
Rasika Phansalkar ◽  
Joo-Won Nam ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Structure Determination ◽  
Hplc Analysis ◽  
Reference Data ◽  
Chemical Characterization ◽  
Pinus Massoniana ◽  
2D Nmr ◽  
Chiral Phase ◽  
Phytochemical Study

Guided by dentin biomechanical bioactivity, this phytochemical study led to the elucidation of an extended set of structurally demanding proanthocyanidins (PACs). Unambiguous structure determination involved detailed spectroscopic and chemical characterization of four A-type dimers (2, 4–6), seven trimers (10–16), and six tetramers (17–22). New outcomes confirm the feasibility of determining the absolute configuration of the catechol monomers in oligomeric PACs by 1D and 2D NMR. Electronic circular dichroism (ECD) as well as phloroglucinolysis followed by MS and chiral phase HPLC analysis generated the necessary chiral reference data.

scholarly journals Tri- and Tetrameric Proanthocyanidins with Dentin Bioactivities from Pinus massoniana

2020 ◽  
Author(s):  
Bin Zhou ◽  
Yvette Alania ◽  
Mariana Reis ◽  
Rasika Phansalkar ◽  
Joo-Won Nam ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Structure Determination ◽  
Hplc Analysis ◽  
Reference Data ◽  
Chemical Characterization ◽  
Pinus Massoniana ◽  
2D Nmr ◽  
Chiral Phase ◽  
Phytochemical Study

Guided by dentin biomechanical bioactivity, this phytochemical study led to the elucidation of an extended set of structurally demanding proanthocyanidins (PACs). Unambiguous structure determination involved detailed spectroscopic and chemical characterization of four A-type dimers (2, 4–6), seven trimers (10–16), and six tetramers (17–22). New outcomes confirm the feasibility of determining the absolute configuration of the catechol monomers in oligomeric PACs by 1D and 2D NMR. Electronic circular dichroism (ECD) as well as phloroglucinolysis followed by MS and chiral phase HPLC analysis generated the necessary chiral reference data.

Isolation and characterization of novel degradation products in cilnidipine by LC-QTOF-MS/MS, LCMSn, 2D-NMR and FTIR

2018 ◽  
Vol 42 (1) ◽  
pp. 634-646 ◽  
Author(s):  
Krishnam Raju Ch ◽  
Shanmukha Kumar J. V. ◽  
Sanath Kumar Goud Palusa
Keyword(s):  
Drug Discovery ◽  
Degradation Products ◽  
2D Nmr ◽  
3D Structures ◽  
Stress Studies ◽  
Isolation And Characterization

Comprehensive stress studies performed for cilnidipine established 3D structures for novel degradants CD1 and CD2, which may be useful for drug discovery activities.

Investigation and Characterization of New Impurity in Clorsulon Drug Substance

2018 ◽  
Vol 14 (4) ◽  
pp. 360-366
Author(s):  
Natarajan Sivanandham ◽  
Kempegowda Bommanadoddi Kempegowda
Keyword(s):  
Drug Substance

scholarly journals Synthesis and Biological Activity of New Brassinosteroid Analogs of Type 24-Nor-5β-Cholane and 23-Benzoate Function in the Side Chain

2021 ◽  
Vol 22 (9) ◽  
pp. 4808
Author(s):  
Nitza Soto ◽  
Karoll Ferrer ◽  
Katy Díaz ◽  
César González ◽  
Lautaro Taborga ◽  
...  
Keyword(s):  
Good Alternative ◽  
Positive Control ◽  
Starting Material ◽  
Chemical Structures ◽  
High Reaction ◽  
Similar Chemical ◽  
Synthetic Procedure ◽  
Hyodeoxycholic Acid ◽  
External Stresses

Brassinosteroids are polyhydroxysteroids that are involved in different plants’ biological functions, such as growth, development and resistance to biotic and external stresses. Because of its low abundance in plants, much effort has been dedicated to the synthesis and characterization of brassinosteroids analogs. Herein, we report the synthesis of brassinosteroid 24-nor-5β-cholane type analogs with 23-benzoate function and 22,23-benzoate groups. The synthesis was accomplished with high reaction yields in a four-step synthesis route and using hyodeoxycholic acid as starting material. All synthesized analogs were tested using the rice lamina inclination test to assess their growth-promoting activity and compare it with those obtained for brassinolide, which was used as a positive control. The results indicate that the diasteroisomeric mixture of monobenzoylated derivatives exhibit the highest activity at the lowest tested concentrations (1 × 10−8 and 1 × 10−7 M), being even more active than brassinolide. Therefore, a simple synthetic procedure with high reaction yields that use a very accessible starting material provides brassinosteroid synthetic analogs with promising effects on plant growth. This exploratory study suggests that brassinosteroid analogs with similar chemical structures could be a good alternative to natural brassinosteroids.

scholarly journals Novel Experimental Study of Fabric Drying Using Direct-Contact Ultrasonic Vibration

2018 ◽  
Vol 11 (2) ◽  
Author(s):  
Viral K. Patel ◽  
Frederick Kyle Reed ◽  
Roger Kisner ◽  
Chang Peng ◽  
Saeed Moghaddam ◽  
...  
Keyword(s):  
High Frequency ◽  
Direct Contact ◽  
First Generation ◽  
Scale Up ◽  
Enthalpy Of Vaporization ◽  
Piezoelectric Transducers ◽  
Scaling Analysis ◽  
Moisture Removal ◽  
Low Efficiency

Abstract Fabric drying is an energy-intensive process, which generally involves blowing hot dry air across tumbling wet fabric to facilitate evaporation and moisture removal. Most of the energy supplied is used to overcome the enthalpy of vaporization for water. Although this process tends to be inefficient, it is fairly simple and forms the basis for the majority of existing clothes dryer technology today. To address the relatively low efficiency, a new method of drying called “direct contact ultrasonic fabric drying” is proposed. The process involves using high-frequency vibration introduced by piezoelectric transducers, which are in contact with wet fabric. The vibration is used to extract water droplets from the fabric mechanically. In this study, a total of 24 individual transducers are used in a module to dry a 142 cm2 sized fabric. The performance characterization of this single module has enabled successful scale-up of the system to a midscale prototype dryer, which can be used to ultrasonically dry clothing-sized fabric (∼750 cm2). The first-generation ultrasonic fabric dryer fabricated uses as little as 17% of the energy needed by traditional evaporation-based drying techniques. In addition to experimental data, this paper presents the results of a kinetic and scaling analysis that provides some important insights into ultrasonic drying.

Sign in / Sign up

Export Citation Format

Share Document