Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol
Neeraj Kumar1, Subba Rao Devineni1, Prasad Reddy Gajjala1
1Chemical Research Department, Micro Labs Ltd, API Division, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India.
Abstract:
One unknown impurity (Imp-II) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2-ylamino)ethyl]benzene-1,2-diol (Imp-II) using the liquid chromatography--mass spectrophotometry (LC--MS) analysis. Imp-II was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C, DEPT (1D NMR), HSQC (2D NMR) and infrared spectroscopy (IR), and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification, the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit<0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details.
Related Concept Videos
01:12Electrospray Ionization (ESI) Mass Spectrometry
ESI utilizes electrical energy to transfer ions from the liquid phase of the sample into the...
01:19Cyclic Processes And Isolated Systems
In the case of a non-isolated system, the change in the internal energy is zero only if the process is cyclic. A thermodynamic process is considered cyclic if the system undergoes a series of changes and returns to its initial state.
Consider a cyclic process that returns to its initial state, undergoing a four-step process. The heat transfer along each...
01:15Dehydration Synthesis
Dehydration synthesis (also called a condensation reaction) is the chemical process in which two molecules covalently link together to form a new molecule, along with the release of a water molecule. Many physiologically important compounds form by dehydration synthesis reactions, such as complex carbohydrates, proteins, DNA, and RNA.
Synthesis of carbohydrates
Sugar molecules are covalently linked together by dehydration synthesis. During the reaction, the hydroxyl (-OH) group from...
01:59Lagging Strand Synthesis
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
01:04¹³C NMR: ¹H–¹³C Decoupling
A broadband decoupling technique is used to simplify these complex, sometimes overlapping, signals. Broadband decoupling relies on a...
02:36Transfer RNA Synthesis
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...