Chromatographic studies of unusual on-column degradation of cefaclor observed in the impurity separation by HPLC

The Synthesis of Warfarin Using a Reconfigurable‐Reactor Platform Integrated to a Multiple‐Variable Optimization Tool

“…The portion is blindly sent to a second‐dimension column for the analysis of a second CQA of the target analyte. The second CQA measurement, which plays an instrumental role in deciding whether synthetic conditions under investigation are worth pursuing further, could be erroneous if the target analyte undergoes chemical degradation during analysis [8, 9] . The evidence of such an analytical artefact is vital information that dictates the validity of the second CQA measurement.…”

“…The second CQA measurement, which plays an instrumental role in deciding whether synthetic conditions under investigation are worth pursuing further, could be erroneous if the targeta nalyte undergoes chemicald egradation during analysis. [8,9] The evidence of such an analytical artefact is vital information that dictates the validity of the second CQA measurement. Currentp ractice in high throughput screening of asymmetricr eactionc onditions turns ab lind eye to such possibilities during conventional2Da nalysis.…”

Actual Process Impurity or an Analytical Artifact? A Case Study Involving Conversion of Amide to Nitrile to Uncover the Truth and Mitigate

“…Zhong et al documented an atypical oxidative decarboxylation of cefaclor, resulting in the generation of an impurity similar to cefaclor on the highperformance liquid chromatography (HPLC) column during analysis. 5 Similarly, Wang et al documented the occurrence of on-column formation of azo and hydrazo dimer impurities from aniline analytes when using an XBridge shield RP18 column under basic pH conditions. 6 Effective control and elimination of impurities during the synthetic process can be achieved by implementing the appropriate control strategy provided that they are accurately reported during process monitoring.…”

“…While the examples provided pertain to known chemical reactions, there are instances where the formation of such artifact impurity peaks requires comprehensive investigation to grasp the underlying cause and mechanism behind their occurrence. Zhong et al documented an atypical oxidative decarboxylation of cefaclor, resulting in the generation of an impurity similar to cefaclor on the high-performance liquid chromatography (HPLC) column during analysis . Similarly, Wang et al documented the occurrence of on-column formation of azo and hydrazo dimer impurities from aniline analytes when using an XBridge shield RP18 column under basic pH conditions .…”

Intelligent Multidimensional Purity Analysis and Confirmation Tool for Multiple Attribute Analysis

“…In the absence of on-column degradation, the process parameters get the attention. Analytical conditions, which often include mobile phases consisting of a wide range of pH buffers, can indeed trigger chemical degradation or racemization when the chiral center in the analyte is vulnerable to acidic or basic conditions. − On-analysis artifact investigations are largely overlooked because such studies are often deemed cost-prohibitive, especially in early phase drug development. What is needed is an LC configuration that allows chemists to recirculate an analyte through the same LC column and assess its on-column stability in addition to performing orthogonal multidimensional analysis from a single injection.…”