关键词：
GAC
In-line monitoring
Off-line monitoring
Ipratropium bromide
Ion-selective electrode
Calix[6]arene
HPLC
Hydrolysis kinetics
摘要：
"Green analytical chemistry" (GAC) is a vital area towards the concept of sustainability. As a consequence of the widespread application of HPLC in drug-related analytical investigations and the resulting contamination of the environment with organic solvents questions have been raised about the toxicity/greenness of HPLC in the ecosystem. Traditional analytical separation technologies yield approximately 50 mL of waste per analytical data point. To this end, the pharmaceutical community continues to search for greener opportunities to markedly reduce the amount of organic waste produced and move from conventional offline separation based methodologies to greener in-line alternatives. In this contribution, we're adopting a "Just-Dip-It" approach with the ultimate goal of advancing and exploiting the potentiometric sensors to their most effective use in different disciplines of drug development. The unique abilities of these ion-selective electrodes (ISEs) for in-line measurements is the key driver for adoption of GAC principles to improve environmental friendliness of the analytical methods. For a meaningful comparison, this work compares the organic waste resulting from ISEs versus HPLC for degradation kinetics monitoring of active pharmaceutical ingredients (APIs) with respect to the 12 principles of GAC. Ipratropium bromide (IP) was chosen as a hydrolyzable anticholinergic drug, and its degradation kinetics were monitored by the two techniques. The first in-line strategy is attained by dipping a highly integrated IP membrane sensor for continuous monitoring of the hydrolysis kinetics of IP by tracing the emf decline over the time scale. The second off-line strategy utilizes a separation-based chromatographic HPLC method via discontinuous tracking the decrease of IP peak area spectroscopically at 220 nm over time. The advantages and shortcomings of each strategy considering GAC principles are highlighted. The merits of these benign real-time analyzers (ISEs) that
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