Unprecedented High Throughput Titration by Feedback-Based and Subsequent Fixed Triangular Wave-Controlled Flow Ratiometry and Its Application to Quantification of Japanese Pharmacopoeia Drugs

Abstract

Throughput rate of flow ratiometric titration has further been enhanced by shortening the lag time from the confluence of solutions upstream to the sensing of signal downstream and by optimizing analytical parameters. Feedback-based upward and downward scans of titrand/titrant flow ratio were repeated in order to offset the effect of the lag time and thus to locate the equivalence point. Subsequent faster fixed triangular wave-controlled scans in narrower range further increased the throughput rate. Analytical parameters such as scan rate and scan range were optimized. Maximally, 46.9 titrations/min was realized with reasonable precision (RSD = 1.79%). Applicability of the method to the quantitation of the Japanese Pharmacopoeia drugs (furosemide, isoniazid and prochlorperazine maleate) was verified, where the latter two drugs were determined by nonaqueous titrations.