High-Throughput Photometric Titrimetry Based on a Feedback-based and Subsequent Fixed Triangular Wave-controlled Flow Ratiometry

Abstract

Titrimetry is a classical analytical method that is still widely in use. It is adopted, for example, as a method for the quantitative analysis of nearly 60% of drugs listed in Part 1 of the Japanese Parmacopoeia. 1 According to a book by Szabadváry, 2 the origin of titrimetry can be traced back to 1729 when Geoffroy analyzed vinegar samples with K2CO3. However, conventional manual titration using glassware, such as a burette, is tedious and time-consuming. Various flow titration techniques have therefore been developed, as recently reviewed by Tanaka and Nakano. 3These include flow injection titration, 4 sequential injection titration, 5 triangle programmed coulometric titration, 6-8 flow ratiometric titration 9,10 and monosegmented flow titration. 11 Tanaka et al. 12,13 proposed a feedback-based flow ratiometry, a new concept for continuous titration. In their approach, the titrant flow rate is linearly varied while the total (titrant + titrand) flow rate (FT) is held constant. The scan direction of the titrant flow rate is reversed from upward to downward, and vice versa, whenever the equivalence point EP is detected. Thus, the scan range is limited to the range around EP. A high throughput was attained for photometric 12 and potentiometric 13 titrtions (6 and 5 titrations per minute, respectively). Jo and Dasgupta 14 applied this method to cheletometric titrations.Very recently, we introduced a new strategy to feedback-based flow ratiometry. 15 After feedback-based operation, fixed triangular waves were used to control the titrant flow rate in order to further limit the scan to the range of interest. The developed method realized potentiometric titrations having an extremely high throughput rate at reasonable precision (maximally 17.6 titrations per minute at RSD = 0.35%). In the present study, we extended the principle of the method to photometric titrimetry, because the photo-sensor is one of the most popular detectors in flow analyses, and is expected to have a quicker response than an electrode. ExperimentalFlow system Figure 1 shows the flow system of the present study. The principle of flow ratiometry for high-throughput titration, which we recently proposed for potentiometric titration, was extended to photometric titration. The flow rate (FB) of a base solution containing an acid-base indicator was linearly varied in response to a control voltage (Vc) generated from a computer. With the total (acid + base) flow rate (FT) being kept constant, the base solution was merged with an acid solution, which was aspirated to the confluence point at a flow rate of FT -FB. Downstream, the relative transmittance of the mixed solution was measured at the maximum absorption wavelength of the base form of the indicator. Initially, a feedback-based control was applied, where the scan direction of Vc was reversed from upward to downward, and vice versa, whenever the transition of the indicator at the equivalence point (EP) was sensed. Next, the scan range of Vc was further limited to the range just around EP by using f...

Introduction of Air-Segmentation Approach to Flow Titration by Feedback-based and Subsequent Fixed Triangular Wave-controlled Flow Ratiometry

“…The principle of feedback-based and subsequent fixed triangular wave-controlled flow ratiometry was described in detail before. [23][24][25] Therefore, the following is a brief description on the principle; a detailed description is provided in Supporting Information ( Fig. S1 and its caption).…”

“…On the other hand, the time needed per titration is proportional to the Vc scan range and inversely proportional to the Vc scan rate in the Fxd mode. [23][24][25] The higher the scan rate, the shorter the time per titration is. The determination coefficients (r 2 ) for the linear regression line of time/titration vs. the reciprocal of Vc scan rate were 0.996 and 0.999 for the titrations of HCl and CH3COOH, respectively, and in accordance with the theory.…”

“…The determination coefficients (r 2 ) for the linear regression line of time/titration vs. the reciprocal of Vc scan rate were 0.996 and 0.999 for the titrations of HCl and CH3COOH, respectively, and in accordance with the theory. [23][24][25] Although higher throughput rate could be achieved when the Vc scan rate was 400 mV s -1 , 200 mV s -1 was selected because it gave more precise results. optimized condition (i.e., 15 rpm).…”

“…Aydan et al 22 simultaneously determined magnesium and calcium ions by a feedback-based flow ratiometry using a photosensor and an ion sensor that were set in series in a flow system. Tanaka et al [23][24][25] further enhanced the throughput rate of flow ratiometry by combining a feedback-based control with a subsequent fixed triangular wave control that scanned narrower range with higher rate. Miyazaki et al 26 realized unprecedented throughput rate of 46.9 titrations/min (1.28 s/titration) by applying this concept.…”

Analytical Parameters for Amplitude-Modulated Multiplexed Flow Analysis

“…More recently, the method was further improved with respect to throughput rate (maximally, 34 determinations/min) through the introduction of a fixed triangular wave control approach for faster and narrower-ranged scans. [6][7][8] These approaches brought us a new concept of flow analysis that utilized the principles of communication using waves (i.e., modulation, multiplexing, demodulation, etc.). We named the method amplitude-modulated multiplexed flow analysis (AMMFA) and published details in a previous paper.…”