JPH0772732B2 - Quantitative determination of titration equivalence points of at least two independent titratable species by single sample flow injection analysis - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION INDUSTRIAL FIELD OF APPLICATION The present invention relates to a novel apparatus and method for improved flow-injection titration analysis.

<Prior Art> The demand for reproducible and accurate chemical analysis methods continues to increase in the fields of medicine, agriculture, and pharmacy. Various analyzers have been made to meet this demand. For each new analyzer, the focus is on the construction of equipment that increases the analytical capacity and reduces the number of steps required in the analytical method.

Flow-injection analyzers are designed to meet these demands. Such an analyzer is a device capable of detecting the characteristics and components of a sample injected into a continuously flowing solution. Flow injection method
nalysis) is based on an analyzer capable of forming a reproducible gradient of a sample in a reagent stream that can be detected as a gradient curve. The measurements performed on the resulting gradient curve are used to quantify the properties and components of the sample.

A new area of flow injection method is the combination of the best features of flow injection method with titration technology.
(FIT)] field. FIT is derived from titration, which is a quantitative determination of the components of a known volume of a solution, with a standard reaction solution of known strength being added gently until the reaction is complete. Completion of the reaction is often indicated by a change in color of the solution (indicator) or an electrochemical change.

FIT is developed for process control applications to create fast, easy, reliable, versatile and accurate analytical instruments. Unlike other flow acquisition methods, FIT is based on peak width rather than peak height. In contrast to other flow-injection analysis methods, FIT utilizes large sample dispersions that create concentration gradients over time. The width of this concentration gradient is proportional to the logarithm (log) of the sample concentration. This concentration gradient is known as the "exponential concentration gradient". This exponential concentration gradient is the concentration gradient in the mixing chamber during flow-in analysis.

The concept of single-point titration using flow-in analysis is based on the Analytica Ch
Imica Acta) Volume 105 (1979), pages 67-75, by Ove Astrom, "Single-Point Tities".
trations) ", the acid / base system is described.
Astrome's method for single point titrators for acids and bases is a reference electrode, glass electrode, 300 cm long mixing coil,
And a reaction cell consisting of Teflon injection pipe is used. Only one analysis can be performed using a reaction cell with detection electrodes. The need for a dual analytical device has been felt for many years.

A multi-component trace component analyzer using non-resolved continuous flow analysis is known as "Correspondence", "Analytical Chemistr".
y), Vol. 50, No. 4, (1978) pp. 654-656. However, this analytical method is taught only in a very general way. Multi-component trace analysis of compounds 4- (2-pyridylazo) resorcinol (PAR), lead (II) and vanadium (V) using unresolved continuous flow is a colorimetric rather than a titration method. FI
No specific teachings have yet been found for multiple component trace analysis using T, especially for caustic / carbonate systems.

The instruments used for multi-component trace component analysis generally include reaction cells, measuring instruments and recorders or data processors, Analytika-Simica Actors.
ica Chimica Acta), 109 (1979), pages 1-24, Pungor, et al., "Indigestion technic in dynamic flow-
Through Analysis Electro Analytical Sensors (Injection Technique In Dynamic Flow-Throu
gh Analysis With Electroanalytical Sensors) ”, this device cannot serve as both a reaction cell and a detection cell for multi-end point FIT. The present invention provides such a device and its associated FIT method. It is an object.

Known analytical methods utilize batch analysis methods for endpoint detection of independently titratable species during caustic / carbonate reactions. Scotts Standard Methods of Chemical A
nalysis) (5th edition, p. 2256), one batch method is that the double endpoint measurement of sodium hydroxide and sodium carbonate is (a) phenolphthalein endpoint (NaOH
NaHSO ₄ and H ₂ O; NaCO ₃ to NaHCO ₃ ) and (b) methyl orange endpoint (NaHC
Conversion of O ₃ into NaHSO ₄ , CO ₂ and water) with sulfuric acid. However, the batch method has many drawbacks, as it does not allow continuous quantitative measurement or continuous titration analysis. Batch titration should be stopped periodically and the reactor should be cleaned after each reaction is complete. This known analytical method requires a long analysis time to obtain the required results. Therefore, there is a need for multiple endpoint measurement of independently titratable species in a continuous flow, non-batch type titrator.

The known continuous flow analysis method is
J.Ruzicka, and E.
H.Hansen), Flow Ingestion Analysis,
Wheelie-Interscience Hub Reproduction (Chemical Analysis, Volume 62), 1981 [Flow Injecti
on Analysis, Wiley-Interscience Publication, (Chem
ical Analysis, Vol. 62), 1981] and has been developed for continuous flow acid-base titration.

The problem with the single channel Ruzicka instrument is that the results were limited to single component analysis. To overcome this problem, Lucika and Hansen (Ruzicka an
d Hansen) is “Recent Daviroments in Flow In-Execution Analysis: Gradient Technics and Hydrodynamics.
"Ingestion", Analytical Shimika Actor ["Recent Developments in Flow Injection Analysi
s: Gradient Techniques and Hydrodynamic Injection ",
Analytica Chimica Acta], Volume 145 (1983), Volume 1-1
Another titrator, described on page 5, was developed. However, this continuous flow multiple endpoint titrator is limited to teachings for single component acid-base titration. In particular, the author focuses on titration of phosphoric acid with 1 × 10 ^-3 M sodium hydroxide,
Multi-component flow acquisition multiple end-point devices are not intended.

Another flow-in-exclusion titration method is the US patent.
No. 4,283,201 (DeFord et al.), In which the titrant is supplied to two parallel fluid communication circuits.
The DeFord teachings provide methods and apparatus for FIT using multiple reaction streams, analyzers and detectors for multiple endpoint detection of complex samples. This teaching does not meet all the requirements of the medical, pharmaceutical and agricultural fields for analytical devices. There is a need for a flow acquisition analysis method that requires less equipment and less time than the teachings of Defode, and provides data on multiple endpoints. There is a long-felt need for methods and apparatus for performing multiple endpoint titrations in a single assay. The present invention overcomes these teachings and aims to provide a non-linear multiple endpoint FIT for several species of samples.

DETAILED DESCRIPTION OF THE INVENTION The present invention is a method for detecting the end point or equivalence point for independently titratable species (s) for a non-batch, continuously flowing reactant, particularly a caustic / carbonate titration system. I will provide a.

More specifically, the present invention provides a stream of carrier liquid that flows at a substantially constant flow rate and that contains a substantially constant concentration of a single reagent; introducing a multi-component sample into the carrier stream; Flow into a mixing and detection chamber at a controlled flow rate; a process of forming an exponential dilution gradient in the mixing and detection chamber, each step of the sample mixture in a single reaction at multiple equivalence points in the mixing chamber And titrating the concentration of each species of the sample in the mixing chamber by forming a relationship between the titration times to the equivalence point of each species. A method for quantifying titration equivalence points of at least two independent titratable species is provided by flow-injection analysis of a sample.

This method requires at least 2 to obtain multiple equivalence points.
Step of using a single acid / base neutralization reaction.

Alternatively, the method of the invention further comprises the step of using at least two reduction or oxidation reactions to obtain multiple equivalence points.

The apparatus used in the present invention comprises a main chamber having an inlet hole and an outlet hole, a gas trap for collecting bubbles formed when the fluids are mixed in the main chamber, and a gas trap arranged adjacent to the gas trap in a mixing cell. A dual chambered mixing cell with a detector for the equivalence point detection of independent titratable species; a detection device arranged in the mixing cell; and in the mixing cell arranged in the mixing cell A mixing device for mixing the fluid to produce only turbulent flow; and a device for measuring titration equivalence points of at least two independent titratable species by flow-in-exclusion analysis.

In the present invention, an "exponential dilution gradient" is formed by introducing a sample into a fluid stream flowing through a mixing chamber. The concentration of the sample in the liquid in the mixing chamber is highest when the sample is first introduced into the mixing chamber and mixed with the liquid in the mixing chamber. As the liquid stream flow continues to flow through the mixing chamber, the concentration of sample in the mixing chamber decreases over time. This decrease in sample concentration in the mixing chamber per unit time is initially maximal and then becomes smaller as the sample is swept from the mixing chamber by the fluid flow flowing through the mixing chamber.
This decrease in concentration over time is the dilution gradient. This dilution gradient is an exponential dilution gradient, since it is initially maximal and then progressively smaller.

The term "independent" in "at least two independent titratable species" is "discrete or different".
It means that. For example, sodium hydroxide and sodium carbonate are separate titratable species. In other words, sodium hydroxide and sodium carbonate are different titratable species. Examples of non-independent or separate or non-differentiable titratable species are sodium carbonate and sodium bicarbonate. This is because sodium carbonate forms sodium bicarbonate when titrated.
On the other hand, when titrating sodium hydroxide with hydrochloric acid,
It produces sodium chloride, not sodium carbonate. Therefore, sodium hydroxide is an independent or separate or different species from sodium carbonate.

Detailed Description of Embodiments One method of determining the concentration of each species in a sample in a mixing chamber by forming a relationship between the titration times to the equivalence point of each species is shown by the following equation: It is: t ₁ = Vm / Q [lnVs / Vm) −lnC _t ] + Vm / Qln (C ₁ + C ₂ ) (1
5) and _{t 2 = Vm / Q [ln} (Vs / Vm) -lnC t] + Vm / Qln (C 1 + 2C 2)
(16) where t ₁ is the time to the equivalence point of the first species; t ₂ is the time to the equivalence point of the second species; Vs is the sample volume; Vm is the mixing cell Is the volume; Q is the flow rate; C ₁ is the molar concentration of the first species; and C ₂ is the molar concentration of the second species.

Exponential function when a sample plug with concentration Cs is injected into a flowing titrant stream with concentration Ct and then enters the mixing chamber, and when the mixing and chemical reaction is instantaneous A concentration gradient is formed. The exponential concentration gradient of the sample and titrant mixture then goes to the detector, where two or more signal transitions are obtained. These signal transitions are points at which the discontinuous flow portions show a remarkable change from acidic to basic and from basic to acidic, respectively. The first signal change indicates the passage of the titration equivalence point described by a sharp change in carrier pH; and, in the case of a single titration species, the end of titration. These abrupt pH changes can be readily detected colorimetrically by using a pH indicator or electrochemically by measuring pH. Other titratable species can be detected using similar methods [eg, ion-selective electrodes or amperometric titrators].

Equations (15) and (16) above differ from each other only in the last term. That is, the last term in equation (15) is "(C ₁ +
C ₂ ) ”, the last term of equation (16) is“ C ₁ + 2C
₂ ". Therefore, t ₂ is always larger than t ₁ as shown in Table 1. The terms used in equations (15) and (16) are defined immediately after equation (16). The unknowns in Eqs. (15) and (16) are C ₁ and C ₂ . Everything else is known. Therefore, it is easy to determine the _two unknowns C ₁ and C ₂ from the two equations (15) and (16).

It was not possible in the prior art to determine two independent species by measuring the titration times (t ₁ and t ₂ ) to _two equivalence points. This is because in the prior art, only titration times up to a single equivalence point were used. 2 with conventional technology
When it was desired to determine two independent species, a colorimetric determination was made by measuring the% transmission at two wavelengths. The present invention is superior to these conventional methods in the following points. That is, the present invention can be used to determine more than one species, the present invention does not use, and is not limited to, a relatively narrow range of colorimetric agents, instead of a wide range of sleds. Titration reagents such as acid / base titration reagents and oxidation / reduction titration reagents can be used.

One aspect of the device of the present invention is shown in FIGS. The device has a double chambered mixing cell having a housing 12 and a cavity 14 in the housing. Stirrer 16 placed in cavity 14
There is. The detection device may be a colorimetric detector, which is then electrically connected to either an amplifier or a recording device. The housing 12 is preferably constructed with a gas trap 24 located near the exit hole 20. The gas trap 24 essentially has a second cavity in the housing and a cavity 14
It is formed in order to trap the bubbles formed during the multi-end point titration. Cavity 14 is a structure that provides turbulence in the carrier / sample flow, while gas trap 24 is a structure that provides laminar flow and collects and contains any bubbles formed during the reaction. The trap 24 abuts the top of the cavity 14 and prevents gas from being trapped and left in the cavity 14 and disrupting the titration measurement being performed. The outlet hole 20 can be located at any point between the bottom and top of the gas trap, but is preferably located near the top as shown in FIG.

Typical results for a caustic / carbonate system using the method and apparatus of the present invention are the following multi-component system; Table 1 and FIG.
Indicated by. Where Cs = sample concentration, Ct = titrant concentration, R = sample volume / cell volume ratio, T = average cell residence time of titrant, and T _1n (RF _i ) = t _i + T _1n Ct (17) , t _i = time to equivalence point i, and Fi = sample concentration function).

Corresponding to the equivalence point i, and then the caustic / carbonate system: And for the titrated species at time t ₁ : Then, it has been for the species titration at time t _2: n ₁ mole of NaOH (concentration = C ₁₎ n ₂ moles of Na ₂ CO ₃ (concentration _{= C 2) F 2 = C} 1 + 2C 2 n 2 moles of Na ₂ CO ₃ (equivalent to the concentration of C ₂ ) Tln R + Tln F _i = t _i + Tln Ct t _i = T (ln R−ln Ct) + Tln F _i = a + b ln F _i t ₁ = a + b ln (C ₁ + C _{2 ) t 2 = a + b ln} (C 1 + 2C 2) C 1 + C 2 = ln -1 (t 1 / b-a / b) = K 1 C 1 + 2C 2 = ln -1 (t 2 / b-a / b _{) = K 2 C 2 = K} 2 -K 1 C 1 = K 1 -C 2 = K 1 - (K 2 -K 1) = a 2K ₁ -K _2, and the device constants used; C _t = 0.001 mol / R = 0.0816, T = 4.57 min. Found from the measurement of.

The following data examples are summarized in Table 1, where the sample size (Vs) was 1.05 ml. Cell volume (Vm)
Was 12.87 ml and the flow rate (Q) was 2.8 ml / min.

The concentration C ₁ is mol / min and the time is minutes.
The linear relationship of this multiple end point system is illustrated in FIG.

While the invention has been described with respect to quantitation and evaluation in relation to the principle of equivalent weight, the scope of the invention is defined by the claims.

[Brief description of drawings]

FIG. 1 is a schematic diagram of a preferred embodiment of the device invention. 2 is a cross-sectional view of the embodiment of FIG. 1 taken along line 2-2. FIG. 3 is a graphical representation of the data obtained by the method of the present invention.

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Claims (3)

[Claims] 1. A flow of a carrier liquid flowing at a substantially constant flow rate and comprising a substantially constant concentration of a single reagent; introducing a multi-component sample into the carrier flow; the sample being defined. Flowing through the mixing and detection chamber at a flow rate; forming an exponential dilution gradient in the mixing and detection chamber, each step of each species of sample mixture in the mixing chamber at multiple equivalence points with a single reactant. A single sample, characterized in that the concentration of each species of the sample in the mixing chamber is determined by forming a relationship between the titration times to the equivalence point of each species. Determination of titration equivalence points of at least two independent titratable species by flow infusion analysis of. 2. At least 2 to obtain a plurality of equivalence points
The method of claim 1 further comprising the step of using a single acid / base neutralization reaction. 3. At least 2 to obtain a plurality of equivalence points
A method according to claim 1 including the step of using individual reduction or oxidation reactions.