JP2760282B2 - Calibration solution for ion-electrode method electrolyte analyzer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0000]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to N in body fluids such as blood and urine.
The present invention relates to a calibration solution used for a clinical electrolyte analyzer by a dilution method using an ion electrode for measuring a ⁺ , K ⁺ , and Cl ^- ion concentrations.

[0001]

BACKGROUND OF THE INVENTION for clinical using ion electrodes having selectivity for ions Na ⁺ / K ⁺ / Cl ^- analyzer is mainly used for analysis of urine and blood (serum). Calibration is essential for ion electrodes and must be performed at least twice a day. This is because the output of the ion electrode changes due to deterioration due to temperature change, contamination, and the like, and calibration is usually performed at two types of concentrations.

[0002] Calibration solutions emphasize three points: that two kinds of calibration concentrations have an appropriate interval, that the pH is near neutrality (pH 6 to 8), and that the ionic strength is not much different from that of the sample. It is decided. The ionic strength is adjusted to 120 to 180 mmol / l which is close to the ionic strength of serum. For ^{example, Na + / K + / Cl} -
For example, the first point is set to around 140/4/100, which is the standard value of serum, and the second point is set to 100/8/60, 120/10/70, or 16
By setting 0/6/140 or the like, the setting is made so that the ionic strength is not largely changed between the two calibration solutions.
The reason why the ionic strength is not largely changed is that if the ionic strength increases or decreases, the activity coefficient of the target ion changes, and an error occurs when converted into a concentration.

The output E of the ion electrode is expressed as follows by the Nernst equation. _{E = E 0 + (RT /} zF) lna M = E 0 + Nloga M ...... (1) where the activity of a _M is M ion, N is the in Nernst constant is 59.15mV at 25 ° C.. Note that this equation is 1
This is the case for a positive cation. Activity is activity coefficient f × concentration C
Therefore, E = E ₀ + Nlogf + NlogC _M (2) Nlo in the calibration solution-sample system with almost the same activity coefficient
Since gf is considered to be a constant, E = E ₀ '+ NlogC _M (3) That is, as shown in FIG.
And C2 are calibrated, a calibration curve is drawn, and the concentration Cx is calculated from the detection potential of the sample of unknown concentration x. This is a conventional calibration and measurement system, and the concentration is calculated by the following equation regardless of the dilution method or the non-dilution method.

(Equation 2)

[0004] By the way, the concentration range of target ions differs greatly between blood and urine. Especially for K ⁺ , the concentration in blood is 3
６6 mmol / l, whereas urine is 10-100
mmol / l. For this reason, it is said that even if calibration is performed at the blood level, the values do not match at the urine level, and two types of calibration solutions are prepared for blood and urine, and calibration is performed.

[0005]

If different calibration liquids are used for blood and urine, the number of calibration steps is doubled. Ion electrodes require many calibrations, so
The burden on the worker also increases accordingly. Therefore, studies were conducted on whether a common calibration solution could be prepared for blood and urine.

Regarding the reason why the values do not match when urine is measured using an ion electrode calibrated in the blood mode, the response speed of the electrodes is different because the concentration ranges are different between blood and urine conventionally. There is a theory that this is due to the fact that there is a difference in ionic strength and the like due to a difference in the matrix of the sample. However, as a result of studying without being bound by these theories, the present inventor found that the selectivity of the ion electrode had a large effect, and that the concentration of the blood-level calibration solution was inappropriate. It was also found that urine with greatly different interfering ion concentrations fluctuated greatly. An object of the present invention is to provide a calibration solution capable of preparing a calibration curve applicable to both blood measurement and urine measurement.

[0007]

SUMMARY OF THE INVENTION The present invention relates to a calibration solution for a clinical electrolyte analyzer using a dilution method using an ion electrode, wherein the first calibration solution of two types of calibration solutions is human serum. When the concentration of one target component in the calibration solution at the second point is C _MC2 , the concentration C _NC2 of an ion that becomes an interfering ion with respect to the target ion is defined as

(Equation 3) It was near. Here, those K _MN is considered near worst value in the selected coefficient of the interfering ions to target ions, C _MC1
Is the target ion concentration of the first calibration solution, C _NC1 is the interfering ion concentration of the first calibration solution, C _X is the concentration of the target ion near the upper limit of the normal value or the upper limit of the measurement range at the urine level, C _NX
Is the concentration near the normal value of interfering ions at urine level.

[0008]

In the ion electrode, the response to ions other than the target ion, that is, interference is inevitable to some extent. The electrode potential E when there is interference is given by Eisenman-Ni
It is represented by the colsky formula. E = E ₀ ′ + Nlog (C _M + K _MN C _N ) (6) K _MN is a selection coefficient, and equation (6) is obtained by converting the activity into a concentration, the target ion concentration C _M and the interfering ion. Both concentrations C _N are monovalent cations. The most disruptive in blood and urine are usually K ⁺ for the Na electrode, Na ⁺ for the K electrode, and HCO ₃ ⁻ for the Cl electrode. If each selection coefficient is close to 0, equation (6) becomes substantially the same as equation (3), and no problem occurs. However, the selection coefficient K _MN is not actually 0, and K ⁺ , Na ⁺ , Cl ⁻
Due to the characteristics of the PVC film type electrode used for the electrode, the sensitive substance and the plasticizer flow out of the film during use, gradually deteriorate, and the selectivity tends to increase. Therefore, when the calibration is performed in the same manner as in FIG. 1 and the sample is measured, the calibrating solution and the sample both contain an interfering substance.
The measured value will deviate from the true value.

In consideration of interfering substances, the calibration curve and the measurement are shown in FIG. Here, C _MC1 is the target ion concentration in the calibration solution 1, C _NC1 is the interference ion concentration in the calibration solution 1, C _MC2 is the target ion concentration in the calibration solution 2, and C _NC2 is the interference ion concentration in the calibration solution 2. , C _NX is the concentration of interfering ions in the sample.

From the relationship shown in FIG. 2, the true value C _X is expressed by the following equation (7).

(Equation 4) However, since the actual calculation is performed by equation (4), the difference is an error. To reduce the error, (4)
And C _X, which is calculated by the formula, as long (7) C _X is the same that is calculated by the formula. Therefore, from equation (4)

(Equation 5) So, substitute this into equation (7)

(Equation 6) Get. When this equation is solved for C _NC2 , the following equation shown in equation (5) is obtained.

[0011]

(Equation 7) That is, one of the two calibration solutions is determined to have a concentration near the normal value of serum (C _MC1 , C _NC1 ), and C _X is near the upper limit of the normal value of the target ion at the urine level or near the upper limit of the measurement range. The concentration, C _NX, is the concentration near the normal value of interfering ions at the urine level, and the worst selectivity is assumed as the selection coefficient K _MN , and the target ion concentration (C _MC2 ) of the second calibration solution is determined in the urine. Choosing an appropriate concentration determines the optimal interfering ion concentration (C _NC2 ) to be contained therein.

The calculation is actually performed by applying numerical values. The concentration of the calibration solution 1 was set to the same value as the normal value in blood, and Na ⁺ /
K ⁺ / Cl ⁻ / HCO ₃ ⁻ is 140/4/100/25 (m
mol / l). The selection coefficient K _MN is assumed to be K _{Na, K} = 0.02 to 0.2 K _{K, Na} = 0.001 to 0.01 K _Cl, HCO3-= 0.05 to 0.2 Use numerical values. It is assumed that the point where the measured concentration values match in the urine sample with and without the effect of interfering ions is Na ⁺ / K ⁺ / Cl ⁻ = 400/50/400. Also, the normal value of interfering ions in urine was calculated as K ⁺ / N
Assume a ⁺ / HCO ₃ ⁻ = 40/100/0. These values are empirically assumed from actual urine measurements, and it is easy to change the values within an acceptable range.

FIGS. 3A to 3C show graphs calculated by a computer under these conditions.
(A) is the allowable concentration range of the interfering ion K ⁺ with respect to the Na ⁺ concentration, (B) is the allowable concentration range of the interfering ion Na ⁺ with respect to the K ⁺ concentration, and (A) is the interfering ion HCO _{3 with} respect to the Cl ⁻ concentration. ^- represents the acceptable concentration range of,
The Δ mark and the + mark represent a width of ± 1%. Therefore, if the calibration liquid is adjusted so as to have the disturbing ion concentration in the region sandwiched between the curves of both marks, the optimum concentration of the calibration liquid is obtained. The assumed numerical values are close to actual ones, but it is easy to recalculate with slightly changing numerical values. For example, from FIG. 3B, the Na / K concentration of the second calibration solution is 170/6, 200/8, 22 from the viewpoint of K +.
It can be seen that a ratio such as 0/12 is good.
Although the optimum Na concentration from the viewpoint of K measurement does not match the optimum K concentration from the viewpoint of Na measurement, it is more accurate to determine the concentration with emphasis on K in a wide range.

Conventionally, it has been practiced to eliminate the influence of interference by assuming a selection coefficient. However, since the selection coefficient itself fluctuates with temperature and time and is not constant, an improper calibration is performed. The error also increases with the liquid concentration.
It is the most accurate if you actually calculate and correct the selection coefficient,
For that purpose, three or more kinds of calibration liquids are required, and the measuring device becomes complicated.

[0015]

FIG. 4 schematically shows a general configuration of a dilution type electrolyte analyzer to which the present invention is applied. The calibration liquid and the sample sucked in the sampling section 2 are diluted by the diluting liquid in the diluting section 4, and the electromotive force of each ion is detected by the ion electrode in the electrode section 6. Reference numeral 8 denotes a liquid sending unit for flowing a calibration liquid or a sample into the flow path.

The two types of calibration liquids 1 and 2 may be built in the apparatus, or may be aspirated from the autosampler in the same manner as the sample. In any case, it is desirable to supply to the electrode section 6 through the same dilution system. In addition, it is desirable that the calibration liquid 1 be flowed to the electrode unit 6 and measured every time the sample is measured, similarly to the sample. This is to prevent drift due to temperature fluctuations and the like at the electrodes.

[0017] As calibration liquid ^{1 Na + / K + / Cl} - / HC
The O ₃ ^- concentration is set to 140/4/100/25 (mmol / l). This is, for example, a solution having the following composition (all units are mmol / l). Of _{NaCl 100 KH 2 PO 4 4 NaHCO} 3 25 Na 2 HPO 4 7.5 or _{NaCl 96 KCl 4 NaHCO 3 25 Na} 2 B 4 O 7 9.5 tris- (hydroxymethyl) aminomethane 20 H 3 BO 3 65 Calibration solution 2 The concentration was set as follows.

[0018] (Conventional Example ^{1) Na + / K + /} Cl - = 100
/ 8/60. This is, for example, a solution having the following composition (all units are mmol / l). _{NaCl 32 KCl 8 NaHCO 3 48 tris-} (hydroxymethyl) aminomethane 20 H 3 BO 3 65

[0019] (Conventional Example ^{2) Na + / K + /} Cl - = 160
/ 6/140. This is, for example, a solution having the following composition (all units are mmol / l). NaCl 137 KCl 3 KH ₂ PO ₄ 3 Na ₂ HPO ₄ 11.5

(Example) From FIGS. 3A to 3C, Na ⁺
/ K ⁺ / Cl ⁻ = 200/7/160/26. This is, for example, a solution having the following composition (all units are mmol /
l). _{NaCl 156 KCl 4 NaHCO 3 26 KH} 2 PO 4 3 Na 2 HPO 4 9

FIG. 5 shows the results of calculation by a computer for the calibration solutions of Conventional Examples 1 and 2 and Example.
(A) to (C). (A) is a case where Na ⁺ is measured, and the selection coefficient of the interfering ion K ⁺ is set to the worst value of 0.2,
The K ⁺ concentration was kept constant at 40 mmol / l. (B) shows the case of measuring K ⁺ , where the selection coefficient of the interfering ion Na ⁺ was set to a bad value of 0.005, and the Na ⁺ concentration was kept constant at 100 mmol / l. (C) shows the case of measuring Cl ⁻ , where the worst selection coefficient of interfering ions HCO ₃ ⁻ is set to 0.2 and HC
The O ₃ ^- concentration was kept constant at 0 mmol / l.

It is clear that even if the selectivity of the electrodes is the same, the use of the calibration liquid of the embodiment increases the accuracy in the high concentration region. FIG. 5 shows a case where the selectivity is deteriorated (selection coefficient is made larger). If the selectivity is good, all the lines approach a straight line of y = x as compared with FIG. The embodiment is merely an example, and substantially the same result can be obtained regardless of where the point on the line shown in FIG. 3 is selected.

Next, a change in ion activity based on a change in ionic strength will be described. The ionic strength μ is calculated as follows. Calibration solution 1 0.1515, 0.15
35 Calibration solution 2 Conventional example 1 0.108 Conventional example 2 0.1775 Example 0.216 Assuming that the dilution ratio is 1/25, the activity coefficient f is

(Equation 8) ("Ion-selective electrode" by GJMoody, JBRThomas,
The calculation using Shin Munemori and Kazuo Nishiro, 1977, Kyoritsu Shuppan) is as follows. Activity coefficient f Ratio to calibration solution 1 Calibration solution 1 0.9905 Calibration solution 2 Conventional example 1 0.9209 1.017 Conventional example 2 0.981 0.992 Example 0.8.873 0.980

As described above, in the case of the dilution method, the difference in ionic strength is reduced by dilution. Therefore,
In practice, it does not appear as a measurement error. In some cases, the diluent contains an electrolyte (Na ⁺ , K ⁺ , Cl ⁻ ). In such a case, the equation is different but can be calculated similarly. The calculation formula is as follows.

(Equation 9) CDM: target ion concentration in diluent CDN: interfering ion concentration in diluent D: dilution ratio

Although the concentration of the calibration liquid 1 is set to be near the normal blood value, it is apparent that the concentration of the calibration liquid 2 can be calculated by applying the equation to the equation even when the concentration deviates from the normal value. However,
This is not preferable in terms of measurement accuracy and stability. ^{Furthermore, Na +, K +, Cl} - in not limited, Ca ²⁺ the same ^{concept, Mg 2+, Li +, HCO} 3 - in will be obvious that the same may be also applied.

[0026]

According to the present invention, the first calibration solution of the two types of calibration solutions has a concentration near the normal range of human serum, and the second calibration solution has the worst interfering ion selection coefficient. By setting the concentration to be close to the value and determining the interfering ion concentration, the composition was set so that the measured concentration value did not deviate significantly due to the interfering ions, so using a calibration curve created with two calibration solutions Measurement can be performed in common for blood and urine, and even if the selectivity fluctuates or deterioration occurs, the accuracy does not greatly deviate. Therefore, it is possible to reduce the troublesomeness required for the calibration.

[Brief description of the drawings]

FIG. 1 is a diagram showing conventional calibration and measurement.

FIG. 2 is a diagram showing calibration and measurement in consideration of interfering ions.

FIGS. 3A to 3C are diagrams showing ranges in which the influence of interfering ions is reduced by the present invention for each target ion.

FIG. 4 is a block diagram schematically showing a dilution type electrolyte analyzer to which the present invention is applied.

FIGS. 5A to 5C are diagrams of measured values comparing the example and the conventional example for each target ion.

[Description of Signs] 2 Sampling section 4 Dilution section 6 Electrode section 8 Liquid sending section

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int.Cl. ⁶ , DB name) G01N 27/26 381 G01N 33/96 G01N 33/50

Claims (1)

(57) [Claims] 1. A calibration solution for a clinical electrolyte analyzer by a dilution method using an ion electrode, wherein the first calibration solution of two types of calibration solutions has a concentration near the normal range of human serum. _Assuming that the concentration of one target component in the second calibration solution is C _MC2 , the concentration C _NC2 of an ion serving as an interfering ion with respect to the target ion is given by A calibration solution characterized by being in the vicinity. Here, K _MN is the selection coefficient of interfering ions with respect to the target ion, which is considered to be near the worst value, C _MC1 is the target ion concentration of the first calibration solution, and C _NC1 is the interference ion concentration of the first calibration solution. , _CX is the concentration near the upper limit of the normal value of the target ion at the urine level or near the upper limit of the measurement range, and _CNX is the concentration near the normal value of the interfering ion at the urine level.