Method for measuring content of cyanide in sodium nitroprusside by potentiometric titration
Through the potential titration method combined with EDTA and cyanide ion selective electrodes, the complexity and false negative problems of cyanide content detection in sodium nitroprusside were solved, and high-sensitivity and low-cost trace cyanide detection was achieved, which was especially suitable for drug detection.
Patent Information
- Application Number
- CN202510305880.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-14
- Publication Date
- 2025-07-11
AI Technical Summary
The prior art has complex operation, low sensitivity, high risk, high cost and prone to false negative results when determining the cyanide content in sodium nitroprusside. In particular, there is a lack of effective low-concentration cyanide detection method in drug testing.
The content of cyanide in sodium nitroprusside was measured by potentiometric titration by adding EDTA solution under alkaline conditions to complex the metal ions in the solution, and using a silver/silver chloride electrode as the reference electrode.
It realizes trace cyanide detection with high sensitivity, low cost and good safety, solves the problems of complex operation, high risk and false negative in the prior art, and is suitable for the accurate determination of trace cyanide in drugs.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for determining the content of cyanide in sodium nitroprusside by potentiometric titration. Background Art
[0002] Sodium nitroprusside injection is one of the therapeutic drugs for hypertensive emergencies and acute heart failure. Its main component is sodium nitroprusside, with the molecular formula of Na2[Fe(CN)5NO]×2H2O, and the structural formula is as follows.
[0003]
[0004] The aqueous solution of sodium nitroprusside is prone to degradation under high temperature and light conditions, and one of the degradation products is cyanide. Cyanide can cause serious toxic reactions and affect the safety of the product. Therefore, a suitable method is required to detect cyanide in sodium nitroprusside raw materials and injections.
[0005] Currently, for the detection methods of cyanide, mainly gas chromatography, spectrophotometry, silver nitrate titration, ion chromatography (with amperometric detector) and ion selective electrode method are used, but they are basically applied in environmental pollution and control and food safety, such as the determination of cyanide in water and wastewater, and there is no application in drug detection. Among them, both gas chromatography and spectrophotometry need to react cyanide with chloramine T first to generate highly toxic cyanogen chloride, and then use the low boiling point property and electronegativity of cyanogen chloride to achieve gas phase separation and detect with an electron capture detector. It is also possible to react cyanogen chloride with isonicotinic acid and hydrolyze to form a chromogenic compound, and measure its absorbance to achieve the detection of cyanide. Both of these methods are relatively complex in operation and have safety risks. Silver nitrate titration is only used when the cyanide concentration in the sample is relatively high (greater than 1mg / mL), with insufficient sensitivity and is not suitable for the determination of low concentration of cyanide content. The detection of ion chromatography requires a special detector (amperometric detector), and the instrument is expensive, with high detection costs.
[0006] The ion selective electrode method is used to detect cyanide. The principle of this method is that under alkaline conditions, the potential difference between two electrodes in the solution to be measured is measured by using a cyanide ion selective electrode and a reference electrode. According to the measured potential difference being proportional to the logarithm of the cyanide ion concentration in the solution, the concentration of cyanide ions in the solution is thus determined. At present, the determination of cyanide by using a cyanide ion selective electrode is mainly used for the determination of cyanide in environmental water and wastewater. However, most of them do not consider the problem of using EDTA to remove the interference of metal ions. For example, in the "Analysis of the Determination Method and Influencing Factors of Cyanide in the Effluent of Sewage Treatment Plants" (Xi'an University of Science and Technology, 2014), the relevant research content on the influencing factors of determining cyanide concentration by using the selective electrode method is disclosed, and the method of using EDTA to remove the interference of metal ions is not mentioned in the method of excluding anti-interference factors. This literature does not consider the influence of metal ions in the solution on the determination of cyanide, which may cause the detection result to be false negative.
[0007] To solve the problems of complex operation, low sensitivity, high danger, false negative and high detection cost existing in the above-mentioned existing methods, the present invention provides a method for determining the content of cyanide in sodium nitroprusside by potentiometric titration. This method not only has high sensitivity and good safety, but also has the advantages of simple operation, rapid detection and low detection cost, and is particularly suitable for the determination of trace cyanide content in drugs. The solution in the present invention has higher sensitivity. This situation is considered in the solution of the present invention, and EDTA is added to the solution to complex the metal ions in the solution, effectively improving the recovery rate of the analysis method. Summary of the Invention
[0008] The purpose of the present invention is to provide a method for determining the content of cyanide in sodium nitroprusside by potentiometric titration. This method uses EDTA to exclude the interference of metal ions on the detection, effectively improving the recovery rate of the analysis method.
[0009] To achieve the purpose of the present invention, the following implementation schemes are provided.
[0010] In one implementation scheme, a method for determining the content of cyanide in sodium nitroprusside by potentiometric titration according to the present invention is characterized in that: a cyanide ion selective electrode is used as the indicating electrode, and a silver / silver chloride electrode is used as the reference electrode; sodium ethylenediaminetetraacetate (EDTA) solution is added to the solution to be measured, and the content of cyanide in sodium nitroprusside is measured under alkaline conditions.
[0011] Preferably, in the method of the present invention above, EDTA is added to the solution to be measured, and the concentration of EDTA in the solution to be measured is 1-10 mmol / L, more preferably 2-5 mmol / L.
[0012] Further, in the method of the present invention above, the measurement is carried out under alkaline conditions, that is, an alkaline solution is added to the solution to be measured, and the alkali is sodium hydroxide solution.
[0013] Preferably, in the method of the present invention described above, the addition amount (dosage) of the sodium hydroxide solution is 80 μL to 500 μL of 1 mol / L sodium hydroxide solution added to every 25 mL of the solution to be measured, and more preferably 100 μL to 200 μL of 1 mol / L sodium hydroxide solution added to every 25 mL of the solution.
[0014] Preferably, in the method of the present invention described above, after adding a specified amount of sodium hydroxide solution to the solution to be measured, the stirring time is not less than 6 min before starting the measurement.
[0015] In a specific embodiment, a method for determining the cyanide content in sodium nitroprusside by potentiometric titration according to the present invention is characterized in that: a cyanide ion selective electrode is used as the indicating electrode, and a silver / silver chloride electrode is used as the reference electrode to measure the potential difference generated by cyanide ions in the solution. Disodium ethylenediaminetetraacetate (EDTA) solution is added to the solution to be measured, and the cyanide content in sodium nitroprusside is measured under alkaline conditions, including the following process: 1) Preparation of 0.1 mol / L EDTA solution: Weigh 0.372 g of disodium ethylenediaminetetraacetate dihydrate and dissolve it in 100 mL of water. Preparation of 1 mol / L sodium hydroxide solution: Weigh 4.0 g of sodium hydroxide and dissolve it in 100 mL of water; 2) Preparation of blank solution: Take a 25 ml volumetric flask, add 0.5 - 2.0 mL of 0.1 mol / L EDTA solution, dilute to the mark with purified water, and shake well. The solution contains 2 - 8 mmol / L of EDTA; 3) Preparation of standard curve solution: Weigh an appropriate amount of potassium cyanide, add purified water to make solutions containing 0.1 μg / mL, 0.2 μg / mL, 2.5 μg / mL, 5 μg / mL, and 10 μg / mL of cyanide ions per milliliter, each with a volume of 25 mL. Before each standard curve solution is made up to 25 mL, add 0.5 - 2.0 mL of 0.1 mol / L EDTA solution respectively; 4) Preparation of test solution (under light - proof operation): Weigh an appropriate amount of sodium nitroprusside, place it in a 25 mL volumetric flask, add 0.5 - 2.0 mL of 0.1 mol / L EDTA solution, and make a 25 mL solution containing 4 mg / mL of sodium nitroprusside with purified water; 5) Determination of standard curve solution: Before measuring each standard curve solution, add 80 - 500 μL of 1 mol / L sodium hydroxide solution, shake well, automatically stir with a potentiometric titrator for not less than 6 minutes, and then immediately measure and record the potential difference value; 6) Determination of test solution (under light - proof operation): Before measuring each test solution to be measured, add 80 - 500 μL of 1 mol / L sodium hydroxide solution, shake well, automatically stir with a potentiometric titrator for not less than 6 minutes, and then immediately measure and record the potential difference value; 7) Calculation: Take the logarithm of the concentration of the standard curve solution (in terms of cyanide ions) as the abscissa, and the measured potential difference as the ordinate to establish a standard curve, and record the standard curve equation. Then substitute the measured potential difference of the test solution into the standard curve equation to calculate the concentration of cyanide ions in the test solution.
[0016] Technical effects: In the present invention, a certain amount of EDTA is added to the solution to be tested, so that some metal ions in the solution are complexed with it, avoiding the interference of metal ions on the determination of cyanide ions, and greatly improving the method sensitivity and accuracy. The optimal amount of EDTA added is 1.0 - 1.5 mL of 0.1 mol / L EDTA solution per 25 mL of solution, that is, the solution contains 4 - 6 mmol / L of EDTA.
[0017] Cyanide ions are prone to form hydrocyanic acid in acidic water. In the present invention, an appropriate amount of base is added to the solution so that hydrocyanic acid in the solution to be tested exists as free cyanide ions to improve the method accuracy. Adding too much base will cause the degradation of sodium nitroprusside, and the degradation products will affect the determination of cyanide ions. Therefore, the amount of base added needs to be controlled within a certain range. The optimal amount of sodium hydroxide added is 100 - 200 μL of 1 mol / L sodium hydroxide solution per 25 mL of solution.
[0018] The method of the present invention has high sensitivity, good safety, and has the advantages of simple operation, rapid detection, low detection cost, and good accuracy, and is particularly suitable for the determination of trace cyanide content in drugs. It also well solves the technical problems of the prior art in the determination of cyanide in sodium nitroprusside, such as complex operation, operation danger, poor repeatability, low sensitivity, false negative results, etc. It provides a new solution for the quality control of sodium nitroprusside raw materials and their related preparations. Description of the drawings
[0019] Figure 1 It is a standard curve graph of the cyanide ion solution. Detailed implementation manners
[0020] The following further illustrates the present invention through examples, but the examples do not limit the protection scope of the present invention.
[0021] Main instrument and equipment: Metrohm 809 potentiometric titration analyzer. With automatic stirring function. Use a cyanide ion selective electrode as the indicator electrode and a silver / silver chloride electrode as the reference electrode.
[0022] Reagents and drugs: Disodium ethylenediaminetetraacetate dihydrate (EDTA), sodium hydroxide, sodium nitroprusside, purified water, etc.
[0023] Screening Test of the Method in Example 1 In this test, the appropriate test conditions were screened by adjusting the concentration of EDTA, the addition amount of sodium hydroxide, the stirring time, etc. The specific scheme is shown in Table 1.
[0024]
[0025] The results in Table 1 show that under the measurement conditions of Scheme 4 to Scheme 7, when the addition amount of cyanide ion is 8 ppm, the recovery rates are all greater than 80%, which can be applied to the determination of trace cyanide in sodium nitroprusside. In Scheme 1 and Scheme 8, due to the addition of excessive sodium hydroxide, the color of the solution changed significantly, indicating that sodium nitroprusside had degraded, which affected the determination of cyanide ion. The recovery rates of cyanide ion measured by these two schemes were both low and could not meet the requirements of the determination. In Scheme 2, no sodium hydroxide was added, and the standard curve solution was not linear, so the recovery rate result could not be obtained, and thus it could not meet the requirements of the determination. In Scheme 3, no EDTA was added, and the recovery rate of cyanide ion was low, so it could not meet the requirements of the determination either.
[0026] Example 2 Preparation of Standard Curve The measurement conditions adopted Scheme 6 in Example 1.
[0027] Preparation of standard curve solution: Weigh an appropriate amount of potassium cyanide and add purified water to prepare 25 mL of solutions containing 0.1 μg / mL, 0.2 μg / mL, 2.5 μg / mL, 5 μg / mL, and 10 μg / mL of cyanide ion per milliliter respectively. And before each standard curve solution was made up to 25 mL, 1.0 mL of 0.1 mol / L EDTA solution was added respectively.
[0028] Take each standard curve solution and add 100 μL of 1 mol / L sodium hydroxide solution before measurement, and shake well. After automatically stirring with a potentiometric titrator for no less than 6 minutes, measure immediately and record the potential difference.
[0029] Taking the logarithm of the concentration of the standard curve solution (calculated as cyanide ion) as the abscissa and the measured potential difference as the ordinate, a standard curve was established. The standard curve equation obtained was: Y = -60.701X - 74.7924, and the correlation coefficient r was 0.9996. Where Y is the potential difference and X is the logarithm of the cyanide ion concentration in the solution, see Figure 1 .
[0030] Example 3 Determination of the Quantitation Limit and Detection Limit of the Method The blank solution was measured under the conditions of Scheme 6 in Example 1. It was continuously measured no less than 6 times, and the standard deviation of the measured values was calculated. Divide the 3.3-fold standard deviation value by the slope of the standard curve equation, which is the detection limit concentration of the method; divide the 10-fold standard deviation value by the slope of the standard curve equation, which is the quantification limit concentration of the method. Through measurement, the detection limit concentration of the method was 0.0049 μg / mL, and the quantification limit concentration was 0.015 μg / mL. It shows that the method of the present invention has high sensitivity.
[0031] Example 4 Recovery Test The measurement conditions were the same as those in Scheme 6 of Example 1.
[0032] Preparation of sodium nitroprusside solution (operate in the dark): Weigh a certain amount of sodium nitroprusside and dilute it with water to a solution containing about 25 mg / mL of sodium nitroprusside for standby.
[0033] Preparation of test solution (operate in the dark): Precision measure 4 mL of the above sodium nitroprusside solution, place it in a 25 mL volumetric flask, add 1.0 mL of 0.1 mol / L EDTA solution, dilute to the mark with purified water, and shake well.
[0034] Preparation of spiked test solution: Precision measure 4 mL of the above sodium nitroprusside solution, place it in a 25 mL volumetric flask, first add 1.0 mL of 0.1 mol / L EDTA solution, then add a certain amount of potassium cyanide solution with a known concentration, dilute to the mark with purified water, and shake well.
[0035] Add 100 μL of 1 mol / L sodium hydroxide solution to each of the above test solutions and spiked test solutions to be measured before measurement, and shake well. After automatically stirring with a potentiometric titrator for no less than 6 minutes, immediately measure and record the potential difference.
[0036] Calculation: Substitute the measured potential differences of each test solution and spiked test solution into the standard curve equation to calculate the concentration of cyanide ions in each test solution and spiked test solution.
[0037] The results of the recovery rate are shown in Table 2. The measured amount is the concentration of cyanide ions in the spiked test sample minus the background amount (i.e., the concentration of cyanide ions in the test solution).
[0038]
[0039] The results in Table 2 show that the average recovery rate of the method is 93.6%, and the RSD of the recovery rates of 9 solutions at 3 concentrations is 5.8%. It shows that the method has good accuracy.
Claims
1. A method for determining the cyanide content in sodium nitroprusside by potentiometric titration, characterized in that : Comprising using a cyanide ion selective electrode as the indicating electrode and a silver / silver chloride electrode as the reference electrode; adding a disodium ethylenediaminetetraacetate (EDTA) solution to the solution to be measured, and determining the content of cyanide in sodium nitroprusside under alkaline conditions.
2. The method according to claim 1, wherein in the solution to be measured, the concentration of EDTA is 1 to 10 mmol / L.
3. The method according to claim 2, wherein the concentration of EDTA is 2 to 6 mmol / L.
4. The method according to claim 3, wherein the concentration of EDTA is 4 mmol / L.
5. The method according to claim 1, wherein the base is a sodium hydroxide solution.
6. The method according to claim 5, wherein the dosage of the sodium hydroxide solution is 80 μL to 500 μL of 1 mol / L sodium hydroxide solution added to every 25 mL of the solution to be measured.
7. The method according to claim 6, wherein the dosage of the sodium hydroxide solution is 100 μL to 200 μL of 1 mol / L sodium hydroxide solution added to every 25 mL of the solution.
8. The method according to claim 7, wherein the dosage of the sodium hydroxide solution is 100 μL of 1 mol / L sodium hydroxide solution added to every 25 mL of the solution.
9. The method according to claim 5 or 6, wherein after adding the specified amount of sodium hydroxide solution, the stirring time is not less than 6 min.