Method for detecting oxalate in calcium gluconate and sodium chloride injection

Abstract

The invention discloses a method for detecting oxalate in calcium gluconate and sodium chloride injection, and relates to the technical field of drug analysis and detection. The detection method comprises the following steps: S1, preparing a test solution and a reference solution; s2, adding hydrochloric acid and high-purity zinc into the test solution, standing for 4-6 minutes, adding a phenylhydrazine hydrochloride solution into the test solution, heating until boiling, immediately cooling, and adding hydrochloric acid and a potassium ferricyanide solution to obtain a first mixed solution; adding hydrochloric acid and high-purity zinc into the reference substance solution, standing for 4-6 minutes, adding a phenylhydrazine hydrochloride solution into the reference substance solution, heating until boiling, immediately cooling, and adding a hydrochloric acid solution serving as a potassium ferricyanide solution to obtain a second mixed solution; and judging whether the content of oxalate in the test solution exceeds the standard or not by comparing the color depth of the first mixed solution and the color depth of the second mixed solution. Oxalates in the calcium gluconate and sodium chloride injection can be visually and rapidly detected through colorimetry, specificity and durability are good, and operation is easy and convenient.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical analysis and detection, in particular to a method for detecting oxalate in calcium gluconate and sodium chloride injection. BACKGROUND

[0002] Calcium gluconate is an organic calcium salt that can be used to reduce capillary permeability, increase density, maintain normal excitability of nerves and muscles, strengthen myocardial contractility, and help bone formation. Calcium gluconate and sodium chloride injection is a colorless and clear liquid. It is suitable for the treatment of acute symptomatic hypocalcemia in children and adult patients.

[0003] The current Pharmacopoeia of various countries has the main indicators for the quality control of calcium gluconate and sodium chloride injection, including appearance, pH value, gluconate content, calcium gluconate content, and related substances. Because oxalate has a large polarity, it has no retention on general chromatographic columns; the ultraviolet response is low, and the limit control of the product is strict, so it is difficult to develop a conventional liquid chromatography method to control it. The United States Pharmacopoeia and the calcium gluconate public draft both use anion exchange chromatography separation mode and conductivity detector to improve the response of oxalate. Patent document CN115951000A provides a method for detecting oxalate in calcium gluconate, which uses high-performance liquid chromatography, a conventional C18 chromatographic column, and an external standard method to detect oxalate. However, this method emphasizes "good specificity", but only verifies the impurities in pure calcium gluconate solution; if there are impurities with similar retention times as oxalate in the detection system (such as calcium gluconate degradation products), peak overlap may occur, and further optimization of chromatographic conditions (such as changing the chromatographic column, adjusting the mobile phase pH), readjusting the mobile phase ratio, column temperature or flow rate, and repeated debugging may result in prolonged detection time.

[0004] Therefore, there is a need for a method that can accurately and quickly detect oxalate in calcium gluconate and sodium chloride injection to effectively control the drug quality of calcium gluconate and sodium chloride injection and ensure drug safety. SUMMARY

[0005] The purpose of the present application is to provide a method for detecting oxalate in calcium gluconate and sodium chloride injection to solve the problem of being unable to quickly and accurately control oxalate in calcium gluconate and sodium chloride injection.

[0006] The purpose of the present application can be achieved by the following technical solutions: A method for detecting oxalate in calcium gluconate and sodium chloride injection, comprising the following steps: S1, preparing a test solution and a control solution; S2, add hydrochloric acid A and high-purity zinc to the test solution, stand for 4-6 min, then add phenylhydrazine hydrochloride solution, heat to boiling, immediately cool, add hydrochloric acid B and potassium ferricyanide solution to obtain a first mixed solution; S2, add hydrochloric acid A and high-purity zinc to the test solution, stand for 4-6 min, then add phenylhydrazine hydrochloride solution, heat to boiling, immediately cool, add hydrochloric acid B and potassium ferricyanide solution to obtain a first mixed solution; S3, compare the color of the first mixed solution and the second mixed solution, and determine whether the oxalate content in the test solution exceeds the standard.

[0007] Further, the test solution is a calcium gluconate and sodium chloride injection solution with a specification of 100 mL, containing 2 g of calcium gluconate and 0.675 g of sodium chloride.

[0008] Further, the control solution is an oxalate aqueous solution obtained by dissolving an oxalate standard in water; 1 mL of the oxalate aqueous solution contains 90-110 μg of oxalate, preferably 95-105 μg, and more preferably 100 μg.

[0009] Further, the ratio of the mass of oxalate in the control solution to the mass of the sample of the calcium gluconate and sodium chloride injection solution to be tested is not higher than 0.0002%, and is preferably 0.000004%-0.0002%.

[0010] Further, the oxalate standard includes an alkali metal oxalate, preferably sodium oxalate.

[0011] Further, the mass fraction of hydrochloric acid A and hydrochloric acid B is 37±2%.

[0012] Further, the use amount ratio of the test solution to hydrochloric acid A, high-purity zinc, phenylhydrazine hydrochloride solution, hydrochloric acid B, and potassium ferricyanide solution is 100 mL:8 mL:(1.6-2.4) g:(0.8-1.2) mL:24 mL:(0.95-1.05) mL.

[0013] Further, the use amount ratio of the control solution to hydrochloric acid A, high-purity zinc, phenylhydrazine hydrochloride solution, hydrochloric acid B, and potassium ferricyanide solution is 100 mL:8 mL:(1.6-2.4) g:(0.8-1.2) mL:24 mL:(0.95-1.05) mL.

[0014] Further, the phenylhydrazine hydrochloride solution is composed of phenylhydrazine hydrochloride and water in a use amount ratio of (8-12) mL:1 mL.

[0015] Further, the potassium ferricyanide solution is composed of potassium ferricyanide and water in a use amount ratio of (45-55) mg:1 mL.

[0016] Further, if the color of the first mixed solution is the same as the color of the second mixed solution or the color of the first mixed solution is lighter than the color of the second mixed solution, the content of oxalate in the test product solution is not over standard.

[0017] Compared with the prior art, the present application has the following beneficial effects: 1. The present application provides a method for detecting oxalate in calcium gluconate sodium chloride injection, which comprises the following steps: acidifying the calcium gluconate sodium chloride injection, reducing the oxalate in the calcium gluconate sodium chloride injection into glyoxylic acid by using zinc, reacting the glyoxylic acid with phenylhydrazine hydrochloride to generate phenylhydrazone of glyoxylic acid, adding an oxidizing agent to convert the excess phenylhydrazine into diazonium salt, and then reacting the diazonium salt with the phenylhydrazone of glyoxylic acid to generate an azo compound, and detecting the oxalate by colorimetry. The method is simple and easy to operate, the detection result is accurate and reliable, the specificity is strong, the repeatability is good, and the method can be used for quality control of calcium gluconate sodium chloride injection.

[0018] 2. The detection method provided by the present application does not need to rely on large and precise instruments such as traditional high-performance liquid chromatography detection method and mass spectrometry, and only needs to complete the steps of adding sample, reaction and colorimetry, so that the skill requirement of the operator is low; meanwhile, the reagents used in the experimental process, i.e., hydrochloric acid, high-purity zinc, phenylhydrazine hydrochloride and potassium ferricyanide, are all conventional chemical reagents, which are easy to obtain and have no strict storage conditions, and no special consumables are needed; the key step of the reaction consumes time for a short period, and the whole detection process can be quickly completed in a short time, compared with the instrument analysis method which needs complex sample pretreatment, gradient elution or mass spectrometry scanning, the content of oxalate in the test product can be fed back more quickly, so that the method is suitable for "real-time monitoring" of the production line or rapid batch sampling inspection. The color of the reaction solution of the test product and the control product is directly compared by "color depth colorimetry", so that whether the content of oxalate exceeds the threshold value set by the control product can be quickly and accurately judged, and the result is intuitive and easy to understand. DETAILED DESCRIPTION

[0019] The specific embodiments of the present application are described in detail below, but it should be understood that the protection scope of the present application is not limited by the specific embodiments.

[0020] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "an" and "the" used in the embodiments of the present application and the appended claims are also intended to include the plural forms, unless the context clearly indicates otherwise.

[0021] It should be understood that in various embodiments of the present application, the magnitude of the serial number of each process does not mean the order of execution, and part or all of the steps can be executed in parallel or in sequence, and the execution order of each process should be determined according to its function and inherent logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0022] The weight of the related components mentioned in the embodiment specification of the present application can not only refer to the specific content of each component, but also represent the proportional relationship between the weights of each component. Therefore, as long as the content of the related components in the embodiment specification of the present application is enlarged or reduced in proportion, it is within the scope disclosed in the embodiment specification of the present application. Specifically, the mass mentioned in the embodiment specification of the present application can be μg, mg, g, kg, and other mass units commonly known in the chemical field.

[0023] Unless otherwise defined, all professional terms used herein have the same meaning as generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present application.

[0024] Unless otherwise specified, the various raw materials, reagents, instruments and equipment used in the present application can be purchased from the market or can be prepared by existing methods.

[0025] The embodiment of the present application provides a detection method for oxalate in calcium gluconate and sodium chloride injection, specifically including the following steps: S1, preparing a test solution and a control solution; S2, adding hydrochloric acid A and high-purity zinc to the test solution, standing for 4-6 min, then adding a phenylhydrazine hydrochloride solution, heating to boiling immediately after cooling, adding hydrochloric acid B and potassium ferricyanide solution to obtain a first mixed solution; S2, adding hydrochloric acid A and high-purity zinc to the test solution, standing for 4-6 min, then adding a phenylhydrazine hydrochloride solution, heating to boiling immediately after cooling, adding hydrochloric acid B and potassium ferricyanide solution to obtain a first mixed solution; S3, comparing the color of the first mixed solution and the second mixed solution, and determining whether the content of oxalate in the test solution is excessive.

[0026] In an acidic environment, high-purity zinc acts as a reducing agent to reduce oxalate (C2O4 2-) is reduced to glyoxylate (CHO-COOH). Oxalate, which is difficult to directly develop color, is converted to glyoxylate, which can be subsequently reacted with phenylhydrazine hydrochloride, to prepare for color development; standing for 4-6 min is to ensure that the reduction reaction is fully carried out, so as to avoid deviation of the results due to incomplete reaction. Condensation reaction occurs between glyoxylate and phenylhydrazine hydrochloride to generate hydrazone compounds (an intermediate with a specific structure). Boiling can accelerate the condensation reaction to make it quickly complete; immediate cooling is to terminate the reaction to prevent the generated intermediate from being decomposed or from undergoing side reactions due to continuous heating. Glyoxylate is converted to the hydrazone intermediate, which is more stable in properties and can be further reacted to develop color, to complete the key conversion step before color development. Potassium ferricyanide is used as an oxidizing agent to oxidize the hydrazone compound generated in the previous step to a colored product (usually red or orange-red). The system produces obvious color through the oxidation reaction, and the color depth is positively correlated with the content of the initial oxalate - the higher the content of oxalate, the more glyoxylate is generated, and the more colored product is obtained through oxidation, and the deeper the color. Since the reaction conditions of the test sample and the control sample are completely consistent, the color depth of the mixture liquid is only determined by the initial oxalate content. The oxalate content of the control sample is the critical value of "not exceeding the standard", and its color is the critical color.

[0027] In a specific embodiment, the test sample solution is a calcium gluconate and sodium chloride injection solution with a specification of 100 mL of calcium gluconate 2 g and sodium chloride 0.675 g. A standard specification of calcium gluconate and sodium chloride injection solution sample is taken to ensure the stability of the oxalate detection results for different batches of standard specification of calcium gluconate and sodium chloride injection solution.

[0028] In a specific embodiment, the control sample solution is an oxalate aqueous solution obtained by dissolving an oxalate standard in water; 90-110 μg of oxalate is contained in every 1 mL of the oxalate aqueous solution; preferably 95-105 μg; more preferably 100 μg. In this concentration range, the detection method can sensitively respond to the slight change in the oxalate content of the test sample solution, while ensuring the accuracy of the detection results at different concentration levels, thereby improving the sensitivity and accuracy of the detection.

[0029] In a specific embodiment, the ratio of the mass of oxalate in the control sample solution to the mass of the sample of the calcium gluconate and sodium chloride injection solution to be detected is not higher than 0.0002%, for example 0.000004%, 0.00004%, 0.00008%, 0.0002% or any value between them, preferably 0.000004%-0.0002%.

[0030] The "oxalate concentration limit" of the control solution refers to the ratio of the mass of oxalate in the control solution to the mass of the sample of the calcium gluconate and sodium chloride injection to be tested; for example, "the control solution with an oxalate concentration limit of 0.0002%" means that the ratio of the mass of oxalate in the control solution to the mass of the sample of the calcium gluconate and sodium chloride injection to be tested is 0.0002%. When the mass ratio is within this reasonable range, the systematic error introduced by the improper ratio can be minimized.

[0031] In a specific embodiment, the oxalate standard includes an alkali metal oxalate, preferably sodium oxalate.

[0032] The alkali metal oxalate standard is prepared with a known concentration, specifically containing 90-110 μg of oxalate per 1 mL (most preferably 100 μg), and the ratio of the mass of oxalate to the mass of the oxalate to be tested in the sample is controlled within 0.0002%, which is the critical standard for determining "whether it exceeds the limit"; among them, the detection effect of sodium oxalate is the most stable.

[0033] In a specific embodiment, the mass fraction of the hydrochloric acid A and the hydrochloric acid B is 37±2%. The hydrochloric acid A is used to provide an acidic environment, and the hydrochloric acid B is used to maintain the acidity of the system. Strictly controlling the mass fraction of the hydrochloric acid A and the hydrochloric acid B can effectively maintain the stability of the reaction system, ensure that the detection result is not disturbed by the fluctuation of the reaction system, and improve the accuracy and repeatability of the detection.

[0034] In a specific embodiment, the use amount ratio of the sample solution to the hydrochloric acid A, high-purity zinc, hydrochloric acid phenylhydrazine solution, hydrochloric acid B, potassium ferricyanide solution is 100 mL:8 mL:(1.6-2.4) g:(0.8-1.2) mL:24 mL:(0.95-1.05) mL. Preferably, the use amount ratio of the sample solution to the hydrochloric acid A, high-purity zinc, hydrochloric acid phenylhydrazine solution, hydrochloric acid B, potassium ferricyanide solution is 100 mL:8 mL:2.5 g:(0.98-1.02) mL:24 mL:(0.98-1.02) mL.

[0035] In a specific embodiment, the use amount ratio of the control solution to the hydrochloric acid A, high-purity zinc, hydrochloric acid phenylhydrazine solution, hydrochloric acid B, potassium ferricyanide solution is 100 mL:8 mL:(1.6-2.4) g:(0.8-1.2) mL:24 mL:(0.95-1.05) mL. Preferably, the use amount ratio of the control solution to the hydrochloric acid A, high-purity zinc, hydrochloric acid phenylhydrazine solution, hydrochloric acid B, potassium ferricyanide solution is 100 mL:8 mL:2.5 g:(0.98-1.02) mL:24 mL:(0.98-1.02) mL.

[0036] The above-mentioned test sample solution and control sample solution and hydrochloric acid A, high-purity zinc, hydrochloric acid phenylhydrazine solution, hydrochloric acid B, potassium ferricyanide solution are the same in the dosage ratio, which is easy to control the variable; within the ratio range, the chemical reactions between the substances can occur fully. If the amount of the test sample solution is too much or too little, the balance and suitability of the reaction will be broken.

[0037] In a specific embodiment, the hydrochloric acid phenylhydrazine solution is composed of hydrochloric acid phenylhydrazine and water in a dosage ratio of (8-12) mL: 1 mL. At this concentration, the reaction between hydrochloric acid phenylhydrazine and glyoxylic acid can proceed fully and efficiently, and a sufficient amount of phenylhydrazone of glyoxylic acid is generated to provide sufficient material basis for the subsequent reaction with diazonium salt to generate pink azo compounds. Preferably, the hydrochloric acid phenylhydrazine solution is composed of hydrochloric acid phenylhydrazine and water in a dosage ratio of (9-11) mL: 1 mL. When the hydrochloric acid phenylhydrazine and water are in this ratio, the color development reaction is sensitive and stable, the pink azo compounds generated are bright in color, easy to observe and compare, and the content of oxalate can be accurately judged by colorimetry.

[0038] In a specific embodiment, the potassium ferricyanide solution is composed of potassium ferricyanide and water in a dosage ratio of (45-55) mg: 1 mL. This concentration can ensure that potassium ferricyanide has a suitable oxidation capacity and concentration in the solution. The suitable oxidation capacity enables it to accurately convert excess phenylhydrazine into diazonium salt, and the suitable concentration ensures that the reaction can proceed fully to generate a significant color change. Preferably, the potassium ferricyanide solution is composed of potassium ferricyanide and water in a dosage ratio of (48-52) mg: 1 mL. When the potassium ferricyanide solution is in this concentration, it can work synergistically with other reagents to make the pink azo compounds generated by the reaction more stable and obvious in color.

[0039] In a specific embodiment, if the color of the first mixed solution is the same as or lighter than that of the second mixed solution, the content of oxalate in the test sample solution is not over-standard. The oxalate in calcium gluconate and sodium chloride injection is directly and quickly detected by colorimetry, which is not only specific and durable, but also simple to operate, saving detection time and cost. It can be applied to the quality control of calcium gluconate and sodium chloride injection, is conducive to the promotion and use in production, and has great significance for the clinical safety and effectiveness of calcium gluconate and sodium chloride injection.

[0040] The following will be further illustrated with specific embodiments.

[0041] Example 1

[0042] A method for detecting oxalate in calcium gluconate and sodium chloride injection, comprising the following steps: S1, preparing a test sample solution and a control sample solution; 1) Test solution: Take 25 mL of calcium gluconate and sodium chloride injection; 2) Control solution: Take 0.1523 g of sodium oxalate, add water to dissolve and dilute to 1000 mL in a volumetric flask, and dilute to 1.523 mg of sodium oxalate per 1 mL. Precisely take 4 mL of sodium oxalate solution, dilute with water to 100 mL as the control solution. The oxalate concentration limit of this solution is 0.0002%. S2, add 2 mL of hydrochloric acid A and 0.5 g of high-purity zinc to 25 mL of the test solution, stand for 5 min, then add 0.25 mL of 10 mg / mL phenylhydrazine hydrochloride solution (take 100 mg of phenylhydrazine hydrochloride, dissolve and dilute with 10 mL of water, and prepare fresh before use), heat to boiling immediately after cooling, add 6 mL of hydrochloric acid B and 0.25 mL of 50 mg / mL potassium ferricyanide solution (take 500 mg of potassium ferricyanide, dissolve and dilute with 10 mL of water, and prepare fresh before use), mix well to get the first mixed solution; Add 2 mL of hydrochloric acid A and 0.5 g of high-purity zinc to 25 mL of the control solution, stand for 5 min, then add 0.25 mL of 10 mg / mL phenylhydrazine hydrochloride solution, heat to boiling immediately after cooling, add 6 mL of hydrochloric acid B and 0.25 mL of 50 mg / mL potassium ferricyanide solution, mix well to get the second mixed solution; S3, compare the color of the first mixed solution and the second mixed solution, and determine whether the content of oxalate in the test solution exceeds the limit.

[0043] According to the above method, the oxalate in 9 batches of calcium gluconate and sodium chloride injection was detected by using the control solution with oxalate concentration limit of 0.00004% and 0.00008%, respectively. The results are shown in Table 1. The preparation method of the control solution with oxalate concentration limit of 0.00004% and 0.00008% is as follows: Preparation of control solution with oxalate concentration limit of 0.00004%: precisely take 2 mL of the above prepared control solution with oxalate concentration limit of 0.0002%, add water to 10 mL in a volumetric flask, shake well to get the control solution with oxalate concentration limit of 0.00004%.

[0044] Preparation of control solution with oxalate concentration limit of 0.00008%: precisely take 4 mL of the above prepared control solution with oxalate concentration limit of 0.0002%, add water to 10 mL in a volumetric flask, shake well to get the control solution with oxalate concentration limit of 0.00008%.

[0045] Table 1 Detection results of oxalate in calcium gluconate and sodium chloride injection samples

[0046] Example 2

[0047] Specificity test: Sodium oxalate solution: precisely weigh sodium oxalate dried at 105℃ to constant weight 0.1523g, put into 1000mL volumetric flask, dissolve and dilute to the mark with water, shake well, containing 0.1mg of C2O4 per 1mL 2- .

[0048] Blank interference experiment: take water 25mL into a colorimetric tube, add hydrochloric acid 2mL, about 0.5g of high-purity zinc, stand for 5min, add 10mg / mL hydrochloric acid phenylhydrazine solution (freshly prepared) 0.25mL, heat to boiling immediately after cooling, add hydrochloric acid 6mL, 50mg / mL potassium ferricyanide solution (freshly prepared) 0.25mL, shake well.

[0049] Test solution: take calcium gluconate sodium chloride injection 25mL into a colorimetric tube, add hydrochloric acid 2mL, about 0.5g of high-purity zinc, stand for 5min, add 10mg / mL hydrochloric acid phenylhydrazine solution (freshly prepared) 0.25mL, heat to boiling immediately after cooling, add hydrochloric acid 6mL, 50mg / mL potassium ferricyanide solution (freshly prepared) 0.25mL, shake well.

[0050] Control solution: take sodium oxalate solution 0.5mL, add water 25mL into a colorimetric tube, add hydrochloric acid 2mL, about 0.5g of high-purity zinc, stand for 5min, add 10mg / mL hydrochloric acid phenylhydrazine solution (freshly prepared) 0.25mL, heat to boiling immediately after cooling, add hydrochloric acid 6mL, 50mg / mL potassium ferricyanide solution (freshly prepared) 0.25mL, shake well.

[0051] Specificity solution: take calcium gluconate sodium chloride injection 25mL into a colorimetric tube, add sodium oxalate solution 0.5mL, add hydrochloric acid 2mL, about 0.5g of high-purity zinc, stand for 5min, add 10mg / mL hydrochloric acid phenylhydrazine solution (freshly prepared) 0.25mL, heat to boiling immediately after cooling, add hydrochloric acid 6mL, 50mg / mL potassium ferricyanide solution (freshly prepared) 0.25mL, shake well.

[0052] The colorimetric test shows that: the blank solvent has no interference; the color of the specificity solution is close to the control solution and deeper than the test solution; the specificity solution is clear and distinguishable, and the method has good specificity.

[0053] Example 3

[0054] Detection limit: According to the detection method of Example 2, prepare blank solution and series of limit control solution, to the lowest limit that can be reliably detected, the detection limit results are shown in Table 2.

[0055] Table 2 detection limit results

[0056] From Table 2, the color of the control solution is proportional to the concentration. The control solution containing 0.001 mg of oxalate (0.000004% limit control solution) is visually distinguishable compared to the blank solution, which is the lowest amount (minimum limit) that can be visually clearly distinguished, i.e. the detection limit is 0.001 mg (equivalent to a limit of 0.000004%), indicating that the detection limit of the method of the present application can be as low as 0.000004%.

[0057] Examples 4-5

[0058] According to the detection method in Example 1, the standing time was changed to 4 min and 6 min, and the color change of the solution was observed to investigate the robustness of the method. The results are shown in Table 3.

[0059] Table 3

[0060] As can be seen from Table 3, the standing time is within 4-6 min, the color of the robustness solution is consistent and clearly distinguishable, and the detection results are not affected.

[0061] Examples 6-7

[0062] According to the detection method in Example 1, the amount of phenylhydrazine hydrochloride solution added was changed to 0.20 mL and 0.30 mL, and the color change of the solution was observed to investigate the effect of phenylhydrazine hydrochloride solution on the detection. The results are shown in Table 4.

[0063] Comparative Examples 1-2

[0064] According to the detection method in Example 1, the amount of phenylhydrazine hydrochloride solution added was changed to 0.15 mL and 0.35 mL, and the color change of the solution was observed to investigate the effect of phenylhydrazine hydrochloride solution on the detection. The results are shown in Table 4.

[0065] Table 4

[0066] As can be seen from Table 4, reducing or increasing the amount of phenylhydrazine hydrochloride will affect the accuracy and sensitivity of the detection. Within the range of considering weighing and configuration errors, the detection effect of 100: (0.8-1.2) in the present application is the best.

[0067] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting; it is not intended to exclude myriad other embodiments of the present application that other inventors can develop based on the description herein. It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a component" or "the component" can include a plurality of such components unless the context clearly dictates otherwise.

[0068] The foregoing disclosure specifically encompasses all changes and modifications of the specific embodiments described herein falling within the scope of the invention. It is to be understood that the application is not limited to the specific embodiments described herein, which are presented for illustrative purposes only.

Claims

1. A method for detecting oxalate in calcium gluconate sodium chloride injection, characterized in that, Includes the following steps: S1. Prepare the test solution and the reference solution; S2. Add hydrochloric acid A and zinc to the test solution, let stand for 4-6 minutes, then add hydrochloric acid phenylhydrazine solution, heat to boiling and cool immediately, add hydrochloric acid B and potassium ferricyanide solution to obtain the first mixture. Add hydrochloric acid A and zinc to the reference solution, let stand for 4-6 minutes, then add hydrochloric acid phenylhydrazine solution, heat to boiling and cool immediately, add hydrochloric acid B and potassium ferricyanide solution to obtain the second mixture; S3. Compare the color of the first and second mixtures to determine whether the oxalate content in the test solution exceeds the standard.

2. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 1, characterized in that, The test solution is a calcium gluconate and sodium chloride injection solution with a specification of 100mL containing 2g of calcium gluconate and 0.675g of sodium chloride.

3. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 1, characterized in that, The reference solution is an aqueous solution of oxalate obtained by dissolving oxalate standard in water; each 1 mL of the aqueous solution of oxalate contains 90-110 μg of oxalate.

4. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 3, characterized in that, The oxalate standard is an alkali metal oxalate.

5. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 4, characterized in that, The oxalate standard is sodium oxalate.

6. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 1, characterized in that, The ratio of the volume of the test sample solution to hydrochloric acid A, high-purity zinc, phenylhydrazine hydrochloride solution, hydrochloric acid B, and potassium ferricyanide solution is 100 mL: 8 mL: (1.6-2.4) g: (0.8-1.2) mL: 24 mL: (0.95-1.05) mL.

7. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 1, characterized in that, The ratio of the reference solution to hydrochloric acid A, high-purity zinc, phenylhydrazine hydrochloride solution, hydrochloric acid B, and potassium ferricyanide solution is 100 mL: 8 mL: (1.6-2.4) g: (0.8-1.2) mL: 24 mL: (0.95-1.05) mL.

8. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 1, characterized in that, The phenylhydrazine hydrochloride solution is composed of phenylhydrazine hydrochloride and water in a volume ratio of (8-12) mL: 1 mL.

9. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 1, characterized in that, The potassium ferricyanide solution is composed of potassium ferricyanide and water in a ratio of (45-55) mg: 1 mL.

10. The method for detecting oxalate in calcium gluconate sodium chloride injection according to claim 1, characterized in that, If the color of the first mixture is the same as the color of the second mixture, or if the color of the first mixture is lighter than the color of the second mixture, then the oxalate content in the test solution does not exceed the standard.

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