Method for detecting calcium salt in ferrous gluconate
By mixing sodium sulfide with ferrous gluconate solution to remove ferrous ions, and then adding water and ammonium oxalate solution to observe the clarification situation in the colorimetric tube, the problem of the inability to accurately detect calcium salts in ferrous gluconate in the existing methods is solved, and a simple and efficient detection effect is achieved.
Patent Information
- Application Number
- CN202311705840.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-13
- Publication Date
- 2025-06-13
AI Technical Summary
The existing methods for checking calcium salts in ferrous gluconate cannot be accurately detected because ferrous ions react with oxalate ions to produce precipitates, resulting in the solution not being clarified and the existence of calcium salts cannot be distinguished.
By mixing sodium sulfide with ferrous gluconate solution, the ferrous ion precipitation was removed, the supernatant was taken as the test solution, and then water and saturated ammonium oxalate solution were added to the colorimetric tube respectively to observe whether it was the same clarity to judge the presence of calcium salt.
This method can effectively remove ferrous ions, avoid precipitation caused by ammonium oxalate test solution, accurately detect the existence of calcium salts in ferrous gluconate, and is easy to observe. It is suitable for the detection of calcium salts in ferrous gluconate.
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Abstract
Description
Technical Field
[0001] The present invention relates to the field of chemical drug analysis, and particularly to a method for inspecting calcium salts in ferrous gluconate. Background Art
[0002] The method for determining calcium salts in ferrous gluconate in the 2020 Edition of Chinese Pharmacopoeia is as follows: "Take 2.0 g of this product, dissolve it in 100 ml of water, and divide it into two equal parts: add 5 ml of ammonium oxalate test solution to one part, and add 5 ml of water to the other part. Let it stand for 5 minutes, and the two liquids should be equally clear." However, since ferrous ions will react with oxalate ions to form a precipitate, the solution will surely become turbid after adding ammonium oxalate test solution, and this method cannot accurately inspect the calcium salts in ferrous gluconate. It is found that the solubility product constant of ferrous oxalate is 2.1×10 -7 (at 25 °C). According to the detection method, the concentration of ferrous ions can be calculated as 0.0395 mol / L, and the concentration of oxalate is 0.0134 mol / L. The product of the two is 5.30×10 -4 , which is much greater than its solubility product constant of 2.1×10 -7 . The calculation results also show that a precipitate will be formed. Therefore, there is an urgent need to develop a method for inspecting calcium salts in ferrous gluconate to meet the quality control requirements of ferrous gluconate. Summary of the Invention
[0003] The purpose of the present invention is to provide a method for inspecting calcium salts in ferrous gluconate, which can effectively solve the problems in the background art.
[0004] To achieve the above purpose, the technical solution adopted by the present invention is as follows:
[0005] A method for inspecting calcium salts in ferrous gluconate, characterized by comprising the following steps:
[0006] (1) Removal of ferrous salts: Take sodium sulfide and ferrous gluconate and dissolve them in water. Mix the two liquids, shake well, let it stand for sufficient reaction, remove the precipitate, and take the supernatant as the test solution.
[0007] (2) Inspection of calcium salts: Take two portions of the test solution and place them in colorimetric tubes respectively. Add water to one portion and saturated ammonium oxalate solution to the other portion. Let it stand. If the two liquids are equally clear, it indicates that the calcium salts in ferrous gluconate are within a certain limit.
[0008] Preferably, the specific method of step (1) is to take 3.0 g of sodium sulfide and dissolve it in 15.0 ml of water, take 0.50 g of ferrous gluconate and dissolve it in 10.0 ml of water. Mix the two liquids, shake well, let it stand for sufficient reaction, remove the precipitate, and take the supernatant as the test solution.
[0009] Preferably, in step (1), the method for removing the precipitate is to filter first with filter paper and a filter membrane, and then perform centrifugation; preferably, the filter membrane is a 0.22 μm filter membrane; preferably, the centrifugation rate is 4000 rpm and the centrifugation time is 10 min.
[0010] Preferably, the specific inspection method for step (2) is as follows: Take two 5 ml test solution samples and place them in colorimetric tubes respectively. Add 2 ml of water to one tube and 2 ml of saturated ammonium oxalate solution to the other tube, and let it stand for 5 minutes. If the two solutions are equally clear, it indicates that the calcium salt in ferrous gluconate meets the requirements (within 0.02%).
[0011] Technical effects of the present invention:
[0012] After the ferrous ions are precipitated with sulfide ions in this analytical method, the ferrous ions are removed by filtration followed by centrifugation. Then, the calcium salt is precipitated by adding ammonium oxalate solution. The calcium ions in the sample can be successfully detected. Moreover, the operation method is simple, the phenomenon is easy to observe, and the method has good specificity and repeatability, and is applicable to the detection of calcium salt in ferrous gluconate. Detailed implementation manners
[0013] The following combines with the detailed implementation manners to further elaborate on the technical solutions of the present invention in detail, but does not constitute any limitation to the present invention.
[0014] 1. Route screening
[0015] 1.1 Using masking agents to mask ferrous ions to avoid interference
[0016] Using citric acid, tartaric acid, triethanolamine, copper reagent, etc. to mask ferrous ions, the results show that the colors after complexing with ferrous ions are all relatively deep, and the suspensions formed cannot be filtered completely, affecting the judgment of precipitation, as shown in Table 1.
[0017] Table 1 Attempts to mask ferrous ions
[0018]
[0019] 1.2 Making ferrous ions form precipitates and filtering them out
[0020] The method requires that ferrous ions can form precipitates and be removed without forming precipitates with a small amount of calcium ions. Through research and analysis of anions such as S 2- 、PO 4 3- 、CO 3 2- 、OH - 、MoO 4 2- 、C 2 0 4 2- etc., as shown in Table 2 in detail. It is considered that S 2-is a relatively feasible anion.
[0021] Table 2 Comparative analysis of the ability of various anions to remove ferrous ions
[0022]
[0023]
[0024] By using S 2- ions to remove ferrous ions, a detection method for calcium salts in ferrous gluconate was established, and a series of investigations were carried out. The detailed process can be seen in "2. Method investigation" and "3. Methodology verification".
[0025] 2. Method investigation
[0026] 2.1 Calcium detection limit
[0027] The limit of calcium salts in the determination method of calcium salts in ferrous gluconate in the 2020 edition of the Chinese Pharmacopoeia is not clear. A series of calcium ion solutions with different concentrations were prepared, ammonium oxalate was added, and the concentration at which precipitation occurred was investigated. Then, based on the sampling amount of ferrous gluconate in the determination method, the calcium content in ferrous gluconate when precipitation would occur was calculated. The results are as follows:
[0028]
[0029] It can be seen from the above table that the detection limit of calcium salts is 3.568 - 4.460 μg / ml. According to the sampling amount of ferrous gluconate, the corresponding calcium content in ferrous gluconate can be calculated to be 0.018% - 0.022%. Continuing the investigation, a 50 ml solution with a calcium ion concentration of 4.0 μg / ml was prepared, 5 ml of ammonium oxalate solution was added, and no precipitation occurred at 5 minutes, indicating that the sensitivity of this method for calcium detection is not higher than 4.0 μg / ml (equivalent to 0.02% calcium in ferrous gluconate).
[0030] 2.2 Dosage of sodium sulfide
[0031] It was found in the experiment that an excess of sodium sulfide is required to ensure the precipitation and filtration of ferrous ions.
[0032]
[0033] In summary, the dosage of sodium sulfide was determined to be 3.0 g.
[0034] 2.3 Method for removing ferrous sulfide precipitate
[0035]
[0036] In summary, filtration followed by centrifugation was selected as the method for removing ferrous sulfide precipitate.
[0037] 3. Methodological Verification
[0038] 3.1 Specificity Test
[0039] Blank Test: Dissolve 3.0 g of sodium sulfide in 25.0 ml of water, shake well, let stand overnight, filter through filter paper and then filter through a 0.22 μm filter membrane. Centrifuge the filtrate at a rate of 4000 rpm for 10 min, and take the supernatant as the blank solution. Take two 5-ml portions of the blank solution and place them in colorimetric tubes respectively. Add 2 ml of water to one portion and 2 ml of saturated ammonium oxalate solution to the other portion, let stand for 5 minutes, and observe the phenomenon.
[0040] Phenomenon: Both solutions are clear.
[0041] Test of Test Sample: Dissolve 3.0 g of sodium sulfide in 15.0 ml of water, dissolve 0.50 g of ferrous gluconate in 10.0 ml of water, mix the two solutions, shake well, let stand overnight, filter through filter paper and then filter through a 0.22 μm filter membrane. Centrifuge the filtrate at a rate of 4000 rpm for 10 min, and take the supernatant as the test sample solution. Take two 5-ml portions of the test sample solution and place them in colorimetric tubes respectively. Add 2 ml of water to one portion and 2 ml of saturated ammonium oxalate solution to the other portion, let stand for 5 minutes, and observe the phenomenon.
[0042] Phenomenon: Both solutions are clear. It shows that sodium sulfide can effectively remove ferrous ions, and the subsequent addition of ammonium oxalate will not produce precipitation, which does not affect the detection and judgment of calcium ions.
[0043] Blank Spike Test: Dissolve 3.0 g of sodium sulfide in 24.50 ml of water, add 0.50 ml of calcium control solution (calcium concentration is 0.20 mg / mL), the spiked amount is 0.05 mg, shake well, let stand overnight, filter through filter paper and then filter through a 0.22 μm filter membrane. Centrifuge the filtrate at a rate of 4000 rpm for 10 min, and take the supernatant as the blank spike solution. Take two 5-ml portions of the blank spike solution and place them in colorimetric tubes respectively. Add 2 ml of water to one portion and 2 ml of saturated ammonium oxalate solution to the other portion, let stand for 5 minutes, and observe the phenomenon.
[0044] Phenomenon: The solution is clear when adding water, and precipitation appears when adding ammonium oxalate solution. It shows that sodium sulfide can effectively remove ferrous ions without removing a small amount of calcium ions at the same time. After treatment, calcium ions can exist in the solution, and ammonium oxalate can be used to effectively detect it.
[0045] Spiked Test Sample Experiment: Dissolve 0.50 g of ferrous gluconate in 9.5 ml of water, add 0.50 ml of calcium control solution (calcium concentration is 0.20 mg / mL), the spiked amount is 0.05 mg, and the spiked amount corresponds to 0.02% of the ferrous gluconate content. Dissolve 3.0 g of sodium sulfide in 15.0 ml of water, mix the two solutions, shake well, let stand overnight, filter with filter paper and then filter with a 0.22 μm filter membrane. Centrifuge the filtrate at a rate of 4000 rpm for 10 min, and take the supernatant as the 0.02% spiked test sample solution. Take two portions of 5 ml of the 0.02% spiked test sample solution and place them in colorimetric tubes respectively. Add 2 ml of water to one portion and 2 ml of saturated ammonium oxalate solution to the other portion, let stand for 5 minutes, and observe the phenomenon.
[0046] Phenomenon: The solution is clear when water is added, and a precipitate appears when ammonium oxalate solution is added. In this method, the sample amount is 0.5 g, and calcium ions with a spiked amount of 0.05 mg can be detected. 0.05 mg of calcium is equivalent to 0.02% of calcium in the sample. That is, this method can detect 0.02% of calcium in the sample, and the detection sensitivity is not lower than the method sensitivity of the current Chinese Pharmacopoeia (see "2.1 Calcium Detection Limit" for details).
[0047] Conclusion: This method has good specificity. Sodium sulfide can effectively remove ferrous ions but will not remove a small amount of calcium ions. The calcium ions in the sample can be effectively detected, and the detection sensitivity is not lower than 0.02%.
[0048] 3.2 Repeatability Test
[0049] Dissolve 0.50 g of ferrous gluconate in 9.5 ml of water, add 0.50 ml of calcium control solution (calcium concentration is 0.20 mg / mL), the spiked amount is 0.05 mg, and the spiked amount corresponds to 0.02% of the ferrous gluconate content. Dissolve 3.0 g of sodium sulfide in 15.0 ml of water, mix the two solutions, shake well, let stand overnight, filter with filter paper and then filter with a 0.22 μm filter membrane. Centrifuge the filtrate at a rate of 4000 rpm for 10 min, and take the supernatant as the 0.02% spiked test sample solution. The above operations are carried out in six replicates. For each of the above, take two portions of 5 ml of the 0.02% spiked test sample solution and place them in colorimetric tubes respectively. Add 2 ml of water to one portion and 2 ml of saturated ammonium oxalate solution to the other portion, let stand for 5 minutes, and observe the phenomenon.
[0050] Phenomenon: The solutions of the six spiked test sample solutions are clear when water is added, and precipitates appear when ammonium oxalate solution is added.
[0051] 4. Comparison between the New and Old Methods
[0052] 4.1 New Method:
[0053] Dissolve 3.0 g of sodium sulfide in 15.0 ml of water, and dissolve 0.50 g of ferrous gluconate in 10.0 ml of water. Mix the two solutions, shake well, let stand overnight, filter through filter paper and then filter through a 0.22 μm filter membrane. Centrifuge the filtrate at a rate of 4000 rpm for 10 min, and take the supernatant as the test solution. Take two 5-ml portions of the test solution and place them in colorimetric tubes. Add 2 ml of water to one portion and 2 ml of saturated ammonium oxalate solution to the other portion. Let stand for 5 minutes and observe the phenomenon.
[0054] Phenomenon: If the calcium salt in ferrous gluconate meets the requirements, both solutions are clear; if the calcium salt in ferrous gluconate does not meet the requirements, the solution with added water is clear, and a precipitate appears when ammonium oxalate solution is added. It can be judged whether there is calcium salt in the sample.
[0055] 4.2 Detection method for calcium salt of ferrous gluconate in ChP 2020 edition:
[0056] Take 2.0 g of this product, dissolve it in 100 ml of water, and divide it into two equal parts: add 5 ml of ammonium oxalate test solution to one part and add 5 ml of water to the other part. Let stand for 5 minutes and observe the phenomenon.
[0057] Phenomenon: Regardless of whether the calcium salt in ferrous gluconate meets the requirements, the phenomenon is that the solution with added water is clear, and a precipitate appears when ammonium oxalate solution is added. It is impossible to judge whether the sample contains calcium salt.
[0058] The above embodiments are the preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.
Claims
1. A method for checking calcium salts in ferrous gluconate, characterized in that, it comprises the following steps: (1) Removal of ferrous salts: Dissolve sodium sulfide and ferrous gluconate in water, mix the two solutions, shake well, let stand for sufficient reaction, remove the precipitate, and take the supernatant as the test solution; (2) Checking of calcium salts: Take two portions of the test solution and place them in colorimetric tubes respectively. Add water to one portion and saturated ammonium oxalate solution to the other portion, let stand. If the two solutions are equally clear, it indicates that the calcium salts in ferrous gluconate are within a certain limit.
2. The method for checking calcium salts in ferrous gluconate according to claim 1, characterized in that: The specific method of step (1) is to dissolve 3.0 g of sodium sulfide in 15.0 ml of water, dissolve 0.50 g of ferrous gluconate in 10.0 ml of water, mix the two solutions, shake well, let stand for sufficient reaction, remove the precipitate, and take the supernatant as the test solution.
3. The method for checking calcium salts in ferrous gluconate according to claim 1 or 2, characterized in that: The method for removing the precipitate in step (1) is to filter first with filter paper and a filter membrane, and then centrifuge.
4. The method for checking calcium salts in ferrous gluconate according to claim 3, characterized in that: The filter membrane is a 0.22 μm filter membrane.
5. The method for checking calcium salts in ferrous gluconate according to claim 3, characterized in that: The centrifugation rate is 4000 rpm and the centrifugation time is 10 min.
6. The method for checking calcium salts in ferrous gluconate according to claim 1, characterized in that: The specific checking method of step (2) is: Take two 5-ml portions of the test solution and place them in colorimetric tubes respectively. Add 2 ml of water to one portion and 2 ml of saturated ammonium oxalate solution to the other portion, let stand for 5 minutes. If the two solutions are equally clear, it indicates that the calcium salts in ferrous gluconate meet the requirements (within 0.02%).