Method for detecting content of heavy metals in edetate disodium
By optimizing the detection conditions using an inductively coupled plasma mass spectrometer (ICP-MS), the problem of insufficient accuracy and sensitivity of the detection of heavy metal content in disodium yedate is solved, and efficient and accurate multi-element simultaneous detection effect is achieved.
Patent Information
- Application Number
- CN202411578696.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-07
- Publication Date
- 2025-02-14
AI Technical Summary
In the prior art, the detection of heavy metal content in disodium yideate has problems such as incomplete carbonization, interference in complexation, complicated operation and insufficient sensitivity, resulting in inaccurate detection results.
Inductively coupled plasma mass spectrometer (ICP-MS) is used for detection. By optimizing instrument conditions and selecting appropriate internal standard liquid, accurate, fast and multi-element simultaneous detection of heavy metals such as lead, mercury, copper, zinc and other elements are achieved.
It improves the accuracy and sensitivity of the detection, solves the problems of incomplete carbonization, interference in complexation, complicated operation and insufficient sensitivity in traditional methods, and significantly improves the detection efficiency and accuracy.
Abstract
Description
Technical Field
[0001] The invention belongs to the field of medical technology, and particularly relates to a method for detecting heavy metal content in disodium edetate. Background Art
[0002] Disodium EDTA, as an important pharmaceutical excipient, is widely used in the pharmaceutical field because it can complex with most heavy metals except alkali metals. In actual use, disodium EDTA is not only used as a complexing agent, but also often used as an antioxidant synergist and stabilizer. Especially in injection, it can complex with possible harmful heavy metal impurities, especially lead, mercury, copper, zinc, etc., to make the heavy metals inactive, thereby indirectly playing the role of stabilizer and antioxidant.
[0003] However, in the production and application of disodium edetate, accurate detection of heavy metal content has always been a technical problem. At present, common heavy metal detection methods, such as the method used in the Chinese Pharmacopoeia, mainly rely on carbonizing the sample with sulfuric acid and then performing color development and colorimetry. However, this method has some problems in actual operation:
[0004] Incomplete carbonization: During the sample carbonization process, the volatilization of sulfuric acid and the complexation of heavy metals by disodium edetate may lead to incomplete sample carbonization. This will affect the subsequent colorimetric reaction and make the test results different from the actual situation.
[0005] Complexation interference: The complexation of disodium edetate with heavy metals not only exists in the sample processing process, but may also affect the subsequent color development reaction. Some heavy metals may complex with unreacted disodium edetate, resulting in inaccurate colorimetric results.
[0006] Complicated operation: Traditional heavy metal detection methods are cumbersome and require multiple treatments and color development reactions, which is not only time-consuming and labor-intensive, but may also introduce operational errors.
[0007] Insufficient sensitivity: For the detection of trace heavy metals, traditional methods may not meet the requirements of high sensitivity, resulting in the inability to accurately determine the extremely low concentration of heavy metals in the sample.
[0008] In order to solve the above problems and improve the detection accuracy and sensitivity of heavy metal content in disodium edetate, the present invention proposes a new detection method. The method uses an inductively coupled plasma mass spectrometer (ICP-MS) for detection, and by optimizing instrument conditions, accurate, rapid, and multi-element simultaneous detection of heavy metals such as lead, mercury, copper, and zinc is achieved. This method not only solves the problems of incomplete carbonization, complex interference, cumbersome operation, and insufficient sensitivity in traditional methods, but also greatly improves detection efficiency and accuracy, providing strong technical support for the production and application of disodium edetate. Summary of the invention
[0009] The invention aims to provide a method for detecting the content of heavy metals in disodium edetate. The method is simple and accurate in operation, has good precision and repeatability, and high sensitivity.
[0010] In order to achieve the above object, the present invention provides the following technical solutions:
[0011] A method for detecting heavy metal content in disodium edetate comprises the following steps:
[0012] S1, prepare internal standard solution;
[0013] S2, pretreating disodium edetate to obtain a test solution;
[0014] S3, without adding disodium edetate, processing according to step S2 to obtain a blank solution;
[0015] S4, preparing a standard curve solution of heavy metals to be tested;
[0016] S5. Use inductively coupled plasma mass spectrometry to analyze the test solution, blank solution, and standard curve solution of the heavy metal to be tested, and perform data analysis.
[0017] Preferably, the internal standard solution is a rare earth metal solution.
[0018] Preferably, the rare earth metal is Rh, Bi or Ge.
[0019] The inventor found that the accuracy and sensitivity of the measuring method can be improved by selecting Rh, Bi, and Ge as the rare earth metal configuration internal standard solution. This may be because on the one hand, by adding the internal standard element of known concentration, the measurement error caused by factors such as instrument performance and sample matrix can be corrected, thereby improving the accuracy of detection. On the other hand, the selection of the internal standard element is usually close to the position of the measured element on the mass spectrum, which can minimize polyatomic interference and matrix effect, and improve the sensitivity of detection. For the heavy metal content in the detection method disodium edetate required by the present invention, the heavy metals that may exist in disodium edetate include lead, mercury, copper and zinc, etc., by forming complexes with these heavy metals, prompting it to be discharged from the body, reaching the therapeutic effect of treating heavy metal poisoning. And among lead, mercury, copper and zinc, the position of lead and Bi on the mass spectrum is the closest, the position of mercury and Rh on the mass spectrum is the closest, and the position of copper and zinc and Ge on the mass spectrum is the closest, so for detecting the heavy metals in disodium edetate, the internal standard rare earth metal selects Rh, Bi, and Ge. While improving the sensitivity, it also avoids the influence of excessive metal elements in the internal standard liquid on the detection results, thereby improving the accuracy.
[0020] Preferably, the solvent of the internal standard solution is a nitric acid aqueous solution with a mass fraction of 1% to 10%.
[0021] Preferably, the internal standard solution contains rare earth metals, and the concentration of the rare earth metals is 100-1500 μg / mL.
[0022] The specific operation steps of step S2 are: mixing hydrochloric acid with a mass concentration of 30-33%, nitric acid with a mass concentration of 65-68% and water in a volume ratio of 1: (2.2-2.5): 2 to obtain a digestion solution, adding 20-30 mL of the digestion solution for every 0.1 g of the vanadium-chromium-titanium alloy, leaving it for 1-2 days, pre-digesting it at 90-100° C. for 1-2 hours, and then step-raising the temperature three times; then lowering the temperature to 80-85° C., adding hydrofluoric acid with a mass concentration of 50-53%, adding 1.5-2 mL of hydrofluoric acid for every 0.2 g of the vanadium-chromium-titanium alloy, maintaining the temperature for secondary digestion for 1-2 hours, and finally raising the temperature to 90-95° C., adding nitric acid with a mass concentration of 60-63%, adding 1.5-2 mL of nitric acid with a mass concentration of 60-63% for every 0.2 g of the vanadium-chromium-titanium alloy, digesting it three times for 1-2 hours, and cooling it to obtain a test solution.
[0023] Preferably, the specific steps of the three-step heating are: heating to 120-130°C at a rate of 8-12°C / min, and keeping warm for 3-7 minutes at a pressure of 800-1200 kPa; heating to 150-160°C at a rate of 8-12°C / min, and keeping warm for 8-15 minutes at a pressure of 2500-3500 kPa; heating to 180-190°C at a rate of 8-12°C / min, and keeping warm for 20-30 minutes at a pressure of 4800-5200 kPa.
[0024] The commonly used digestion method in the prior art is to use nitric acid combined with a gradient temperature increase to digest, but it is found in the test process that the effect is not ideal and the accuracy of the test result is not high. The analysis is that there are the following reasons: disodium edetate can form a stable chelate with a variety of metal ions. During the digestion process, even if there is a strong acid such as nitric acid, disodium edetate may also be closely combined with the metal ions in the sample, hindering the complete release of these metal ions. In this case, even if high-temperature digestion is performed, some metal ions may still be fixed in the chelate, causing the actual measured value to be lower than the true value. At the same time, disodium edetate may decompose under high temperature conditions, especially in a strong acid environment. If the temperature is improperly controlled during the digestion process, disodium edetate may decompose, and the released metal ions may react with other components in the sample again to form new compounds, thereby affecting the final measurement results. In particular, the EDTA disodium salt prepared by the direct neutralization method of EDTA and sodium hydroxide may contain unreacted EDTA or other impurities, which may competitively chelate with metal ions during the digestion process, affecting the complete release of metal ions. The invention uses different acids to digest disodium edetate, so that heavy metal ions can be completely released, and the accuracy of the result is higher. At the same time, the gradient acid hydrolysis of the invention can be combined with a relatively low gradient temperature increase, which can ensure complete digestion and avoid the re-combination of disodium edetate with heavy metals after decomposition due to high temperature, thereby affecting the accuracy.
[0025] The inventor found that by microwave digestion of disodium edetate and combining three step heating, not only the accuracy and sensitivity of the measuring method can be improved. This may be because by gradually heating, on the one hand, the temperature of the sample can be gradually increased, so that the organic matter and inorganic matter in the sample are gradually decomposed at different temperature stages, thereby improving the digestion efficiency, helping to ensure that the heavy metal elements can be fully released into the solution, and improving the accuracy of detection. On the other hand, the violent reaction caused by the sudden decomposition of the sample at high temperature can be avoided, and the interference and error caused by sample splashing, container rupture, etc. can be reduced. At the same time, step heating also helps to reduce the interference of other components in the sample and improve the sensitivity of detection. And applying a certain pressure while heating can promote the release of gas in the sample and the mixing of solution, further improving the digestion efficiency. At the same time, pressure can also affect the ionization degree and stability of the heavy metal elements in the solution, thereby affecting the sensitivity and accuracy of detection.
[0026] Preferably, the standard stock solution of the heavy metal to be measured is an aqueous nitric acid solution of the heavy metal to be measured.
[0027] Preferably, the mass fraction of nitric acid in the nitric acid aqueous solution is 1% to 10%.
[0028] Preferably, the heavy metals to be detected include one or more of lead, mercury, copper, zinc, cadmium, chromium and arsenic.
[0029] Preferably, in the aqueous nitric acid solution of the heavy metals to be detected, the concentration of each heavy metal element to be detected is 0-50 μg / L.
[0030] The conditions of the inductively coupled plasma mass spectrometer are set as follows: radio frequency power: 1250-1600 W; plasma flow rate: 14-16 L / min; auxiliary gas flow rate: 0.8-0.9 L / min; carrier gas flow rate: 0.9-1.1 L / min; helium flow rate: 4.3-5.5 L / min; peristaltic pump speed: 0.1-0.5 r / s; nebulizer temperature 2-4°C; repeated collection times: 3 times; both the sampling cone and the intercepting cone are nickel cones; sampling cone aperture: 0.9-1.0 mm; intercepting cone aperture: 0.4-0.6 mm; sampling depth is 9-11 mm; scanning times: 90-100 times.
[0031] The inventors found that by setting the conditions of the inductively coupled plasma mass spectrometer, the accuracy and sensitivity of the detection method can be further improved. Controlling the radio frequency power ensures the generation and transmission efficiency of ions, thereby ensuring the stability of the plasma state, and then ensuring the accuracy and sensitivity of the detection results. The size of the plasma flow determines the density and stability of the plasma. Insufficient flow may cause unstable plasma flames, while excessive flow may dilute sample ions and reduce detection sensitivity. The carrier gas flow directly affects the transmission speed and efficiency of the sample. Too low flow may cause poor sample transmission, while too high flow may accelerate the diffusion and loss of ions, affecting the accuracy of the detection results.
[0032] The specific test method of step S5 is as follows: the internal standard injection tube of the inductively coupled plasma mass spectrometer is always inserted into the internal standard solution, the sample tube of the instrument is inserted into the standard curve solution of the heavy metal to be measured, and the standard curve is drawn. The sample tube of the instrument is inserted into the test solution, and the concentration is calculated from the standard curve. The blank solution is measured under the same analytical conditions for blank correction.
[0033] Compared with the prior art, the advantages and beneficial effects of the present invention are:
[0034] 1. The present invention provides a method for detecting the content of heavy metals in disodium edetate, which can not only simultaneously and quickly detect the content of heavy metals such as lead, mercury, copper, zinc, etc. in disodium edetate, but also greatly improves the detection efficiency and accuracy, and provides strong technical support for the production and application of disodium edetate.
[0035] 2. The present invention selects Rh, Bi, and Ge as rare earth metals to configure the internal standard solution, which can improve the accuracy and sensitivity of the measurement method.
[0036] 3. The present invention can not only improve the accuracy and sensitivity of the measurement method by using microwave digestion of disodium edetate combined with three-step temperature increase.
[0037] 4. The present invention can further improve the accuracy and sensitivity of the detection method by setting the conditions of the inductively coupled plasma mass spectrometer. DETAILED DESCRIPTION
[0038] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0039] The disodium edetate used in the present invention is purchased from Hangzhou Liren Pharmaceutical Co., Ltd. and is prepared by direct neutralization of EDTA and sodium hydroxide.
[0040] Example 1
[0041] This embodiment provides a method for detecting heavy metal content in edetate disodium, the steps are:
[0042] S1, prepare internal standard solution;
[0043] S2, pretreating disodium edetate to obtain a test solution;
[0044] S3, without adding disodium edetate, processing according to step S2 to obtain a blank solution;
[0045] S4, preparing a standard curve solution of heavy metals to be tested;
[0046] S5. Use inductively coupled plasma mass spectrometry to analyze the test solution, blank solution, and standard curve solution of the heavy metal to be tested, and perform data analysis.
[0047] The internal standard solution is a rare earth metal solution.
[0048] The rare earth metals are Rh, Bi and Ge.
[0049] The solvent of the internal standard solution is a nitric acid aqueous solution with a mass fraction of 5%.
[0050] The internal standard solution contains rare earth metals, and the concentration of the rare earth metals is 1000 μg / mL.
[0051] The specific operation steps of step S2 are: mixing hydrochloric acid with a mass concentration of 32%, nitric acid with a mass concentration of 67% and water in a volume ratio of 1:2.4:2 to obtain a digestion solution, adding 25 mL of the digestion solution to every 0.1 g of vanadium-chromium-titanium alloy, leaving it for 1.5 days, pre-digesting it at 95° C. for 1.6 hours, and then step-raising the temperature three times; then lowering the temperature to 82° C., adding hydrofluoric acid with a mass concentration of 51%, adding 1.7 mL of hydrofluoric acid to every 0.2 g of vanadium-chromium-titanium alloy, maintaining the temperature for a second digestion for 1.5 hours, and finally raising the temperature to 92° C., adding a mass concentration of The nitric acid is 62%, and 1.7 mL of nitric acid with a mass concentration of 62% is added to every 0.2 g of vanadium-chromium-titanium alloy. The mixture is digested for 1.5 h three times and cooled to obtain the test solution. The specific steps of the three step-by-step heating are: heating to 125°C at a rate of 10°C / min, and keeping warm for 5 min at a pressure of 900 kPa; heating to 155°C at a rate of 10°C / min, and keeping warm for 10 min at a pressure of 3000 kPa; heating to 185°C at a rate of 10°C / min, and keeping warm for 25 min at a pressure of 5000 kPa.
[0052] The standard stock solution of the heavy metal to be measured is an aqueous solution of nitric acid of the heavy metal to be measured.
[0053] The mass fraction of nitric acid in the nitric acid aqueous solution is 5%.
[0054] The heavy metals to be measured are lead, mercury, copper and zinc.
[0055] In the aqueous nitric acid solution of the heavy metals to be measured, the concentrations of the heavy metal elements to be measured are 0.1, 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, and 50.0 μg / L, respectively.
[0056] The conditions of the inductively coupled plasma mass spectrometer are set as follows: RF power: 1400 W; plasma flow: 15 L / min; auxiliary gas flow rate: 0.85 L / min; carrier gas flow: 1.0 L / min; helium flow: 5.0 L / min; peristaltic pump speed: 0.3 r / s; nebulizer temperature 2°C; number of repeated collections: 3 times; both the sampling cone and the intercepting cone are nickel cones; sampling cone aperture: 1.0 mm; intercepting cone aperture: 0.5 mm; sampling depth is 10 mm; number of scans: 100 times.
[0057] The specific test method of step S5 is as follows: the internal standard injection tube of the inductively coupled plasma mass spectrometer is always inserted into the internal standard solution, the sample tube of the instrument is inserted into the standard curve solution of the heavy metal to be measured, and the standard curve is drawn. The sample tube of the instrument is inserted into the test solution, and the concentration is calculated from the standard curve. The blank solution is measured under the same analytical conditions for blank correction.
[0058] Referring to the method in the paper "Determination of 11 Metal Elements in Disodium Hydrogen Phosphate by ICP-MS" published by Shi Rong, the detection limit, repeatability relative standard deviation (repeatability RSD) and precision relative standard deviation (precision RSD) of each heavy metal element were tested. The lower the detection limit, the higher the sensitivity of the method; the RSD must be less than 10%. The smaller the value, the better the accuracy and precision of the method.
[0059] The results showed that the detection limit of lead was 0.0012μg / g, the repeatability RSD was 1.5%, and the precision RSD was 1.2%; the detection limit of mercury was 0.0010μg / g, the repeatability RSD was 0.1%, and the precision RSD was 0.5%; the detection limit of copper was 0.002μg / g, the repeatability RSD was 0.15%, and the precision RSD was 0.4%; the detection limit of zinc was 0.004μg / g, the repeatability RSD was 2.1%, and the precision RSD was 1.7%.
[0060] Example 2
[0061] The difference between this embodiment and embodiment 1 is that the internal standard solution contains rare earth metals, and the concentration of the rare earth metals is 100 μg / mL.
[0062] The results showed that the detection limit of lead was 0.0014μg / g, the repeatability RSD was 1.8%, and the precision RSD was 1.4%; the detection limit of mercury was 0.0013μg / g, the repeatability RSD was 0.2%, and the precision RSD was 0.6%; the detection limit of copper was 0.004μg / g, the repeatability RSD was 0.3%, and the precision RSD was 0.7%; the detection limit of zinc was 0.006μg / g, the repeatability RSD was 2.4%, and the precision RSD was 2.0%.
[0063] Comparative Example 1
[0064] The difference between this comparative example and Example 1 is that the rare earth metals are Sc, Lu, and Tb.
[0065] The results showed that the detection limit of lead was 0.0024μg / g, the repeatability RSD was 2.8%, and the precision RSD was 2.4%; the detection limit of mercury was 0.0028μg / g, the repeatability RSD was 0.9%, and the precision RSD was 1.4%; the detection limit of copper was 0.015μg / g, the repeatability RSD was 1.6%, and the precision RSD was 1.8%; the detection limit of zinc was 0.018μg / g, the repeatability RSD was 3.6%, and the precision RSD was 2.9%.
[0066] Comparative Example 2
[0067] The difference between this comparative example and Example 1 is that the rare earth metals are Sc, Rh, Bi, and Ge.
[0068] The results showed that the detection limit of lead was 0.002μg / g, the repeatability RSD was 2.1%, and the precision RSD was 1.8%; the detection limit of mercury was 0.0019μg / g, the repeatability RSD was 0.5%, and the precision RSD was 0.9%; the detection limit of copper was 0.009μg / g, the repeatability RSD was 0.8%, and the precision RSD was 1.1%; the detection limit of zinc was 0.011μg / g, the repeatability RSD was 2.7%, and the precision RSD was 2.1%.
[0069] Comparative Example 3
[0070] The difference between this comparative example and Example 1 is that the specific operation steps of step S2 are: after mixing disodium edetate and nitric acid, take it out after leaving it for 1 day, pre-digest it at 100°C for 1.5h, heat it to 230°C at a rate of 10°C / min, keep it warm for 30min, take it out after cooling, and obtain the test solution.
[0071] The results showed that the detection limit of lead was 0.0028μg / g, the repeatability RSD was 3.6%, and the precision RSD was 3.3%; the detection limit of mercury was 0.0032μg / g, the repeatability RSD was 2.2%, and the precision RSD was 2.8%; the detection limit of copper was 0.015μg / g, the repeatability RSD was 3.2%, and the precision RSD was 3.6%; the detection limit of zinc was 0.036μg / g, the repeatability RSD was 4.4%, and the precision RSD was 4.0%.
[0072] Comparative Example 4
[0073] The difference between this comparative example and Example 1 is that the conditions of the inductively coupled plasma mass spectrometer are set as: RF power: 1800W; plasma flow rate: 15L / min; auxiliary gas flow rate: 0.85L / min; carrier gas flow rate: 1.0L / min; helium flow rate: 5.0L / min; peristaltic pump speed: 0.3r / s; nebulizer temperature 2°C; number of repeated collections: 3 times; both the sampling cone and the intercepting cone are nickel cones; sampling cone aperture: 1.0mm; intercepting cone aperture: 0.5mm; sampling depth is 10mm; number of scans: 100 times.
[0074] The results showed that the detection limit of lead was 0.002μg / g, the repeatability RSD was 2.4%, and the precision RSD was 2.8%; the detection limit of mercury was 0.0022μg / g, the repeatability RSD was 0.8%, and the precision RSD was 1.9%; the detection limit of copper was 0.009μg / g, the repeatability RSD was 0.9%, and the precision RSD was 1.5%; the detection limit of zinc was 0.011μg / g, the repeatability RSD was 3.3%, and the precision RSD was 3.2%.
[0075] Comparative Example 5
[0076] The difference between this comparative example and Example 1 is that the conditions of the inductively coupled plasma mass spectrometer are set as: RF power: 1400W; plasma flow rate: 18L / min; auxiliary gas flow rate: 0.85L / min; carrier gas flow rate: 1.0L / min; helium flow rate: 5.0L / min; peristaltic pump speed: 0.3r / s; nebulizer temperature 2°C; number of repeated collections: 3 times; both the sampling cone and the intercepting cone are nickel cones; sampling cone aperture: 1.0mm; intercepting cone aperture: 0.5mm; sampling depth is 10mm; number of scans: 100 times.
[0077] The results showed that the detection limit of lead was 0.0019μg / g, the repeatability RSD was 1.7%, and the precision RSD was 1.4%; the detection limit of mercury was 0.0024μg / g, the repeatability RSD was 0.3%, and the precision RSD was 0.9%; the detection limit of copper was 0.007μg / g, the repeatability RSD was 0.4%, and the precision RSD was 0.8%; the detection limit of zinc was 0.01μg / g, the repeatability RSD was 2.7%, and the precision RSD was 2.1%.
[0078] Comparative Example 6
[0079] The difference between this embodiment and embodiment 1 is that the specific steps of the three step heating are: heating to 120°C at a rate of 8°C / min, and keeping warm for 3 minutes at a pressure of 800 kPa; heating to 160°C at a rate of 8°C / min, and keeping warm for 8 minutes at a pressure of 2500 kPa; heating to 220°C at a rate of 8°C / min, and keeping warm for 20 minutes at a pressure of 4800 kPa.
[0080] The results showed that the detection limit of lead was 0.0022μg / g, the repeatability RSD was 2.9%, and the precision RSD was 2.2%; the detection limit of mercury was 0.0029μg / g, the repeatability RSD was 0.9%, and the precision RSD was 1.4%; the detection limit of copper was 0.015μg / g, the repeatability RSD was 1.8%, and the precision RSD was 1.9%; the detection limit of zinc was 0.020μg / g, the repeatability RSD was 3.9%, and the precision RSD was 2.8%.
[0081] Comparative Example 7
[0082] The difference between this comparative example and Example 1 is:
[0083] The specific operation steps of step S2 are: mixing hydrofluoric acid with a mass concentration of 51%, nitric acid with a mass concentration of 67% and water in a volume ratio of 1.7:1.7:2 to obtain a digestion solution, adding 25 mL of the digestion solution for every 0.1 g of the vanadium-chromium-titanium alloy, leaving it for 1.5 days, pre-digesting it at 95° C. for 1.6 hours, and then step-raising the temperature three times; then lowering the temperature to 82° C., adding hydrochloric acid with a mass concentration of 32%, adding 1.7 mL of hydrochloric acid for every 0.2 g of the vanadium-chromium-titanium alloy, maintaining the temperature for a second digestion for 1.5 hours, and finally raising the temperature to 92° C., adding nitric acid with a mass concentration of 55%, adding 1.7 mL of nitric acid with a mass concentration of 55% for every 0.2 g of the vanadium-chromium-titanium alloy, digesting it three times for 1.5 hours, and cooling it to obtain the test solution.
[0084] The results showed that the detection limit of lead was 0.0024μg / g, the repeatability RSD was 3.2%, and the precision RSD was 3.1%; the detection limit of mercury was 0.0030μg / g, the repeatability RSD was 2.0%, and the precision RSD was 2.4%; the detection limit of copper was 0.012μg / g, the repeatability RSD was 3.0%, and the precision RSD was 3.1%; the detection limit of zinc was 0.034μg / g, the repeatability RSD was 4.1%, and the precision RSD was 3.8%.
[0085] According to statistics, the method for detecting the heavy metal content in disodium edetate described in Examples 1 to 2 of the present invention detects the contents of four heavy metals, lead, mercury, copper and zinc, in disodium edetate, with a low detection limit, indicating high sensitivity, and the repeatability RSD and precision RSD are not only lower than 10%, but even lower than 3%, indicating that the detection method has good accuracy and precision.
[0086] Comparative Example 1 does not use the three rare earth metals described in the present invention, Comparative Example 2 adds the rare earth metal Sc that does not belong to the present invention, Comparative Example 3 does not use three-step heating, Comparative Example 4 has too large radio frequency power, and Comparative Example 5 has too high plasma flow. The sensitivity, accuracy, and precision of the detection method are all low. Therefore, the heavy metal content detection method in disodium edetate described in the present invention is simple and accurate to operate, has good precision and repeatability, and has high sensitivity.
[0087] In Comparative Example 6, the temperature of the gradient heating is too high, and the sensitivity, accuracy and precision of the detection method are all reduced. In Comparative Example 7, a different digestion method is used, and the sensitivity, accuracy and precision of the detection method are all reduced, indicating that the acid used in the gradient digestion and the temperature of the gradient heating have an effect on the detection of heavy metal content in disodium edetate prepared by the direct neutralization method.
[0088] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.
Claims
1. A method for detecting heavy metal content in disodium edetate, characterized in that: The following steps are involved: S1, prepare internal standard solution; S2, pretreating disodium edetate to obtain a test solution; S3, without adding disodium edetate, processing according to step S2 to obtain a blank solution; S4, preparing a standard curve solution of heavy metals to be tested; S5. Analyze the test solution, blank solution, and standard curve solution of the heavy metal to be tested using an inductively coupled plasma mass spectrometer, and perform data analysis; The internal standard solution is a rare earth metal solution; The rare earth metals are Rh, Bi, and Ge; The internal standard solution contains rare earth metals, and the concentration of the rare earth metals is 100-1500 μg / mL; The specific operation steps of step S2 are: mixing hydrochloric acid with a mass concentration of 30-33%, nitric acid with a mass concentration of 65-68% and water in a volume ratio of 1: (2.2-2.5): 2 to obtain a digestion solution, adding 20-30 mL of the digestion solution to every 0.1 g of vanadium-chromium-titanium alloy, leaving it for 1-2 days, pre-digesting it at 90-100° C. for 1-2 hours, and then step-raising the temperature three times; then lowering the temperature to 80-85° C., adding hydrofluoric acid with a mass concentration of 50-53%, adding 1.5-2 mL of hydrofluoric acid to every 0.2 g of vanadium-chromium-titanium alloy, maintaining the temperature for secondary digestion for 1-2 hours, and finally raising the temperature to 90-95° C., adding nitric acid with a mass concentration of 60-63%, adding 1.5-2 mL of nitric acid with a mass concentration of 60-63% to every 0.2 g of vanadium-chromium-titanium alloy, digesting it three times for 1-2 hours, and cooling it to obtain a test solution; The specific steps of the three-step temperature increase are: heating to 120-130°C at a rate of 8-12°C / min, and keeping warm for 3-7min at a pressure of 800-1200kPa; heating to 150-160°C at a rate of 8-12°C / min, and keeping warm for 8-15min at a pressure of 2500-3500kPa; heating to 180-190°C at a rate of 8-12°C / min, and keeping warm for 20-30min at a pressure of 4800-5200kPa; the conditions of the inductively coupled plasma mass spectrometer are set as follows: RF power rate: 1250~1600W; plasma flow rate: 14~16L / min; auxiliary gas flow rate: 0.8~0.9L / min; carrier gas flow rate: 0.9~1.1L / min; helium flow rate: 4.3~5.5L / min; peristaltic pump speed: 0.1~0.5r / s; nebulizer temperature 2~4℃; number of repeated collections: 3 times; sampling cone and intercepting cone are both nickel cones; sampling cone aperture: 0.9~1.0mm; intercepting cone aperture: 0.4~0.6mm; sampling depth is 9~11mm; number of scans: 90~100 times.
2. The method for detecting heavy metal content in edetate disodium according to claim 1, characterized in that: The solvent of the internal standard solution is a nitric acid aqueous solution with a mass fraction of 1% to 10%.
3. The method for detecting heavy metal content in edetate disodium according to claim 1, characterized in that: The standard curve solution of the heavy metal to be measured is an aqueous solution of nitric acid of the heavy metal to be measured.
4. The method for detecting heavy metal content in edetate disodium according to claim 3, characterized in that: The heavy metals to be detected include one or more of lead, mercury, copper, zinc, cadmium, chromium and arsenic.
5. The method for detecting heavy metal content in edetate disodium according to claim 4, characterized in that: In the aqueous nitric acid solution of the heavy metals to be measured, the concentration of each heavy metal element to be measured is 0-50 μg / L.
6. Application of the method for detecting heavy metal content in edetate disodium according to any one of claims 1 to 5 in the field of medical technology.