Method for determining lead salt in sulfadiazine zinc raw material

Abstract

The invention belongs to the technical field of medical chemical component detection, and discloses a method for determining lead salt in a sulfadiazine zinc raw material, which comprises the following steps: S1, measuring a lead single element standard solution, and diluting with a nitric acid solution to obtain a linear solution containing different concentrations of lead; s2, weighing a sample, and adding nitric acid for digestion and dissolution to obtain a sulfadiazine zinc test solution; s3, measuring the same amount of nitric acid in the step S2, and performing digestion and dissolution to obtain a sample blank solution; s4, respectively injecting the linear solutions in the step S1 into an atomic absorption spectrophotometer, and making standard koji according to a preset heating program; and S5, respectively injecting the sulfadiazine zinc test solution and the sample blank solution into an atomic absorption spectrophotometer, and determining the lead content in the sulfadiazine zinc according to a preset heating program. The problems that an existing method is low in sensitivity and cannot meet limit requirements are solved.

Description

Technical Field

[0001] The invention relates to the technical field of medical chemical component detection, in particular to a method for determining lead salt in sulfadiazine zinc raw material. Background Art

[0002] Sulfadiazine is a drug with significant antibacterial effects, and its unique zinc component can further enhance its antibacterial effect by destroying the DNA structure of bacteria. For burn patients, due to the large loss of zinc in the body, the use of sulfadiazine zinc can effectively replenish this key element, enhance the body's resistance to infection, and help wound healing. Therefore, sulfadiazine zinc has a dual effect, namely controlling infection and promoting wound healing.

[0003] Sulfadiazine zinc ointment is used to prevent and treat wound infection secondary to second-degree and third-degree burns. According to the ICH Q3D (R2) guidelines, drugs that act directly on the dermis (such as second-degree and third-degree burns) are usually suitable for injection. The PDE (Permitted Daily Exposure) value of lead for injection is 5μg / day, so the daily lead intake limit should be 0.2ppm.

[0004] However, the current standard (Chinese Pharmacopoeia 2020 Edition Part II) for the determination of lead salts in sulfadiazine zinc raw materials is to take 2.0g of this product, add water and glacial acetic acid, heat and dissolve, and take the filtrate and add 5 drops of potassium chromate indicator solution. It must not be turbid. When conducting a sensitivity test, take 1ml of the lead standard solution (100μg / ml), add 5 drops of potassium chromate indicator solution, and it will show slight turbidity. The detection sensitivity is low, and the detection limit is 50ppm. It is difficult to reliably detect the minimum concentration of lead. The existing technical method is a colorimetric method, which has low sensitivity and cannot meet the limit requirements. Summary of the invention

[0005] The invention aims to provide a method for determining lead salt in sulfadiazine zinc raw material, so as to solve the problem that the existing method has low sensitivity and cannot meet the limit requirement.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] A method for determining lead salt in a sulfadiazine zinc raw material comprises the following steps:

[0008] S1. Prepare linear solutions of different concentrations

[0009] Measure the single element lead standard solution and dilute it with nitric acid solution to a linear solution containing different concentrations of lead, with nitric acid serving as the blank solution;

[0010] S2. Preparation of sulfadiazine zinc test solution

[0011] Weigh the sample, add nitric acid to digest and dissolve it, and after digestion and dissolution, obtain the sulfadiazine zinc test solution;

[0012] The digestion and dissolution steps are: pre-digestion by heating, cooling, then digestion according to the microwave digestion procedure, diluting with water and fixing the volume;

[0013] S3. Prepare sample blank solution

[0014] Take an equal amount of nitric acid from step S2, and perform digestion and dissolution according to the digestion and dissolution steps in step S2 to obtain a sample blank solution;

[0015] S4. Make a standard curve

[0016] The linear solutions of step S1 are respectively injected into an atomic absorption spectrophotometer, and a matrix modifier is precisely added. According to a predetermined temperature increase program, a linear regression is performed with absorbance as the ordinate and injection concentration as the abscissa to prepare a standard curve to obtain the relationship between lead concentration and absorbance;

[0017] S5. Determination of lead content in sulfadiazine zinc raw materials

[0018] The sulfadiazine zinc test solution obtained in step S2 and the sample blank solution obtained in step S3 are respectively injected into an atomic absorption spectrophotometer, and a matrix modifier is precisely added. The lead content in the sulfadiazine zinc is determined according to a predetermined temperature program and based on the standard curve of step S4.

[0019] Further, in step S1, the concentration of the nitric acid solution is 5%.

[0020] Further, in step S2, the microwave digestion procedure is: step one: heating temperature is 100°C, heating time is 2 min, step two: heating temperature is 120°C, heating time is 2 min, step three: heating temperature is 150°C, heating time is 5 min, step four: heating temperature is 180°C, heating time is 10 min, step five: heating temperature is 200°C, heating time is 30 min.

[0021] Further, in step S2, the temperature of the heating pre-digestion is 120°C and the time is 30 minutes.

[0022] Further, in step S4, the atomic absorption spectrophotometer uses a graphite furnace atomizer, and the matrix modifier is a solution containing 1% diammonium dihydrogen phosphate and 0.5% magnesium nitrate.

[0023] Further, in step S5, the predetermined heating program is: step one: temperature is 110°C, ramp-up time is 1s, holding time is 30s, and internal flow rate is 250ml / min; step two: temperature is 120°C, ramp-up time is 15s, holding time is 30s, and internal flow rate is 250ml / min; step three: temperature is 950°C, ramp-up time is 10s, holding time is 30s, and internal flow rate is 250ml / min; step four: temperature is 1600°C, ramp-up time is 0s, holding time is 5s, and internal flow rate is 0ml / min; step five: temperature is 2450°C, ramp-up time is 1s, holding time is 3s, and internal flow rate is 250ml / min.

[0024] The beneficial effects of the technical solution are:

[0025] The invention provides a method for determining lead salt in sulfadiazine zinc raw material. The method utilizes atomic absorption spectrophotometry, adjusts ashing temperature and atomization temperature in a graphite furnace heating program, and formulates a suitable digestion and dissolution program, so that the lead salt in the sulfadiazine zinc raw material can be accurately detected. Experiments prove that the method has good accuracy, specificity, linearity, quantitative limit, detection limit, injection precision and repeatability, and has high detection sensitivity. The detection limit can reach 0.2ppm, which can meet the detection of lead salt in the sulfadiazine zinc raw material. A solution containing 1% of ammonium dihydrogen phosphate and 0.5% of magnesium nitrate is added as a matrix modifier to avoid zinc-containing interference with lead determination, so that the detection result is more accurate. DETAILED DESCRIPTION

[0026] The present invention is further described in detail below in conjunction with the embodiments:

[0027] Example 1

[0028] A method for determining lead salt in a sulfadiazine zinc raw material comprises the following steps:

[0029] S1. Prepare linear solutions of different concentrations

[0030] Take 25 ml of nitric acid, add water to 500 ml, shake well, and obtain a blank solution (5% nitric acid solution); accurately measure 0.5 ml of lead single element standard solution (10.0 μg / ml), put it in a 50 ml volumetric flask, dilute to the scale with 5% nitric acid, shake well, and obtain a standard lead stock solution; take the blank solution as linear solution 1, and then accurately measure an appropriate amount of the standard lead stock solution, quantitatively dilute it with 5% nitric acid to prepare solutions containing about 5 ng / ml, 10 ng / ml, 20 ng / ml, 30 ng / ml, 40 ng / ml, and 50 ng / ml of lead per 1 ml, as linear solutions 2 to 7;

[0031] S2. Preparation of sulfadiazine zinc test solution

[0032] Take 0.2 g of the raw material sample of sulfadiazine zinc from manufacturer 1, accurately weigh it, place it in a polytetrafluoroethylene digestion tank, add 8 ml of concentrated nitric acid, pre-digest it at 120°C for 30 min, let it cool, cover the inner cover, tighten the outer cover, and digest and dissolve it according to the microwave digestion program. The microwave digestion program is shown in Table 1. Let it cool after digestion, slowly open the tank cover to vent, rinse the inner cover with a small amount of water, transfer it to a centrifuge tube with water, add water to 20 g, shake well, and obtain the sulfadiazine zinc test solution.

[0033] Table 1 Microwave digestion procedure

[0034] step Temperature / ℃ Insulation time / min 1 100 2 2 120 2 3 150 5 4 180 10 5 200 30

[0035] S3. Prepare sample blank solution

[0036] Take an equal amount of nitric acid from step S2, and perform digestion and dissolution according to the digestion and dissolution steps in step S2, i.e., pre-digest at 120° C. for 30 min, cool, cover with an inner cover, tighten the outer cover, perform microwave digestion according to a predetermined program, cool after digestion, slowly open the tank cover to vent, rinse the inner cover with a small amount of water, transfer to a centrifuge tube with water, add water to 20 g, shake well, and obtain a sample blank solution;

[0037] S4. Make a standard curve

[0038] The linear solutions 1-7 in step S1 were added to the graphite furnace atomizer respectively, with absorbance A as the ordinate and injection concentration C (ng·mL -1 ) was used as the horizontal axis for linear regression and a standard curve was drawn to obtain the relationship between lead concentration and absorbance; and the linear regression equation was A=0.0024C+0.0007, r=0.9993 (n=7), which shows that lead has a good linear relationship in the concentration range of 0-50 ng / ml.

[0039] S5. The sulfadiazine zinc test solution obtained in step S2 and the sample blank solution obtained in step S3 are added to the graphite furnace atomizer respectively, and the lead content in the sulfadiazine zinc is determined according to a predetermined heating program as shown in Table 2, and based on the standard curve of step S4. In step S4, it can be concluded that the relationship between absorbance and lead concentration is A=0.0024C+0.0007, r=0.9993 (n=7), r=0.9993 represents the correlation coefficient, indicating that there is a strong linear relationship between absorbance and concentration, n=7 represents the number of standard solutions used to establish the regression equation, specifically, the absorbance value A1 of the blank sample solution and the absorbance value A2 of the test solution are recorded, the corrected absorbance value is A2-A1, and the corrected absorbance value is converted into a concentration value based on the relationship between absorbance and lead concentration, i.e., the concentration value of lead in the test solution.

[0040] Table 2 Predetermined heating program

[0041] step Temperature / ℃ Ramp up time / s Maintaining time / s Internal flow / ml / min 1 110 1 30 250 2 130 15 30 250 3 950 10 30 250 4 1600 0 5 0 5 2450 1 3 250

[0042] The sample was tested according to the method of the present invention, and the result showed that no lead salt was detected in the sulfadiazine zinc raw material of manufacturer 1.

[0043] Embodiment 2:

[0044] The difference between this embodiment and embodiment 1 is:

[0045] 0.2 g of the sulfadiazine zinc raw material from manufacturer 2 was accurately weighed, and the other steps were the same as those in Example 1, which will not be repeated here. Results No lead salt was detected in the sulfadiazine zinc raw material from manufacturer 2.

[0046] Example 3

[0047] The blank solution (5% nitric acid solution) in step S2 of Example 1 was injected into an atomic absorption spectrophotometer (injection), and the solution had no absorption, indicating that the method had good specificity.

[0048] Example 4

[0049] The sample blank solution obtained in step S3 of Example 1 was taken and sampled 11 times continuously. The ratio of 3 times the standard deviation (3SD) of the 11 absorbances to the slope of the lead standard curve was taken as the detection concentration of lead, and the ratio of 10 times the standard deviation (10SD) of the 11 absorbances to the slope of the lead standard curve was taken as the quantitative concentration of lead. The results are shown in Table 3. This method can meet the needs of lead salt detection.

[0050] Table 3 Detection limit and quantification limit

[0051]

[0052] Example 5

[0053] The linear solution 4 (20 ng / ml) obtained in step S1 of Example 1 was accurately measured and injected 6 times continuously. The RSD of the absorbance is shown in Table 4. The results show that the injection precision of this method is good.

[0054] Table 4 Injection precision results

[0055]

[0056] Example 6

[0057] Six samples from the same batch of the sulfadiazine zinc raw material in Example 1 were accurately weighed, and the lead content was determined according to the method of Example 1. As a result, no lead was detected in the six samples, indicating that the method has good repeatability.

[0058] Example 7

[0059] Take 9 samples of the same batch of sulfadiazine zinc raw material in Example 1, accurately weigh them, and accurately add 0.2g, 0.4g and 0.6g of standard lead solution (1000ng / ml) equivalent to 50%, 100% and 150% of lead respectively, operate in the same way as the test solution, prepare 3 samples at each concentration level in parallel, and measure them respectively. The average recovery rate of 9 samples is 87.3%, and the RSD is 6.3%. The results are shown in Table 5, which shows that the accuracy of this method is good.

[0060] Table 5 Recovery results

[0061]

[0062] Combined with the measurement results of Example 1 and Example 2, according to the second method of atomic absorption spectrophotometry in 0406 of the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia, the impurity limit inspection method in the standard addition method is adopted. Prepare the test solution according to step S2 of Example 1; take an equal amount of the test solution, accurately add 1 ml of lead standard solution (accurately measure an appropriate amount of lead single element standard solution (1000 μg / ml), and quantitatively dilute with water to make a solution containing 0.4 μg / ml of lead per 1 ml) to prepare a reference solution, and compare the absorbance of the test solution (b) and the absorbance of the reference solution (a)-the absorbance of the test solution (b) according to the determination method of lead salt in the sulfadiazine zinc raw material in Example 1. When b<ab, it is determined that the result meets the requirements. As a result, 7 batches of samples from 2 manufacturers all met the requirements, and the results are shown in Table 6, indicating that the determination accuracy is good.

[0063] Table 6 Lead salt determination results

[0064]

[0065] Note: When the absorbance b value of the test solution in the above table is negative, it is calculated as "b=0".

[0066] In summary, the present invention provides a method for determining lead salt in sulfadiazine zinc raw material. The method utilizes atomic absorption spectrophotometry, adjusts the ashing temperature and the atomization temperature in the graphite furnace heating program, and formulates a suitable digestion and dissolution program, so that the lead salt in the sulfadiazine zinc raw material can be accurately detected. Experiments have proved that the method has good accuracy, specificity, linearity, quantitative limit, detection limit, injection precision, and repeatability, and has high detection sensitivity. The detection limit can reach 0.2ppm, which can meet the detection of lead salt in sulfadiazine zinc raw material; and a solution containing 1% diammonium phosphate and 0.5% magnesium nitrate is added as a matrix modifier to avoid zinc interference with lead determination, so that the detection result is more accurate.

[0067] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, several modifications and improvements can be made without departing from the technical solution of the present invention, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A method for determining lead salt in sulfadiazine zinc raw material, characterized in that, The following steps are involved: S1. Prepare linear solutions of different concentrations Measure the single element lead standard solution and dilute it with nitric acid solution to a linear solution containing different concentrations of lead, with nitric acid serving as the blank solution; S2. Preparation of sulfadiazine zinc test solution Weigh the sample, add nitric acid to digest and dissolve it, and after digestion and dissolution, obtain the sulfadiazine zinc test solution; The digestion and dissolution steps are: pre-digestion by heating, cooling, then digestion according to the microwave digestion procedure, diluting with water and fixing the volume; S3. Prepare sample blank solution Measure an equal amount of nitric acid in step S2, and perform digestion and dissolution according to the digestion and dissolution steps in step S2 to obtain a sample blank solution; S4. Make a standard curve The linear solutions of step S1 are respectively injected into an atomic absorption spectrophotometer, and a matrix modifier is precisely added. According to a predetermined temperature increase program, a linear regression is performed with absorbance as the ordinate and injection concentration as the abscissa to prepare a standard curve to obtain the relationship between lead concentration and absorbance; S5. Determination of lead content in sulfadiazine zinc raw materials The sulfadiazine zinc test solution obtained in step S2 and the sample blank solution obtained in step S3 are respectively injected into an atomic absorption spectrophotometer, and a matrix modifier is precisely added. The lead content in the sulfadiazine zinc is determined according to a predetermined temperature program and based on the standard curve of step S4.

2. The method for determining the lead salt in a sulfadiazine zinc raw material according to claim 1, wherein: In step S1, the concentration of the nitric acid solution is 5%.

3. The method for determining the lead salt in a sulfadiazine zinc raw material according to claim 1, wherein: In step S2, the microwave digestion procedure is: step 1: heating temperature is 100°C, heating time is 2 min, step 2: heating temperature is 120°C, heating time is 2 min, step 3: heating temperature is 150°C, heating time is 5 min, step 4: heating temperature is 180°C, heating time is 10 min, step 5: heating temperature is 200°C, heating time is 30 min.

4. The method for determining the lead salt in a sulfadiazine zinc raw material according to claim 1, wherein: In step S2, the pre-digestion temperature is 120°C and the time is 30 minutes.

5. The method for determining the lead salt in a sulfadiazine zinc raw material according to claim 1, characterized in that: In step S4, the atomic absorption spectrophotometer uses a graphite furnace atomizer, and the matrix modifier is a solution containing 1% diammonium dihydrogen phosphate and 0.5% magnesium nitrate.

6. The method for determining the lead salt in a sulfadiazine zinc raw material according to claim 1, characterized in that: In step S5, the predetermined heating program is: step one: temperature is 110°C, ramp-up time is 1s, holding time is 30s, and internal flow rate is 250ml / min; step two: temperature is 120°C, ramp-up time is 15s, holding time is 30s, and internal flow rate is 250ml / min; step three: temperature is 950°C, ramp-up time is 10s, holding time is 30s, and internal flow rate is 250ml / min; step four: temperature is 1600°C, ramp-up time is 0s, holding time is 5s, and internal flow rate is 0ml / min; step five: temperature is 2450°C, ramp-up time is 1s, holding time is 3s, and internal flow rate is 250ml / min.

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