Method for measuring radiochemical purity and iodine content of sodium iodide capsule for diagnosis by HPLC (high performance liquid chromatography)

Abstract

The invention relates to the technical field of iodide content detection, in particular to a method for determining radiochemical purity and iodine content of sodium iodide capsules for diagnosis by HPLC (High Performance Liquid Chromatography), which comprises the following steps: setting chromatographic conditions, and connecting a radioactive flow detector and an ultraviolet detector in series; preparing a disodium hydrogen phosphate solution, a glucose solution, a vitamin C solution, a first control solution, a potassium iodate solution, a second control solution, a carrier solution, a first sample solution, a second sample solution, a negative control solution and a test solution; and determining the radiochemical purity and iodide content of the first sample solution and the second sample solution in three batches based on the chromatographic conditions and the determination standard. According to the method, test parameters such as capsule sample analysis time, a pretreatment mode and a sample size are optimized, the radiochemical purity of the capsule is accurately determined, and the iodide content is controlled, so that the problem that main components cannot be accurately quantified and potential radioactive impurities cannot be detected by a traditional diagnosis sodium iodide [131I] capsule determination method is solved.

Description

Technical Field

[0001] This invention relates to the field of iodide content detection technology, and more particularly to an HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules. Background Technology

[0002] Iodine for diagnosis 131 I] Sodium iodide capsules are mainly used for thyroid imaging and thyroid function testing. Their mechanism of action is iodine [ 131 Sodium iodide is taken up and concentrated by the thyroid follicular epithelium, and the effect is measured in vitro using a thyroid function analyzer. Oral iodine […]. 131 I] Thyroid uptake after sodium bicarbonate capsules [ 131 [I] Rate is used to assess thyroid function. For radiopharmaceuticals, some radiochemical impurities can accumulate in the blood and non-target organs, affecting imaging results; therefore, control of radiochemical impurities is necessary. Radiochemical purity (hereinafter referred to as radiochemical purity) refers to the percentage of radionuclides existing in a specific chemical form in a radioactive sample. Therefore, radiochemical purity is one of the key parameters for judging the quality of radiopharmaceuticals.

[0003] For diagnostic iodine [ 131 The radiochemical purity determination method for sodium chloride capsules is described in both the Chinese Pharmacopoeia and the United States Pharmacopeia using paper chromatography, while the European Pharmacopoeia uses high-performance liquid chromatography. Domestic diagnostic iodine [ 131 Sodium chloride capsules have a strength of approximately several hundred thousand becquerels (Bq) per capsule, indicating low radioactivity. Determining radiochemical purity using paper chromatography typically requires repeated spotting and drying on chromatographic paper, with sample preparation time usually exceeding 30 minutes. Furthermore, different operators' spotting techniques can lead to issues such as peak tailing and peak bifurcation. The General Rules for the Determination of Radioactive Drugs in the Chinese Pharmacopoeia also clearly state that other validated analytical methods capable of effectively separating various radiochemical impurities (such as high-performance liquid chromatography) can also be used for the determination of radiochemical purity. Moreover, high-performance liquid chromatography features high sensitivity, high accuracy, high degree of instrument automation, and strong software compliance, making its use a future trend in radiochemical purity determination.

[0004] Iodine is used for diagnosis. 131 The radioactivity of sodium chloride capsules is low, and the determination method of the European Pharmacopoeia is directly used for the diagnostic use of iodine [I] within the validity period. 131 When the radiochemical purity of sodium chloride capsules was measured, the peak height response value of the main radioactive component was too low, below the limit of quantification, making it impossible to accurately quantify the main component and detect potential radioactive impurities. Summary of the Invention

[0005] The purpose of this invention is to provide an HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules, aiming to solve the problem that traditional methods for determining the radiochemical purity of diagnostic sodium iodide capsules cannot accurately quantify the main components and detect potential radioactive impurities.

[0006] To achieve the above objectives, the present invention provides an HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules, comprising the following steps;

[0007] Set chromatographic conditions and connect a radioactive flow detector and an ultraviolet detector in series;

[0008] Prepare disodium hydrogen phosphate solution, glucose solution, vitamin C solution, first control solution, potassium iodate solution, second control solution, carrier solution, first sample solution, second sample solution, negative control solution and test solution;

[0009] Based on the chromatographic conditions and judgment criteria, the radiochemical purity and iodide content of the first sample solution and the second sample solution were determined in three batches.

[0010] The chromatographic conditions include using a chromatographic column packed with octadecylsilane-bonded silica gel, a mobile phase of a 20:1 mixture of 5.85 g / L sodium chloride solution and acetonitrile, and ultrasonic removal of air bubbles after filtration through a 0.45 μm filter membrane.

[0011] The chromatographic conditions also include a column temperature of 25°C, an injection volume of 100 μL, a run time of 12 min, and isocratic elution at a flow rate of 1.5 mL / min.

[0012] The judgment criteria include that, in the radiochromatogram of the first sample solution, the radiochemical purity calculated by the normalization method of radioactive peak area should not be less than 95%, and the retention time of the main radioactive peak should not differ from the retention time of the iodide peak in the first control solution by more than ±10%.

[0013] The judgment criteria also include that in the ultraviolet chromatogram of the second sample solution, in the chromatogram of the negative control solution, all peaks must not have a retention time similar to that of the iodide ion peak in the first control solution, and in the chromatogram of the second control solution, the resolution between the iodide ion peak and the iodate ion peak should not be less than 2 and should not exceed the peak area corresponding to the iodide in the chromatogram of the first control solution, i.e., the iodide ion content ≤ 20 μg / particle.

[0014] This invention provides an HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules. The method involves setting chromatographic conditions and connecting a radioactive flow detector and an ultraviolet detector in series. It prepares disodium hydrogen phosphate solution, glucose solution, vitamin C solution, a first control solution, potassium iodate solution, a second control solution, a carrier solution, a first sample solution, a second sample solution, a negative control solution, and a test solution. Based on the chromatographic conditions and judgment criteria, the radiochemical purity and iodide content of the first and second sample solutions are determined in three batches. This method optimizes experimental parameters such as capsule sample analysis time, pretreatment method, and injection volume, accurately determining the radiochemical purity of the capsules and controlling the iodide content, thereby solving the problem of traditional diagnostic sodium iodide... 131 The sodium chloride capsule assay method has the problem of not being able to accurately quantify the main component and detect potential radioactive impurities. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 The above is an HPLC chromatogram of the excipients, where (a) is an antioxidant solution; (b) is a packing agent A solution; (c) is water; (d) is the mobile phase; (e) is a packing agent B solution; (f) is a negative control solution; (g) is a potassium iodate solution; and (h) is the first control solution.

[0017] Figure 2 This is an HPLC chromatogram of radiochemical purity determination (stability 0 days).

[0018] Figure 3 This is an HPLC chromatogram of radiochemical purity determination (stability 21 days).

[0019] Figure 4 These are HPLC chromatograms for specific determination, where (a) is a radiometric spectrum and (b) is an ultraviolet spectrum.

[0020] Figure 5 It is iodine. 131 I] Schematic diagram of the linearity and range of the compound.

[0021] Figure 6 This is a flowchart of the HPLC method for determining the radiochemical purity and iodine content of sodium iodide capsules for diagnostic purposes, provided by the present invention. Detailed Implementation

[0022] Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0023] Please see Figures 1 to 6 This invention provides an HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules, comprising the following steps;

[0024] S1 sets the chromatographic conditions, connecting the radioactive flow detector and the ultraviolet detector in series;

[0025] In this embodiment of the invention, an octadecylsilane-bonded silica gel column was used as the packing material; a mixed solution of 5.85 g / L sodium chloride solution (with 0.65 mL of n-octylamine added and pH adjusted to 7.0 with dilute phosphoric acid): acetonitrile = 20:1 (V:V) was used as the mobile phase, filtered through a 0.45 μm filter membrane and then ultrasonically removed to remove air bubbles; a radioactive flow detector (BGO detection cell, 150 μL) was connected in series with an ultraviolet detector (detection wavelength of 220 nm), the column temperature was 25 °C, the injection volume was 100 μL, the run time was 12 min, and isocratic elution was performed at a flow rate of 1.5 mL / min.

[0026] S2 prepares disodium hydrogen phosphate solution, glucose solution, vitamin C solution, first control solution, potassium iodate solution, second control solution, carrier solution, first sample solution, second sample solution, negative control solution, and test solution;

[0027] In this embodiment of the invention, the disodium hydrogen phosphate solution (filler A solution) is prepared by accurately weighing 0.37 g of disodium hydrogen phosphate into a 10 mL vial, adding 1 mL of sterile water for injection to dissolve it, allowing it to stand, and then filtering it through a 0.2 μm filter membrane for later use.

[0028] Glucose solution (filler B solution): Accurately weigh 15.5 mg of glucose into a 10 mL vial, accurately add 1 mL of sterile water for injection to dissolve it, let it stand, and then filter it through a 0.2 μm filter membrane for later use.

[0029] Vitamin C solution (antioxidant solution): Accurately weigh 0.10g of vitamin C into a 10mL vial, accurately add 1mL of sterile water for injection to dissolve it, let it stand, and then filter it through a 0.2μm filter membrane for later use.

[0030] First control solution: Accurately weigh 26.20 mg of potassium iodide into a 10 L volumetric flask, dissolve it in water, make up to volume and mix well to obtain the first control solution containing 2.62 mg / L of iodide.

[0031] Potassium iodate solution: Accurately weigh 24.50 mg of potassium iodate into a 10 L volumetric flask, dissolve in water, dilute to volume and mix well to obtain a potassium iodate solution containing 2.45 mg / L of potassium iodate.

[0032] Second control solution: Mix equal volumes of potassium iodate solution and first control solution to obtain the solution.

[0033] Carrier solution: Weigh 1.0g of potassium iodide, 2.0g of potassium iodate and 10.0g of sodium bicarbonate into a 1L volumetric flask, add water to make up to volume and mix well.

[0034] First sample solution: Dissolve the contents of 2 capsules in 2 mL of 10% phosphoric acid solution, shake thoroughly, and filter through a 0.2 μm syringe filter. Take an appropriate amount of the filtrate and add a certain volume of carrier solution to prepare the sample solution.

[0035] Second sample solution: Dissolve the contents of one capsule in 10 mL of water, shake thoroughly, and filter using a 0.2 μm needle filter.

[0036] Negative control solution: Iodine solution as used for diagnosis [ 131 The formulation and manufacturing process of sodium chloride capsules involves preparing iodine-free capsules using antioxidants, filler A, filler B, and other pharmaceutical excipients in a prescribed ratio. 131 I] Capsules of sodium chloride solution were used to prepare a negative control solution in the same manner as the second sample solution.

[0037] Test solution: Accurately measure an appropriate amount of iodine [ 131 I] Sodium chloride oral solution, iodine [ 131 I] Acid radical solution (ensuring impurity iodine [ 131 I] The iodine anion (approximately 1-5% of the overall radioactivity) was evenly dropped onto a blank capsule and left for 10 minutes to allow the iodine in the solution to […]. 131 I] compounds and iodine[ 131 I] The acid radicals are fully adsorbed onto the solid. Prepare the test solution in the same manner as the first sample solution.

[0038] S3 determined the radiochemical purity and iodide content of the first sample solution and the second sample solution in three batches based on the chromatographic conditions and judgment criteria.

[0039] In this embodiment of the invention, the determination criteria include that the radiochemical purity of the first sample solution, calculated by the normalization method of radioactive peak area, should not be less than 95%, and the retention time of the main radioactive peak should not differ from the retention time of the iodide peak in the first control solution by more than ±10%.

[0040] The judgment criteria also include that in the ultraviolet chromatogram of the second sample solution, in the chromatogram of the negative control solution, all peaks must not have a retention time similar to that of the iodide ion peak in the first control solution. In the chromatogram of the second control solution, the resolution between the iodide ion peak and the iodate ion peak should not be less than 2 and should not exceed the peak area corresponding to the iodide in the chromatogram of the first control solution, i.e., the iodide ion content should be ≤20μg / particle.

[0041] The calculation of iodide ion content is shown in equation (1):

[0042]

[0043] In the formula: S1 is the peak area of ​​the first control solution; S2 is the peak area of ​​iodide in the second sample solution; C is the concentration of iodide in the first control solution (mg / L); 10 is the volume of water dissolved in 1 capsule (mL); 126.904 is the molecular weight of iodine; 166.002 is the molecular weight of potassium iodide.

[0044] To better understand this technical solution, the following embodiments are provided for further explanation:

[0045] Example:

[0046] Experimental Section

[0047] Reagents and Instruments

[0048] Sodium chloride (analytical grade), vitamin C (analytical grade), disodium hydrogen phosphate (analytical grade), glucose (analytical grade), phosphoric acid (analytical grade), methanol (chromatographic grade), acetonitrile (chromatographic grade), Sinopharm Chemical Reagent Co., Ltd.; n-Octylamine (analytical grade), potassium iodide and potassium iodate standard substances, Aladdin Reagent Co., Ltd.; iodine [ 131 I] Sodium hydroxide oral solution, Atomic High-Tech Co., Ltd.; Octadecylsilane-bonded silica gel packed column (4.6 mm × 250 mm × 5 μm), Agilent Technologies, Inc.

[0049] 1260 high performance liquid chromatograph (including quaternary pump, UV detector, column oven and autosampler), Agilent Technologies, USA; LB514 radioactive flow detector, Berthold GmbH, Germany; XPR / 205 0.001 g electronic analytical balance, Mettler Toledo; CRC-55tR activity meter, Capintec Corporation, USA.

[0050] Chromatographic conditions

[0051] An octadecylsilane-bonded silica gel column was used as the packing material. The mobile phase consisted of a 20:1 (V:V) mixture of 5.85 g / L sodium chloride solution (with 0.65 mL of n-octylamine added and pH adjusted to 7.0 with dilute phosphoric acid): acetonitrile. The solution was filtered through a 0.45 μm filter and then ultrasonically removed to remove air bubbles. A radioactive flow detector (BGO detection cell, 150 μL) was connected in series with an ultraviolet detector (detection wavelength of 220 nm). The column temperature was 25 °C, the injection volume was 100 μL, the run time was 12 min, and isocratic elution was performed at a flow rate of 1.5 mL / min.

[0052] Optimization of analytical method run time (iodide content)

[0053] In the study of iodide content, the effect of capsule fillers (antioxidant solution, filler A solution, filler B solution, etc.) on the determination of iodide content was investigated. Water, mobile phase, antioxidant solution, filler A solution, filler B solution, negative control solution, potassium iodate solution, and first control solution were analyzed to determine the appropriate method run time. Figure 1 It can be seen that the elution times of water, mobile phase, antioxidant solution, filler A solution, filler B solution, negative control solution, and potassium iodate solution are all concentrated between 1.0 and 5.5 min. The elution time of iodide in the first control solution is 6.694 min. Therefore, the excipient solution, water, and mobile phase do not interfere with the iodide elution peak. Generally, under isocratic elution conditions, the liquid chromatography run time is usually set to about 1.5 to 2 times the peak retention time. The retention time of the iodide peak is about 6.7 min. Therefore, considering all factors, a run time of 12 min is sufficient for the analysis of iodide content.

[0054] Optimization of injection volume for analytical methods (radiochemical purity)

[0055] Iodine for domestic diagnostic purposes 131 The activity of sodium chloride capsules produced was approximately 650 kBq / capsule. Following the method described in the European Pharmacopoeia, the radioactivity concentration of the sample obtained by diluting the capsules with 10 mL of water was approximately 65 kBq / mL. The chromatogram after sample injection analysis is shown below. Figure 2 As shown. From Figure 2 It can be seen that the response of the main radioactive peak in the test spectrum is low, with a signal-to-noise ratio (S / N) of 18.5, which is greater than 10 and above the limit of quantitation (LOQ). This allows for accurate quantification of the principal component, but the diagnostic use of iodine […]. 131 During the 21-day long-term stability test of sodium chloride capsules, the activity of the capsules after decay was approximately 105 kBq / capsule. The radioactivity concentration of the sample obtained by diluting the capsules with 10 mL of water was approximately 10.5 kBq / mL. The results after sample injection analysis are shown below. Figure 3 As shown. From Figure 3As can be seen, the main peak signal in the measured spectrum is weak and the peak shape is poor, with an S / N ratio of less than 10, which is at the limit of detection (LOD) level. Therefore, accurate quantification is not possible, and this analytical method is no longer applicable.

[0056] Therefore, the injection volume was optimized first. Table 1 shows that when the injection volume was gradually increased from 20 μL to 100 μL, the peak area of ​​the main radioactive peak increased from 192.71 to 657.03. This demonstrates that increasing the injection volume can increase the signal of the main radioactive peak. Generally, the quantitative loop volume of a liquid chromatograph is 100 μL, and a larger injection volume will result in a poorer peak shape. Therefore, the injection volume for this analytical method was selected as 100 μL.

[0057] Table 1. Effect of different injection volumes on the peak area of ​​the main radioactive peak.

[0058]

[0059] Optimization of the preparation method for the first sample solution (radiochemical purity)

[0060] To further improve the response value of the main radioactive peak signal in the capsules and facilitate the detection of potential impurities such as iodate, the capsule sample preparation process was optimized. When the processing concentration of the capsule samples increased from 1 capsule / 10mL, 1 capsule / 8mL, 1 capsule / 6mL, 1 capsule / 4mL, 1 capsule / 2mL to 2 capsules / 2mL, the peak area of ​​the main radioactive peak gradually increased, as shown in Table 2. Due to the large content of filler A in the capsules, as the capsule sample processing concentration increased, the sample solution became more alkaline, and the elution time of the main radioactive peak began to shift earlier, gradually shifting from 6.933 min (1 capsule / 10mL) to 6.039 min (2 capsules / 2mL), exceeding the ±10% range of the elution time of the first control solution in the judgment criteria in section 1.4, and thus failing to meet the requirements for qualitative testing.

[0061] Iodine in diagnostics 131 During the pretreatment of sodium iodide capsules, dilute phosphoric acid is added to adjust the pH of the solution to neutral. This causes the elution time of the main radioactive peak to shift later. At this point, the elution times of the main radioactive peak in the first sample solution and the iodide peak in the first control solution meet the requirements. Therefore, iodine for diagnostic purposes... 131 The pretreatment method for the first sample solution of sodium chloride capsules was determined to be as follows: dissolve the contents of two capsules in 2 mL of 10% phosphoric acid solution. At this time, iodine [ 131 The high signal intensity of the main radioactive peak of iodine ions ensures that iodine [ 131 The accuracy of I] ion elution time and the effective detection of potential radioactive impurities. Under these sample pretreatment conditions, the diagnostic iodine [ 131 During the 21-day long-term stability test of sodium iodide capsules, iodine [ 131I] The main peak signal of radioactive ions is strong and the peak shape is good, such as Figure 3 As shown.

[0062] Table 2. Effect of different sample concentrations on the peak area of ​​the main radioactive peak.

[0063]

[0064]

[0065] Method validation experiment

[0066] System Applicability

[0067] After baseline equilibration of the high-performance liquid chromatograph (HPLC), one injection each of the mobile phase, water, and negative control solution was performed according to the chromatographic conditions. Six injections of the first control solution and one injection of the second control solution were performed. Chromatograms were saved, and the theoretical plate number (n) and tailing factor (T) of iodide in the six injections of the first control solution, as well as the resolution between iodide and iodate in the second control solution, were recorded. The results showed that the negative control solution did not interfere with the iodide peak in the first control solution; the resolution between the iodide and iodate peaks in the second control solution was greater than 2.0, indicating effective separation of iodide and iodate; the theoretical plate number of the iodide peak in the first control solution met the requirement of n ≥ 3500; and the peak area was used as the quantitative parameter for iodide in the first control solution, with T consistently meeting the requirement of ≤ 2. The method demonstrated good system applicability.

[0068] Exclusivity

[0069] iodine [ 131 Potential radioactive impurities were prepared by oxidative degradation of [I] compounds in solution, compared with iodine [ 131 Retention times of the main peak of the compound and the peaks of degradation impurities. From Figure 4 It can be seen that in the radioactive signal, iodine [ 131 The retention time of the iodine peak was 7.090 min, and the retention time of the oxidative degradation product peak was 2.807 min. The resolution between the two was 8.53, which meets the requirement of a resolution of not less than 2.0, and can achieve separation between the degradation product and the main peak iodine. 131 Effective separation of [I] was achieved, with the UV signal showing a peak at 6.758 min for iodide and a peak at 2.501 min for iodate. Based on the UV signal, it was inferred that the potential radioactive impurity obtained from the oxidative degradation was iodine. 131 I] The acid radical, main component and impurities can be effectively separated, and the method has good specificity.

[0070] Linearity and Range

[0071] With a certain concentration of iodine [ 131The iodine [I] solution was used as a linear stock solution and diluted to obtain a series of linear solutions, group a. 665 μL of each linear solution group a was mixed with 335 μL of the carrier solution to obtain linear solutions group b. The resulting radioactive concentrations were 7.696 KBq / mL, 15.392 KBq / mL, 76.960 KBq / mL, 153.920 KBq / mL, and 575.350 KBq / mL, respectively. The relationship between the peak area and the radioactive concentration was investigated, and the linear range was determined. The peak area was compared with that of iodine [I] 131 Linear regression was performed on the radioactivity concentration of the substance, and the linear curve is shown in... Figure 5 .from Figure 5 It can be seen that within the radioactive concentration range of 7.696–575.350 KBq / mL, the linear equation is y = 20.461x - 14.415, with a correlation coefficient r = 1.000, which meets the requirement of a correlation coefficient r ≥ 0.990, indicating that the method has good linearity and range.

[0072] LOD and LOQ

[0073] The S / N method is used to determine LOD and LOQ. The S / N of LOD should be ≥3, and the S / N of LOQ should be ≥10. The S / N of the radioactive concentration in the linear solution group b is used to infer the iodine concentration. 131 The appropriate concentrations of LOD and LOQ in the iodine solution were determined, and then the radioactive concentrations at the LOD and LOQ levels were detected and analyzed to obtain the iodine [ 131 The detection limit for the I] compound solution is 1.517 KBq / mL, corresponding to an S / N ratio that meets the requirement of ≥3, as shown in Table 3; iodine [ 131 The limit of quantitation for the I] compound solution is 5.106 KBq / mL, and the corresponding S / N meets the requirement of ≥10, as shown in Table 4.

[0074] Table 3 shows the experimental results of LOD.

[0075]

[0076] Table 4 shows the experimental results of LOQ.

[0077]

[0078] Accuracy

[0079] According to the diagnosis, iodine [ 131 The formula composition of sodium chloride capsules is as follows: [I] iodine-free [ 131 I] blank excipients (equal amounts of antioxidant, filler A, and filler B) were placed in a 10 mL vial, and 2960 KBq / mL iodine was accurately measured. 131 Add 150 μL of sodium chloride oral solution and let stand for 10 minutes to allow the iodine in the solution to […]. 131The iodine [I] compound was fully adsorbed onto the solid. 2 mL of 10% dilute phosphoric acid was accurately added to dissolve it. After standing, the supernatant was collected and filtered through a 0.2 μm filter membrane. 665 μL of the filtrate was mixed thoroughly with 335 μL of the carrier solution to prepare six aliquots for accuracy determination. Chromatographic analysis was performed on these aliquots, and the iodine [I] compound was recorded. 131 Substituting the peak area of ​​the main radioactive peak of iodine into the linear regression equation, we can calculate the iodine [ 131 The measured values ​​of radioactive concentration of iodine [I] compounds. Table 6 shows the values ​​of iodine [I] in the solutions used for accuracy determination. 131 The average recovery rate of the I] compounds was 80.90%, and the relative standard deviation (RSD) was 0.67%, which meets the recovery rate requirement (70%–125%).

[0080] Table 6. Experimental results of accuracy determination

[0081]

[0082]

[0083] stability

[0084] Prepare a second control solution and a test solution. Inject the second control solution and the test solution at 0h, 6h, 24h, and 48h according to the chromatographic conditions, and record the chromatograms. As shown in Table 7, no new impurity peaks were generated in the second control solution and the test solution within 48h; iodine […] at different time points. 131 The RSD of the ratio (in percentage) of the radiochemical purity of the main peak of iodine to that at 0 h was 0.23%, satisfying the condition RSD ≤ 2.0%; iodine at different time points [ 131 The RSD of the ratio of the peak area of ​​the main peak of the I] compound to the peak area of ​​the main peak at 0h (in percentage terms) was 0.79%, which satisfies RSD≤2.0%, indicating that the stability of the second control solution and the test solution is good.

[0085] Table 7. Experimental results of stability determination

[0086]

[0087] Durability

[0088] The effects of chromatographic conditions, including column temperature, flow rate, and mobile phase pH, on the determination results were investigated using the second control solution and the test solution. The results are shown in Tables 8 and 9. Table 8 shows that under each chromatographic condition, the concentration of iodine in the test solution […]. 131 I] compound peaks and iodine [ 131 The resolution of the acid radical peaks was greater than 2.0; calculated as an area percentage, the iodine concentration in the test solution was […]. 131The RSD of the radiochemically pure iodide was 0.14%, meeting the requirement of RSD ≤ 2.0%. Table 9 shows that the retention time of iodide in the second control solution was related to the iodine content in the test solution. 131 The RSD of the retention time ratio of iodate in the second control solution was 0.74%, which meets the requirement of RSD ≤ 2.0%; the retention time of the iodate peak in the second control solution was similar to that in the test solution. 131 The RSD of the retention time ratio of the acid radical peak was 0.47%, which meets the requirement of RSD≤2.0%, indicating that the method has good robustness.

[0089] Table 8. Experimental results of durability testing (1)

[0090]

[0091] Note: 1) The flow rate is 1.5 mL / min, and the pH of the mobile phase is 7.0;

[0092] 2) Column temperature: 25℃; Mobile phase pH: 7.0;

[0093] 3) Column temperature: 25℃, flow rate: 1.5 mL / min

[0094] Table 9 Durability test results (2)

[0095]

[0096] Note: 1) The flow rate is 1.5 mL / min, and the pH of the mobile phase is 7.0;

[0097] 2) Column temperature: 25℃; Mobile phase pH: 7.0;

[0098] 3) Column temperature: 25℃, flow rate: 1.5 mL / min

[0099] Precision

[0100] After the high-performance liquid chromatography (HPLC) baseline was equilibrated, an experimenter injected one sample into each of the six test solutions according to the chromatographic conditions and recorded the chromatograms. The iodine content in the six test solutions was […]. 131 The RSD of the radiochemically pure iodine peak of the I] compound was 0.17%, meeting the requirement of RSD ≤ 2.0%, indicating good reproducibility of the method. Two researchers injected one injection into each of the six test solutions according to the chromatographic conditions in 1.2 and recorded the chromatograms. Iodine […] was present in the 12 test solutions. 131 The RSD of the radioactive main peak of the I] compound was 0.16%, which meets the requirement of RSD≤2.0%, indicating good intermediate precision of the method.

[0101] Determination of radiochemical purity and iodide content in samples

[0102] Three batches of diagnostic iodine were tested respectively.131 The radiochemical purity and iodide content in sodium iodide capsules were determined according to the preparation methods of the first and second sample solutions, and the determination was performed under chromatographic conditions. The iodide content was calculated using the external standard method, and the radiochemical purity was calculated using the area normalization method (%). The results are shown in Table 10. From Table 10, it can be seen that: 3 batches of diagnostic iodine... 131 The iodide content in sodium iodide capsules was less than 20 μg / capsule in all three batches of diagnostic iodine [I] capsules. 131 The radiochemical purity of sodium chloride capsules is higher than 95%.

[0103] Table 10 Experimental results of radiochemical purity and iodide content in samples.

[0104]

[0105] Experimental conclusions

[0106] Through the use of iodine for diagnosis [ 131 A study was conducted on the pretreatment method, injection volume, and sample analysis time of sodium iodide capsules, establishing a method for determining diagnostic iodine […]. 131 High-performance liquid chromatography (HPLC) method for determining the radiochemical purity and iodide content of sodium iodide capsules. After thorough validation, the HPLC method for determining diagnostic iodine […]. 131 The system suitability, accuracy, precision (repeatability, intermediate precision), linearity and range, limit of detection and limit of quantitation, specificity, stability, and robustness of sodium iodide capsules for radiochemical purity and iodide content all meet the validation requirements. In summary, high-performance liquid chromatography (HPLC) can be used to determine diagnostic iodine […]. 131 The method for measuring the chemical purity and iodide content of sodium chloride capsules lays a solid foundation for improving quality control by benchmarking against international standards.

[0107] The above-disclosed embodiments are merely preferred examples of the HPLC method for determining the radiochemical purity and iodine content of sodium iodide capsules for diagnostic purposes according to the present invention. Of course, they should not be construed as limiting the scope of the present invention. Those skilled in the art can understand that implementing all or part of the above-described embodiments and making equivalent changes in accordance with the claims of the present invention are still within the scope of the invention.

Claims

1. HPLC method for determining the radiochemical purity and iodine content of sodium iodide capsules for diagnostic purposes. Its features include the following steps; Set chromatographic conditions and connect a radioactive flow detector and an ultraviolet detector in series; Prepare disodium hydrogen phosphate solution, glucose solution, vitamin C solution, first control solution, potassium iodate solution, second control solution, carrier solution, first sample solution, second sample solution, negative control solution and test solution; Based on the chromatographic conditions and judgment criteria, the radiochemical purity and iodide content of the first sample solution and the second sample solution were determined in three batches.

2. The HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules as described in claim 1. Its characteristics are: The chromatographic conditions include using an octadecylsilane-bonded silica gel column as the packing material, a mobile phase of a 20:1 mixture of 5.85 g / L sodium chloride solution and acetonitrile, and ultrasonic removal of air bubbles after filtration through a 0.45 μm filter membrane.

3. The HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules as described in claim 1, characterized in that; The chromatographic conditions also include a column temperature of 25°C, an injection volume of 100 μL, a run time of 12 min, and isocratic elution at a flow rate of 1.5 mL / min.

4. The HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules as described in claim 1, characterized in that... ； The criteria for determination include that, in the radiochromatogram of the first sample solution, the radiochemical purity calculated by the normalization method of radioactive peak area should not be less than 95%, and the retention time of the main radioactive peak should not differ from the retention time of the iodide peak in the first control solution by more than ±10%.

5. The HPLC method for determining the radiochemical purity and iodine content of diagnostic sodium iodide capsules as described in claim 1, characterized in that... ； The judgment criteria also include that in the ultraviolet chromatogram of the second sample solution, in the chromatogram of the negative control solution, all peaks must not have a retention time similar to that of the iodide ion peak in the first control solution. In the chromatogram of the second control solution, the resolution between the iodide ion peak and the iodate ion peak should not be less than 2 and should not exceed the peak area corresponding to the iodide in the chromatogram of the first control solution, i.e., the iodide ion content should be ≤20μg / particle.

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