A method for determining the radiochemical purity of 99mTc-MDP injection solution

Abstract

This invention relates to the field of radiochemical purity analysis, and more particularly to a method for determining... 99m A method for determining the radiochemical purity of Tc-MDP injection. This method includes using thin-layer chromatography to determine... 99m The radiochemical purity of Tc-MDP injection solution was determined, with polyamide thin-layer chromatography as the stationary phase and sodium acetate and hydrochloric acid as the developing solvent. This method can simultaneously […]. 99m Tc-MDP injection effectively separates the product from impurities, exhibiting good specificity, accuracy, stability, and reliability, and can be used for... 99m Determination, control and precise detection of radiochemical purity in Tc-MDP injection solution.

Description

Technical Field

[0001] This invention relates to the field of radiochemical purity analysis, and particularly to a method for determining technetium […]. 99m Tc] Methylene diphosphonate injection (abbreviated as Tc) 99m Methods for radiochemical purity of Tc-MDP injection. Background Technology

[0002] 99m Tc-MDP injection is an ideal bone imaging agent used for the early diagnosis of malignant metastatic bone tumors and primary bone tumors. It is also of great value in monitoring the survival of transplanted bone, diagnosing traumatic fractures, bone inflammation, and metabolic bone diseases.

[0003] Radiochemical purity is 99m One of the efficacy control indicators for Tc-MDP injection is its level, which determines the clinical diagnostic effect. The main factor affecting the radiochemical purity is the content of radiochemical impurities. The component analysis of the raw material used to prepare this product, stannous methylene diphosphonate for injection (MDP cartridge), plays a crucial role in impurity research. Its general composition includes methylene diphosphonic acid, reducing agents (stannous chloride / stannous fluoride, etc.), antioxidants (ascorbic acid, etc.), and pH adjusters. The labeling principle of this product is: high technetium […]. 99m [Tc] salt is reduced from the VII to IV oxidation state by stannous chloride, and undergoes a complexation reaction with excess methylene diphosphonic acid. The mixture is allowed to stand at room temperature for a certain period to ensure the complexation reaction proceeds fully. In the labeling process, when the reducing agent is insufficient, high-technetium [ 99m If the Tc salt cannot be completely reduced, the possible radioactive chemical impurity is free technetium. 99m [Tc] salts, high levels of which can increase blood background levels and can cause imaging of the thyroid gland and gastric mucosa; under sufficient reducing agent conditions, high technetium [ 99m If the [Tc] salt is reduced but not completely complexed with methylene diphosphonic acid, then a radioactive chemical impurity such as reduced hydrolyzed technetium may be present. 99m Tc] (hereinafter referred to as colloidal technetium) 99m Tc]) can be distributed in the liver cortex.

[0004] The presence of radioactive chemical impurities affects the in vivo distribution and metabolism of drugs. To ensure the diagnostic effectiveness of this product and the safety of patient use, strict control over its main radioactive chemical impurity, technetium, is necessary. 99m Tc] salts and colloidal technetium [ 99m These two impurities, Tc, are controlled. Therefore, the established radiochemical purity analysis method should have good specificity and accuracy.

[0005] for 99mThe radiochemical purity control of Tc-MDP injection is performed using a two-system analytical method according to the Chinese Pharmacopoeia 2020 (ChP2020), the United States Pharmacopeia 42-NF37 (USP42-NF37), and the European Pharmacopoeia 10.1 (EP10.1). In EP10.1, ITLC-SG chromatography paper is used as the stationary phase, and 136 g / L sodium acetate solution and 2-butanone are used as the developing solvents for system one and system two, respectively. ChP2020 and USP42-NF37 both use paper chromatography, with 0.9% sodium chloride solution and 85% methanol as the developing solvents for system one and system two, respectively.

[0006] Both ChP2020 and USP42-NF37 use paper chromatography, with 0.9% sodium chloride solution and 85% methanol as the developing solvents for System 1 and System 2, respectively. System 1 requires nitrogen purging, which makes the separation process time-consuming and cumbersome, and is not conducive to the rapid release of products. Summary of the Invention

[0007] To solve the above-mentioned technical problems, the present invention provides a method for measuring... 99m Methods for radiochemical purity of Tc-MDP injection solution.

[0008] This invention provides a method for determining the radiochemical purity of 99mTc-MDP injection solution, using thin-layer chromatography. 99m The Tc-MDP injection solution has radiochemical purity, wherein the stationary phase is a polyamide thin-layer plate, and the developing solvent is sodium acetate and hydrochloric acid.

[0009] In this invention, in response to the prior art... 99m The shortcomings of the analytical method for the radiochemical purity of Tc-MDP injection are mainly addressed by simplifying the determination of radiochemical purity through the use of optimized stationary phase and developing solvent. 99m The analytical method for determining the radiochemical purity of Tc-MDP injection solution provided by this invention 99m Thin-layer chromatography (TLC) methods for radiochemical purity determination of Tc-MDP injection offer better specificity, accuracy, stability, and reliability, and can be used for... 99m Determination and quality control of radiochemical purity of Tc-MDP injection solution.

[0010] Preferably, the concentration of sodium acetate is 0.5–2.0 mol / L.

[0011] Preferably, the concentration of the hydrochloric acid is 0.08–0.12 mol / L.

[0012] More preferably, the developing agent is sodium acetate and hydrochloric acid in a volume ratio of 0.8:1 to 1.2:1.

[0013] Preferably, the stationary phase is a polyamide thin-film plate with a size of 1×12.5cm.

[0014] This invention provides a method for thin-layer chromatography to... 99m The analytical method for the radiochemical purity of Tc-MDP injection solution, when using thin-layer chromatography, commonly uses silica gel plates, silicate plates, or chromatography paper as the stationary phase, and organic solvents such as methanol, acetonitrile, acetone, and dichloromethane as the mobile phase. However, due to... 99m The main component of Tc-MDP injection has a complex structure. Under conventional analytical conditions, it is difficult to effectively separate the main component and the two impurities. Even when separated, the main component may exhibit severe tailing or poor peak shape, leading to large and unstable detection results. Through extensive experimentation, this invention utilizes a polyamide thin-layer plate as the stationary phase and sodium acetate and hydrochloric acid of specific concentrations and ratios as the developing solvent. This single-system approach effectively separates the main component and the two impurities, significantly shortening the analytical time. 99m The analysis time for the radiochemical purity of Tc-MDP injection is short, and the peak shape of the main component is good without tailing. The two impurities will not interfere with the analysis of the radiochemical purity of the main component.

[0015] Further optimization also includes preparing the test solution according to high technetium [ 99m To determine the concentration of sodium stannous methylene diphosphonate injection, inject 4–6 mL into a lyophilized vial of stannous methylene diphosphonate, mix and dissolve, and allow to stand to obtain the desired solution. 99m Tc-MDP injection.

[0016] Further optimization includes preparing a reference solution by adding 1–3 mL of technetium containing 100 MBq–400 MBq to the MDP standard kit. 99m Sodium tcoate injection, let stand.

[0017] Further preferably, it also includes preparing test solution 1 and test solution 2; the test solution 1 is obtained by eluting the molybdenum technetium generator with sodium chloride elution solution to obtain high technetium [ 99m Tc] sodium acid solution; the test solution 2 is prepared by adding high technetium [Tc] to SnCl2·2H2O in a vial. 99m Sodium thiocyanate injection solution, mix and let stand.

[0018] Further optimization includes taking the test solution, reference solution, test solution 1, and test solution 2, spotting them at the origin of one end of the polyamide thin-layer plate, drying them, placing the paper strip into a container containing the developing agent, and developing it until it reaches the solvent front. Then, the paper strip is removed, dried, and measured.

[0019] Further optimization is achieved by setting the development temperature to 10–30°C.

[0020] Further preferred, the determination99m Methods for determining the radiochemical purity of Tc-MDP injection include:

[0021] A) Preparation of test solution 1: Elute the molybdenum-technetium generator with sodium chloride elution solution to obtain high technetium [ 99m Tc] sodium acid solution;

[0022] B) Preparation of test solution 2: Weigh 8-10 mg of SnCl2·2H2O into a vial, add 0.08-0.1 mL of technetium [ 99m Sodium tcate injection solution, shake well and let stand;

[0023] C) Preparation of reference solution: Add 1–2 mL of technetium containing 100 MBq–400 MBq to the MDP standard kit. 99m Sodium tcate injection, let stand;

[0024] D) Preparation of the test solution: According to the high-technetium [ 99m To determine the concentration of sodium stannous dimethyl disulfide injection, inject 4–6 mL into a vial of lyophilized stannous dimethyl disulfide, shake to dissolve the lyophilized product, and allow to stand. 99m Tc-MDP injection;

[0025] E) Determination: Take the test solution, reference solution, test solution 1, and test solution 2, and spot them at the origin of one end of the polyamide thin-layer plate. After drying, place the paper strip into a container containing the developing agent and develop it. When it reaches the solvent front, remove the paper strip, let it dry, and then perform the determination.

[0026] As one specific embodiment of the present invention, the measurement 99m The method for determining the radiochemical purity of Tc-MDP injection solution includes the following steps:

[0027] A) Prepare test solution 1 (impurity 1: technetium [...]) 99m Tc] sodium acid solution)

[0028] The molybdenum technetium generator is obtained by rinsing it with sodium chloride solution.

[0029] B) Prepare test solution 2 (impurity 2 colloidal technetium) 99m Tc])

[0030] Accurately weigh 10 mg of SnCl2·2H2O into a vial, add 0.1 mL of technetium [ 99m Sodium Tcate injection, shake well, and let stand for about 15 minutes to react;

[0031] C) Preparation of reference solution

[0032] Add 2 mL of technetium containing 100 MBq to 400 MBq to one bottle of MDP standard reagent kit. 99mSodium tcate injection, let stand for 15 minutes;

[0033] D) Preparation of the test solution ( 99m Tc-MDP injection)

[0034] According to Gao De [ 99m To determine the concentration of sodium stannous dimethyl disulfide injection, take 4-6 mL and inject it into a bottle containing lyophilized stannous dimethyl disulfide. Shake thoroughly to ensure complete dissolution of the lyophilized product, and let it stand for at least 5 minutes.

[0035] E) Determination Method

[0036] Using a glass capillary tube or microsyringe, take appropriate amounts of the test solution, reference solution, test solution 1, and test solution 2, and spot them at the origin at one end of a polyamide thin-layer plate (1×12.5cm). Allow the plate to dry. Place the paper strip into a chromatography tank containing the developing solvent and develop. When the solvent front reaches 10cm, remove the paper strip, allow it to dry, and place it on a radiometric thin-layer scanner for scanning. Measure the spectrum and data, and calculate the R0. f Value and radiochemical purity, and according to R f Choose appropriate conditions for the value and separation status.

[0037] The beneficial effects of the present invention are at least as follows: the detection method provided by the present invention can simultaneously […]. 99m The main component and two impurities in Tc-MDP injection were separated, demonstrating rapid analysis speed, a resolution greater than 1.5, good peak shape of the main component without tailing, and no interference from the two impurities in the analysis of the radiochemical purity of the main component. Methodological validation for linearity, specificity, precision, and robustness was conducted according to the 2020 edition of the Chinese Pharmacopoeia's "9101 Analytical Method Validation Guidelines," proving that this method has good accuracy, stability, and reliability, and can be used for... 99m Determination and control of the radiochemical purity of Tc-MDP injection solution. The establishment of this analytical method enables the determination and control of the radiochemical purity of Tc-MDP injection solution. 99m Precise detection of radiochemical purity in Tc-MDP injection solution. Attached Figure Description

[0038] To more clearly illustrate the technical solutions in this 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 some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0039] Figure 1 This is a chromatogram of the test solution in an embodiment of the present invention;

[0040] Figure 2 The reference solution chromatogram is shown in the embodiment of the present invention.

[0041] Figure 3 This is the chromatogram of test solution 1 in an embodiment of the present invention;

[0042] Figure 4 The chromatogram of test solution 2 in this embodiment of the invention;

[0043] Figure 5 The chromatograms for the linearity and range of the test solution in this embodiment of the invention are shown below.

[0044] Figure 6 This is the chromatogram of the test solution of Comparative Example 1 of the present invention. Detailed Implementation

[0045] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0046] Example 1

[0047] This embodiment provides a thin-layer chromatography method for the determination of technetium. 99m The method for determining the radiochemical purity of Tcq methylene bisphosphonate injection includes the following steps:

[0048] A) Prepare test solution 1 (impurity 1: technetium [...]) 99m Tc] sodium acid solution)

[0049] The molybdenum technetium generator is obtained by rinsing it with sodium chloride solution.

[0050] B) Prepare test solution 2 (impurity 2 colloidal technetium) 99m Tc])

[0051] Accurately weigh 10 mg of SnCl2·2H2O into a vial, add 0.1 mL of technetium [ 99m Sodium Tcate injection, shake well, and let stand for about 15 minutes to react;

[0052] C) Preparation of reference solution

[0053] Add 2 mL of technetium containing 200 MBq to one bottle of MDP standard reagent kit. 99m Sodium tcate injection, let stand for 15 minutes;

[0054] D) Preparation of the test solution ( 99m Tc-MDP injection)

[0055] According to Gao De [99m To determine the concentration of sodium stannous dimethyl disulfide injection, take 5 mL and inject it into a bottle containing stannous dimethyl disulfide lyophilized product. Shake thoroughly to ensure complete dissolution of the lyophilized product, and let stand for 10 minutes.

[0056] E) Determination Method

[0057] Using a glass capillary tube or microsyringe, take appropriate amounts of the test solution, reference solution, test solution 1, and test solution 2, and spot them at the origin at one end of a polyamide thin-layer plate (1×12.5cm). Allow the plate to dry. Place the paper strip into a chromatography tank containing the developing solvent and develop at 25℃. When the solvent front reaches 10cm, remove the paper strip, allow it to dry, and place it on a radiometric thin-layer scanner for scanning. Measure the spectrum and data, and calculate the R0. f Value and radiochemical purity.

[0058] in:

[0059] Stationary phase: Polyamide thin-film (1×12.5cm);

[0060] Developing solvent: 1 mol / L sodium acetate : 0.1 mol / L hydrochloric acid = 1:1 (V / V)

[0061] Instruments, reagents, and consumables:

[0062] Instrument: AR-2000 radiometric thin-layer scanner (BIOSCAN, USA);

[0063] CLIMACELL222EVO stability test chamber (MMM Group Munich Medical Machinery Co., Ltd.); XPR205 / A electronic balance (Mettler-Toledo International Trading (Shanghai) Co., Ltd.); CRC-15W activity meter.

[0064] Reagents: Sodium chloride injection (Shijiazhuang No. 4 Pharmaceutical Co., Ltd.); Sodium acetate, concentrated hydrochloric acid, anhydrous stannous chloride (analytical grade, Sinopharm Chemical Reagent Co., Ltd.); Water (self-made double-distilled water).

[0065] Consumables: Polyamide thin-layer plates (Luqiao Sijia Biochemical Plastics Factory, Taizhou City, Zhejiang Province); chromatography tanks; glass capillaries or microsyringes.

[0066] Standard reagent kit: MDP standard kit (POLATOM, Poland).

[0067] Efficacy validation: The methods described in the examples were validated for specificity, linearity, precision, and robustness in accordance with the "Guidelines for Validation of Analytical Methods 9101" in the 2020 edition of the Chinese Pharmacopoeia, as detailed below:

[0068] The specific preparation process of each solution in Example 1, as well as the experimental verification process and results of the method of the present invention, are shown in Examples 1 to 4.

[0069] Example 1: Specificity Test

[0070] Test solution 1 (Impurity 1, high technetium) 99m [Tc] sodium chloride solution: obtained by rinsing the molybdenum technetium generator with sodium chloride rinsing solution.

[0071] Test solution 2 (impurity 2 colloidal technetium) 99m Tc]): Accurately weigh 10 mg of SnCl2·2H2O into a vial, add 0.1 mL of technetium [ 99m Sodium thiocyanate injection solution, shake well, and let stand for about 15 minutes to react.

[0072] Reference solution: Add 2 mL of technetium containing 200 MBq to one bottle of MDP standard kit. 99m Sodium tcoate injection, let stand for 15 minutes.

[0073] Test solution ( 99m Tc-MDP injection): according to technetium [ 99m To determine the concentration of sodium stannous dimethyl disulfide injection, take 5 mL and inject it into a bottle containing stannous dimethyl disulfide lyophilized product. Shake thoroughly to ensure complete dissolution of the lyophilized product, and let stand for 15 minutes.

[0074] Using a glass capillary tube or microsyringe, take appropriate amounts of the test solution, reference solution, test solution 1, and test solution 2, and spot them at the origin at one end of a polyamide thin-layer plate (1×12.5cm). Allow the plate to dry. Place the paper strip in a chromatography tank containing 1.0mol / L sodium acetate:0.1mol / L hydrochloric acid = 1:1 (v / v) and develop at 25℃. When the solvent front reaches 10cm, remove the paper strip, allow it to dry, and scan it using a radiometric thin-layer scanner to obtain the chromatograms and data. The results are shown in Tables 1-2, and the chromatogram of the test solution is shown in [Table 1-2]. Figure 1 See the chromatogram of the reference solution. Figure 2 The chromatogram of test solution 1 is shown in [reference needed]. Figure 3 The chromatogram of test solution 2 is shown in [reference needed]. Figure 4 .

[0075] Table 1. R values ​​for the reference solution, test solution 1, and test solution 2 of the test sample solution. f value

[0076]

[0077] Table 2 Calculation of Separation Results

[0078]

[0079] The formula for calculating resolution (R) is:

[0080] R = 2 × (d2 - d1) / (W1 + W2)

[0081] In the formula:

[0082] d2 is the distance between the latter of two adjacent peaks and the origin;

[0083] d1 is the distance between the first of two adjacent peaks and the origin;

[0084] W1 and W2 are the peak widths of two adjacent peaks.

[0085] Conclusion: Technetium [ 99m Tc] Methylene diphosphonate injection R f The value is consistent with the main peak of the reference solution, approximately 1.0; the R values ​​for pertechnetate and colloidal technetium are... f The value is approximately 0. The separation degrees between the main peak and the impurity peak are 1.74 and 1.78, respectively, which meet the requirement of R>1.0, proving that technetium [ 99m Tc]methylene diphosphonate can be effectively separated from the two impurities, and the main component has a good peak shape without tailing. The two impurities will not interfere with the analysis of the radiochemical purity of the main component.

[0086] Experiment Example 2: Linearity and Range Test

[0087] Technetium of different activities was taken using a microsyringe. 99m Tc]methylene bisphosphonate injection sample was spotted, and its total radioactivity count was recorded. The relationship between radioactivity and total radioactivity count was investigated within a certain range of radioactivity. [The text then abruptly shifts to a seemingly unrelated topic:] ...using technetium[... 99m The radioactivity of Tc]methylene bisphosphonate injection was plotted on the x-axis, and the total radioactivity count on the y-axis, using a linear regression equation. The results are shown in Table 3, and the chromatograms for linearity and range are shown below. Figure 5 .

[0088] Table 3 Linearity and Range

[0089]

[0090] Conclusion: When the measured technetium [ 99m When the radioactivity of Tc]methylene bisphosphonate injection is in the range of 0.027 μCi to 42.4 μCi, the radioactivity count of the sample is linearly related to the radioactivity, with the linear equation being y = 8791.45115x + 4579.04187 and the correlation coefficient r = 0.997, which meets the requirement of r ≥ 0.990, indicating a good linear relationship.

[0091] Experimental Example 3 Precision

[0092] Repeatability: Using a glass capillary tube or microsyringe, take an appropriate amount of the test solution and spot it at the origin of one end of a polyamide thin-layer plate (1×12.5cm). Spot the sample six times in parallel, let it dry, and then place the paper strip into a developing tank containing 1.0mol / L sodium acetate:0.1mol / L hydrochloric acid = 1:1 (v / v). The developing temperature is 25℃. When the solvent front reaches 10cm, remove the paper strip, let it dry, and then scan it on a radiochromatographic scanner to obtain the spectrum and data. The results are shown in Table 4.

[0093] Table 4 Repeatability Results

[0094]

[0095]

[0096] Intermediate precision: Another analyst used a glass capillary or microsyringe to take an appropriate amount of the test solution and spot it at the origin of one end of a polyamide thin-layer plate (1×12.5cm). Two operators each spotted the sample 6 times in parallel. After drying, the paper strip was placed in a developing tank containing 1.0mol / L sodium acetate:0.1mol / L hydrochloric acid = 1:1 (v / v) for development. When the development reached 10cm from the solvent front, the paper strip was removed, dried, and scanned on a radiochromatographic scanner to obtain the spectrum and data. The results are shown in Table 5.

[0097] Table 5 Intermediate Precision Results

[0098]

[0099] Conclusion: Based on the results of 6 repeatability tests, the main peak R... f The value was approximately 1.0, the radiochemical purity was ≥90%, and the RSD of the radiochemical purity determination results was ≤2.0%. The intermediate precision was based on 12 tests conducted by two individuals, with the main peak R... f The value is approximately 1.0, the radiochemical purity is ≥90%, and the RSD of the radiochemical purity determination result is ≤2.0%.

[0100] Experiment Example 4 Durability Test

[0101] Take an appropriate amount of the test solution using a glass capillary tube or microsyringe and spot it at the origin of one end of a polyamide thin-layer plate (1×12.5cm). Spot the sample parallel to the origin, let it dry, and develop the paper strip under the following conditions: ① Developing solvent ratio: 1mol / L sodium acetate : 0.1mol / L hydrochloric acid solution = 0.8:1 (V / V), 0.9:1 (V / V), 1.0:1 (V / V), 1.1:1 (V / V), 1.2:1 (V / V); ② Change the developing temperature: 10℃, 25℃, 30℃; ③ Use polyamide thin-layer plates from different batches of the same manufacturer. When the development reaches 10cm from the solvent front, remove the paper strip, let it dry, and scan it on a radiochromatographic scanner to obtain the spectrum and data. The results are shown in Table 6.

[0102] Table 6 Durability Test Results

[0103]

[0104]

[0105] The results of the determination of polyamide thin-layer plates and sheets from different batches of the same manufacturer under various conditions were as follows: the ratio of 1 mol / L sodium acetate solution to 0.1 mol / L hydrochloric acid solution varied from 0.8:1 (V / V) to 1.2:1 (V / V); the temperature ranged from 10℃ to 30℃; and the ratio of 1 mol / L sodium acetate solution to 0.1 mol / L hydrochloric acid solution varied from 0.8:1 (V / V) to 1.2:1 (V / V). 99m Tc] Methylene diphosphonate main peak R f At a value of approximately 1.0, the radiochemical purity RSD is 0.58%, which meets the requirement of RSD≤2.0%.

[0106] Comparative Example 1

[0107] Using a glass capillary tube or microsyringe, take appropriate amounts of the sample solution, test solution 1, and test solution 2, and spot them at the origin on one end of a silica gel plate or silicate plate (1×12.5cm). Allow them to dry. Place the paper strip in a chromatography tank containing 1.0mol / L sodium acetate:0.1mol / L hydrochloric acid = 1:1 (v / v) and develop it at 25℃. When the solvent front reaches 10cm, remove the paper strip, allow it to dry, and scan it on a radiometric thin-layer scanner. The main component and the two impurities are not visible in the obtained spectrum. (Comparative Example 2)

[0108] Take an appropriate amount of the test solution using a glass capillary tube or microsyringe and spot it at the origin at one end of a polyamide thin-layer plate (1×12.5cm). Allow it to dry. Place the paper strip in a chromatography tank containing 0.9% sodium chloride injection solution and develop it at 25℃. When the solvent front reaches 10cm, remove the paper strip, allow it to dry, and scan it using a radiometric thin-layer scanner. The obtained spectrum and data show severe tailing of the main component. See the results below. Figure 6 .

[0109] Comparative Example 3

[0110] Take an appropriate amount of the test solution using a glass capillary tube or microsyringe and spot it at the origin of one end of a polyamide thin-layer plate (1×12.5cm). Let it dry, then place the paper strip into a chromatography tank containing acetonitrile and develop it. When the solvent front reaches 10cm, remove the paper strip, let it dry, and place it on a radiometric thin-layer scanner to scan it. The obtained spectrum and data show that the main component in the obtained spectrum has very severe tailing, and the main component and the two impurities cannot be effectively separated.

[0111] The detection method provided by this invention can simultaneously detect technetium [ 99m This method effectively separates the main component and impurities in Tc]methylene bisphosphonate injection and solves the problem of main peak tailing. It exhibits good specificity, accuracy, stability, and reliability, and can be used for technetium […]. 99m The determination and control of radiochemical purity in Tc]methylene bisphosphonate injection. Simultaneously, the establishment of this analytical method enables the determination and control of the radiochemical purity of technetium […]. 99m Precise detection of radiochemical purity in Tcq methylene bisphosphonate injection.

[0112] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method of measurement 99m A method for determining the radiochemical purity of Tc-MDP injection solution, characterized in that... Determination by thin-layer chromatography 99m The Tc-MDP injection solution has radiochemical purity, wherein the stationary phase is a polyamide thin-layer plate, and the developing agent is sodium acetate and hydrochloric acid with a volume ratio of 0.8:1 to 1.2:

1. The concentration of sodium acetate is 0.5~2.0 mol / L; The concentration of the hydrochloric acid is 0.08~0.12 mol / L; It also includes preparing the test solution, according to high technetium [ 99m To determine the concentration of sodium stannous methylene diphosphonate injection, inject 4-6 mL into a lyophilized vial of stannous methylene diphosphonate, mix and dissolve, and allow to stand to obtain the desired solution. 99m Tc-MDP injection.

2. The determination according to claim 1 99m A method for determining the radiochemical purity of Tc-MDP injection solution, characterized in that... The stationary phase is a polyamide thin-film plate with a size of 1×12.5 cm.

3. The determination according to claim 1 or 2 99m A method for determining the radiochemical purity of Tc-MDP injection solution, characterized in that... This also includes preparing a reference solution by adding 1–3 mL of technetium containing 100–400 MBq to the MDP standard kit. 99m Sodium tcoate injection, let stand.

4. The determination according to claim 3 99m A method for determining the radiochemical purity of Tc-MDP injection solution, characterized in that... It also includes preparing test solution 1 and test solution 2; the test solution 1 is obtained by eluting the molybdenum technetium generator with sodium chloride elution solution to obtain high technetium [ 99m Tc] sodium acid solution; the test solution 2 is prepared by adding high technetium [Tc] to SnCl2·2H2O in a vial. 99m Sodium thiocyanate injection solution, mix and let stand.

5. The determination according to claim 4 99m A method for determining the radiochemical purity of Tc-MDP injection solution, characterized in that... The method also includes taking the test solution, reference solution, test solution 1, and test solution 2, spotting them at the origin of one end of the polyamide thin-layer plate, drying them, placing the paper strip into a container containing the developing agent, and developing it until it reaches the solvent front. Then, the paper strip is removed, dried, and measured.

6. The determination according to claim 5 99m A method for determining the radiochemical purity of Tc-MDP injection solution, characterized in that... The unfolding temperature is 10~30℃.

7. The determination according to claim 6 99m A method for determining the radiochemical purity of Tc-MDP injection solution, characterized in that... include: A) Preparation of test solution 1: Elute the molybdenum-technetium generator with sodium chloride elution solution to obtain high technetium [ 99m Tc] sodium acid solution; B) Preparation of test solution 2: Weigh 8-10 mg of SnCl2·2H2O into a vial, add 0.08-0.1 mL of technetium [ 99m Sodium tcate injection solution, shake well and let stand; C) Preparation of reference solution: Add 1-2 mL of technetium containing 100 MBq-400 MBq to the MDP standard kit. 99m Sodium tcate injection, let stand; D) Preparation of the test solution: According to the high-technetium [ 99m To determine the concentration of sodium stannous dimethyl disulfide injection, inject 4-6 mL into a vial of lyophilized stannous dimethyl disulfide, shake to dissolve the lyophilized product, and allow to stand. 99m Tc-MDP injection; E) Determination: Take the test solution, reference solution, test solution 1, and test solution 2, and spot them at the origin of one end of the polyamide thin-layer plate. After drying, place the paper strip into a container containing the developing agent and develop it. When it reaches the solvent front, remove the paper strip and let it dry before performing the determination.

Images