CN115015441A - Determination of lutetium [ Lu ] [ Lu ] 177 Lu]Method for stabilizing content of oxooctreotide injection - Google Patents
Determination of lutetium [ Lu ] [ Lu ] 177 Lu]Method for stabilizing content of oxooctreotide injection Download PDFInfo
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Abstract
The invention relates to the technical field of analysis and detection, in particular to a method for measuring lutetium by adopting a high performance liquid chromatography 177 Lu]Method for stabilizing content of oxooctreotide injection. The method provided by the invention comprises the following steps: the mobile phase A is sodium acetate solution, and the mobile phase B is methanol or acetonitrile; and a specific elution procedure. The detection method provided by the invention can simultaneously convert lutetium [ lutetium ], [ solution ] 177 Lu]The stabilizer vitamin C and gentisic acid in the oxooctreotide injection are separated, the analysis speed is high, and the separation degree is more than 1.5. The method has good specificity, accuracy, stability and reliability, and can be used for measuring and controlling the content of vitamin C and gentisic acid. Meanwhile, the establishment of the analysis method realizes the lutetium [ lutetium ], [ solution of lutetium ] and [ solution of lutetium ], [ solution of lutetium ] and [ solution of lutetium ] in the sample of the sample 177 Lu]Accurate detection of stabilizer content in oxooctreotide injection and accurate detection of stabilizer content in oxooctreotide injectionThe development and optimization of the process play an important guiding role.
Description
Technical Field
The invention relates to the technical field of analysis and detection, in particular to a method for measuring lutetium by adopting a high performance liquid chromatography 177 Lu]Method for stabilizing content of oxooctreotide injection.
Background
Lutetium [ lutetium ] 177 Lu]Oxooctreotide injection is a radiopharmaceutical used for treating somatostatin receptor positive gastrointestinal pancreatic neuroendocrine tumors. The radioactive drug has the characteristic of radiation self-decomposition, particles or rays emitted by radioactive isotopes can directly act on the radioactive drug, so that the structure of active molecules is changed, the biological activity of the active molecules is lost, the final treatment effect is influenced, 177 lu emits beta rays, and the radiolysis effect is more obvious.
To reduce radiolysis of the radiopharmaceutical product and increase the stability of the drug, lutetium [ lutetium ], [ solution ] 177 Lu]Vitamin C and gentisic acid are added into the oxooctreotide injection, and the content of the stabilizer has great influence on the quality, safety and effectiveness of the medicine, so that the content needs to be controlled.
The literature data temporarily does not contain lutetium 177 Lu]A method for measuring the content of gentisic acid and vitamin C in oxooctreotide injection. Referring to a determination method of vitamin C as an auxiliary material in the second department of China pharmacopoeia 2020 edition, the determination method is a titration method, and a measurement method of gentisic acid is not found temporarily.
However, the titration method is not applicable to lutetium [ 2 ] 177 Lu]Measurement of vitamin C content in Oxolotropin injection due to lutetium [ lutetium ], [ solution of lutetium ] of lutetium [ solution of lutetium ] of lutetium [ lutetium ] of luteo-of lutetium [ sic acid [ lutetium ] of an injection 177 Lu]The oxooctreotide injection has the characteristics of multiple components and radioactivity, and has the defects of multiple interference factors, large measurement error and radiation when the vitamin C is measured by a titration methodLarge injection dose and the like.
Disclosure of Invention
Aiming at the lack of lutetium in the prior art 177 Lu]The invention provides a method for effectively detecting the content of a stabilizing agent in an oxooctreotide injection, and provides a method for simultaneously detecting lutetium [ lutetium ], [ solution of lutetium ] and [ solution of lutetium ], [ solution of lutetium ] in an oxyoctreotide ] injection 177 Lu]High performance liquid chromatography method for stabilizing vitamin C and gentisic acid content in oxooctreotide injection. The method has better specificity, accuracy, stability and reliability, and can be used for lutetium [ lutetium ], [ lutetium ] 177 Lu]Measuring the content of the stabilizer in the oxooctreotide injection and controlling the quality.
The invention provides a method for measuring lutetium [ Lu ], [ solution ] by adopting high performance liquid chromatography 177 Lu]The method for stabilizing the content of the stabilizer in the oxooctreotide injection comprises the following steps: the mobile phase A is sodium acetate solution, and the mobile phase B is methanol or acetonitrile; the gradient elution procedure was as follows:
the high performance liquid chromatography is a common analysis and detection method in the field, has better accuracy and stability, and for this reason, the invention provides the method for detecting lutetium by using the high performance liquid chromatography 177 Lu]And detecting the contents of the stabilizing agents vitamin C and gentisic acid in the oxooctreotide injection.
When the high performance liquid chromatography is adopted for detection, a commonly used chromatographic column is a C18 reversed-phase chromatographic column, commonly used mobile phases are organic solvents such as methanol, acetonitrile, tetrahydrofuran, trifluoroacetic acid and the like, and a commonly used elution mode is isocratic elution. However, since lutetium [ 2 ] 177 Lu]The vitamin C serving as a stabilizer in the oxooctreotide injection is a strong polar substance, the gentisic acid serving as a weak polar substance has the characteristic of large polarity difference, and the vitamin C and the gentisic acid are difficult to separate under the conventional analysis conditions of the high performance liquid chromatography, or the vitamin C and the gentisic acid are difficult to separate, or the vitamin C and the gentisic acid are separated but have the problems of long analysis time or poor peak pattern, so that the detection result has large error and is unstable.
After a large number of experiments, the invention discovers that the retention time of the strong polar substance (vitamin C) on the C18 chromatographic column is short, but the retention time is weakThe retention time of the polar substance (gentisic acid) on the C18 chromatographic column is longer, and the retention time of vitamin C can be increased by selecting sodium acetate solution, methanol or acetonitrile as a mobile phase; meanwhile, the retention time of the gentisic acid on the chromatographic column can be obviously shortened by matching the gradient elution program, and lutetium [ lutetium ], [ solution of lutetium ] can be used as the main component 177 Lu]The radioactive main components in the oxooctreotide injection are washed out as soon as possible, so that the high-efficiency separation of the vitamin C and the gentisic acid is realized, the analysis speed is high, and the separation degree is more than 1.5.
Preferably, the concentration of the sodium acetate solution is 0.01-0.03 mol/L. Research shows that the concentration of the sodium acetate solution is reasonably controlled to ensure that the retention time of the vitamin C and the gentisic acid is in a proper range.
Further preferably, the pH of the mobile phase A is controlled to be between 3.3 and 3.7. Research shows that the pH value range of the mobile phase A is controlled, so that the mobile phase, gentisic acid and vitamin C are favorably prevented from being oxidized under an alkaline condition under an acidic condition.
In order to further improve the accuracy and stability of the detection result, other conditions of the high performance liquid chromatography are optimized, and the following optimization scheme is obtained:
octadecyl bonding organic hybrid silica gel is used as a filler for a chromatographic column; the size of the column was Shimadzu Shim-pack scanner C18-120, 4.6 mm. times.250 mm, 5 μm. Compared with other conventional fillers, the octadecyl bonding organic hybrid silica gel has the advantages of high column efficiency, good separation performance and good stability in a pH range of 2.0-9.0.
Flow rate: 0.8-1.2 mL/min; studies have shown that controlling the flow rate within this range facilitates the retention times of vitamin C and gentisic acid within the appropriate range.
Column temperature: 20-30 ℃.
Wavelength: 250-320 nm, preferably 295 nm.
Research shows that through the reasonable arrangement, lutetium [ lutetium ] can be simultaneously diluted without need 177 Lu]The oxooctreotide injection can accurately and quickly detect the contents of vitamin C and gentisic acid.
As the inventionIn a specific embodiment of the above, the assay is lutetium [ lutetium ], [ solution ] 177 Lu]The method for stabilizing the content of the stabilizer in the oxooctreotide injection comprises the following steps:
a) preparing a blank solution
Preparing a blank solution by taking a sodium acetate solution containing 0.01mol/L and methanol according to the volume ratio of 95: 5; or taking the water solution as a blank solution;
B) preparing vitamin C reference substance solution
Based on lutetium 2 177 Lu]Weighing 180mg of a vitamin C reference substance according to the theoretical content of the vitamin C in the oxooctreotide injection, dissolving the vitamin C reference substance in the blank solution, and fixing the volume to 10mL to prepare a reference substance solution of 18.0 mg/mL;
C) preparing gentisic acid reference substance solution
Based on lutetium 2 177 Lu]Weighing 15mg of gentisic acid reference substance according to the theoretical content of gentisic acid in the oxooctreotide injection, dissolving the gentisic acid reference substance in the blank solution, and fixing the volume to 25mL to prepare 0.6mg/mL reference substance solution;
D) preparing test solution
Taking appropriate amount of lutetium [ lutetium ], [ solution ] 177 Lu]The oxooctreotide injection is used as a test solution;
E) measurement method
Respectively injecting the blank solution, the vitamin C reference substance solution, the gentisic acid reference substance solution and the test sample solution into a chromatograph, and recording a chromatogram; and calculating the contents of vitamin C and gentisic acid in the test sample by an external standard method according to peak areas in chromatograms of the reference sample and the test sample.
The invention has the following beneficial effects:
the detection method provided by the invention can simultaneously convert lutetium [ lutetium ], [ solution of lutetium ] and [ solution of lutetium ], [ solution of lutetium ] and [ solution of lutetium ], [ solution of lutetium ] simultaneously 177 Lu]The stabilizer vitamin C and gentisic acid in the oxooctreotide injection are separated, the analysis speed is high, and the separation degree is more than 1.5. The methodological verification of system applicability, specificity, linearity and range, precision, accuracy and durability is carried out according to the verification guiding principle of the analysis method 9101 in the Chinese pharmacopoeia 2020 edition, and the method is proved to have better system applicability, specificity, accuracy, stability and reliability and can be used for the content of vitamin C and gentisic acidAnd (4) measurement and control. The establishment of the analysis method realizes the analysis of the lutetium [ lutetium ], ] 177 Lu]The content of the stabilizer in the oxooctreotide injection preparation is accurately detected, and an important guiding function is played for the development and optimization of a prescription process.
Drawings
FIG. 1 is a chromatogram of a blank solution of Experimental example 1 of the present invention.
FIG. 2 is a chromatogram of a vitamin C control solution in Experimental example 1 of the present invention.
FIG. 3 is a chromatogram of a control gentisic acid solution according to Experimental example 1 of the present invention.
FIG. 4 is a chromatogram of a solution suitable for use in the system of Experimental example 1 of the present invention.
FIG. 5 is a chromatogram of a sample solution in example 1 of the present invention.
FIG. 6 is a linear and range chromatogram of vitamin C according to example 1 of the present invention.
Fig. 7 is a linear and range chromatogram of gentisic acid in example 1 of the present invention.
FIG. 8 is a chromatogram of a control solution of vitamin C of comparative example 2 according to the present invention.
FIG. 9 is a chromatogram of a comparative example 3 vitamin C control solution of the present invention.
FIG. 10 is a chromatogram of a solution suitable for use in the comparative example 4 system of the present invention.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
Example 1
The embodiment provides a method for determining the content of a stabilizer in lutetium oxide octreotide injection by adopting a high performance liquid chromatography, which comprises the following steps of:
a) preparing a blank solution
Preparing a blank solution by taking a sodium acetate solution containing 0.01mol/L and methanol according to the volume ratio of 95: 5; or taking the water solution as a blank solution;
B) preparing vitamin C reference substance solution
Weighing 180mg of vitamin C reference substance, dissolving the vitamin C reference substance in the blank solution, and fixing the volume to 10mL to prepare 18.0mg/mL reference substance solution;
C) preparing gentisic acid reference substance solution
Weighing 15mg of gentisic acid reference substance, dissolving in the blank solution, and fixing the volume to 25mL to prepare a reference substance solution of 0.6 mg/mL;
D) preparing test solution
Taking appropriate amount of lutetium [ lutetium ], [ solution ] 177 Lu]The oxooctreotide injection is used as a test solution;
E) measurement method
Injecting the blank solution, the vitamin C reference substance solution, the gentisic acid reference substance solution and the test solution into a chromatograph respectively, and recording chromatograms; and calculating the contents of vitamin C and gentisic acid in the test sample by an external standard method according to peak areas in chromatograms of the reference sample and the test sample.
Wherein:
a chromatographic column: octadecyl bonding organic hybrid silica gel is used as a filling agent; the size of the column was Shimadzu Shim-pack scanner C18-120, 4.6 mm. times.250 mm, 5 μm.
A mobile phase A: 0.01mol/L sodium acetate solution (pH: 3.3-3.7);
mobile phase B: methanol;
column temperature: 20-30 ℃;
flow rate: 0.8-1.2 mL/min;
wavelength: 295 nm;
the gradient elution procedure was as follows:
instruments and reagents:
1260 II high performance liquid chromatograph, Agilent; XPR205/A electronic balance, Mettler corporation; HPLC column, Shimadzu Shim-pack scanner C18-120, 4.6mm X250 mm, 5 μm.
Vitamin C reference (SIGMA, batch: LRAC 2886); gentisic acid reference (Trc, batch number: 1-SWA-24-1); acetonitrile (chromatographically pure, national drug, batch number: 20201224); sodium acetate (analytically pure, national drug, lot number: 20210521); the ultrapure water is self-made by a laboratory ultrapure water machine.
Effect verification
The methodology of system applicability, specificity, linearity and range, precision, accuracy and durability of the method described in the examples is verified according to the Chinese pharmacopoeia 2020 edition 9101 analysis method verification guideline, which is as follows:
the specific preparation process of each solution in the example 1 and the test verification process and the result of the method of the invention are shown in the experimental examples 1-4.
Experimental example 1 System suitability test
Blank solution: preparing a blank solution by taking a sodium acetate solution containing 0.01mol/L and methanol according to the volume ratio of 95: 5; or taking the water solution as a blank solution;
vitamin C control solution: weighing 180mg of vitamin C reference substance, dissolving in the blank solution, and fixing the volume to 10mL to prepare 18.0mg/mL of vitamin C reference substance solution;
gentisic acid control solution: weighing 15mg of gentisic acid reference substance, dissolving in the blank solution, and fixing the volume to 25mL to prepare 0.6mg/mL gentisic acid reference substance solution;
system applicability solution: mixing a certain amount of vitamin C reference substance solution and gentisic acid reference substance solution.
And (3) determination: the column was eluted with a gradient of Shim-pack scanner C18-120(4.6 mm. times.250 mm, 5 μm), a detection wavelength of 295nm, a flow rate of 1.0mL/min, a column temperature of 25 ℃, a mobile phase A of 0.01mol/L sodium acetate solution (pH:3.5), and a mobile phase B of methanol.
Gradient elution is as follows:
injecting 5 μ l of each of the blank solution, vitamin C reference solution, gentisic acid reference solution and system applicability solution into a high performance liquid chromatograph, and recording chromatogram. The detection results of vitamin C and gentisic acid are shown in tables 1 and 2, the blank solution chromatogram is shown in figure 1, the vitamin C reference solution chromatogram is shown in figure 2, the gentisic acid reference solution chromatogram is shown in figure 3, and the system applicability solution chromatogram is shown in figure 4.
TABLE 1 systematic applicability-vitamin C assay results
TABLE 2 systematic applicability-gentisic acid assay results
And (4) conclusion: continuously feeding 6 needles of gentisic acid and vitamin C reference substance solution, wherein the theoretical plate number n of the main peak meets the requirement of being more than or equal to 3500; continuously injecting 6 needles of gentisic acid and vitamin C reference substance solution, wherein the retention time of a main peak and the relative standard deviation RSD (%) of the peak area both meet the requirement of being less than or equal to 2.0%; tailing factor T: continuously feeding 6-needle gentisic acid and vitamin C reference substance solutions, and taking peak areas as quantitative parameters, wherein the tailing factors T are less than or equal to 2; the separation degrees of gentisic acid and vitamin C in the systemic solution are both more than 1.5; shows that the high performance liquid chromatography provided by the invention is used for measuring lutetium [ 2 ] 177 Lu]The system applicability of the detection method for the content of vitamin C and gentisic acid in the oxooctreotide injection is good.
Experimental example 2 specificity
Test solution: taking appropriate amount of lutetium [ lutetium ], [ solution ] 177 Lu]Oxooctreotide injection is used as a test solution.
Injecting 5 mul of blank solution, vitamin C reference solution, gentisic acid reference solution, system applicability solution and sample solution into a high performance liquid chromatograph, and recording chromatogram. The results are shown in Table 3. The chromatogram of the blank solution is shown in FIG. 1, and the chromatogram of the test solution is shown in FIG. 5.
TABLE 3 specialization
And (4) conclusion: the blank solvent has no interference at the chromatographic peak positions of gentisic acid and vitamin C; the separation degree of gentisic acid and vitamin C in the systematic solution meets the requirement of being more than or equal to 1.5; the retention time of gentisic acid and vitamin C in the test solution is consistent with that of gentisic acid and vitamin C reference solution; shows that the high performance liquid chromatography provided by the invention is used for measuring lutetium [ lutetium ], [ solution of lutetium ] and [ solution of lutetium ] in the presence of a solvent of the high performance liquid chromatography 177 Lu]The method for detecting the content of vitamin C and gentisic acid in the oxooctreotide injection has good specificity.
Experimental example 3 Linear and Range testing
Vitamin C control solution: the vitamin C control product is diluted with ultrapure water to give concentrations of 30.0, 25.0, 20.0, 15.0, 10.0, 5.0, and 2.5 mg/ml.
Gentisic acid control solution: the gentisic acid control sample is diluted with ultrapure water to concentrations of 1.50, 1.20, 1.00, 0.80, 0.60, 0.30, and 0.15 mg/ml.
Injecting 5 mul of each of the vitamin C reference substance solutions with different concentrations into a high performance liquid chromatograph, recording a chromatogram, and taking the concentration of the vitamin C as a horizontal ordinate and the peak area of the vitamin C as a vertical coordinate to make a linear regression equation; and (3) injecting 5 mu l of each gentisic acid reference substance solution with different concentrations into a high performance liquid chromatograph, recording a chromatogram, and taking the concentration of gentisic acid as a horizontal coordinate and the peak area of gentisic acid as a vertical coordinate to make a linear regression equation. The results are shown in Table 4, and the linear and range chromatograms for vitamin C and gentisic acid are shown in FIGS. 6-7.
TABLE 4 Linearity and Range
| Composition (I) | Standard curve | Linearity and range | r |
| Vitamin C | y＝373.78x+563.28 | 2.5～30.0mg/mL | 0.995 |
| Gentisic acid | y＝2495.7x+7.8269 | 0.15～1.50mg/mL | 0.999 |
And (4) conclusion: the vitamin C is in the range of 2.5-30.0 mg/mL, the linear regression equation is that y is 373.78x +563.28, the correlation coefficient is 0.995, the requirement that r is more than or equal to 0.990 is met, and the linear relation between the peak area and the concentration is good. The gentisic acid is in the range of 0.15-1.50 mg/mL, the linear regression equation is that y is 2495.7x +7.8269, the correlation coefficient is 0.999, the requirement that r is more than or equal to 0.990 is met, and the linear relation between the peak area and the concentration is good.
EXAMPLE 4 precision
Repeatability: and taking 5 mu l of sample solution, continuously injecting 6 needles into the high performance liquid chromatograph, and recording the chromatogram. The results are shown in Table 5.
TABLE 5 repeatability results
Intermediate precision: another analyst takes 5 mul of the test solution, continuously samples 6 needles and injects into the high performance liquid chromatograph, and records the chromatogram. The results are shown in Table 6.
TABLE 6 intermediate precision results
And (4) conclusion: the peak retention time and the peak area RSD (%) of the vitamin C and the gentisic acid in the repeatability and intermediate precision tests are less than or equal to 2.0 percent, which shows that the repeatability and intermediate precision results are good.
Experimental example 5 accuracy
Simulation solution: a simulated solution containing vitamin C and gentisic acid was prepared.
And (5 mul of each simulation solution is taken, 6 needles of continuous sample introduction are injected into the high performance liquid chromatograph, and the chromatogram is recorded. The results are shown in tables 7 to 8.
TABLE 7 accuracy-vitamin C
TABLE 8 accuracy-gentisic acid
And (4) conclusion: the method is used for measuring 6 parts of simulated solution, wherein the recovery rates of the vitamin C and the gentisic acid are both between 90% and 108%, and the accuracy result is good.
Experimental example 6 durability
And (3) taking 5 mu l of the vitamin C reference substance solution, the gentisic acid reference substance solution and the test solution, injecting into a liquid chromatograph under various chromatographic conditions, and recording chromatograms, wherein the results are shown in tables 9-10.
TABLE 9 durability-vitamin C
TABLE 10 durability-gentisic acid
And (4) conclusion: changing the conditions of column temperature, flow rate and pH of the mobile phase A, wherein RSD of the ratio of the retention time and the peak area of the vitamin C in the test solution to the retention time and the peak area of the vitamin C reference solution is less than or equal to 2%, and RSD of the retention time and the peak area of the gentisic acid in the test solution to the retention time and the peak area of the gentisic acid reference solution is less than or equal to 2%, which indicates that the method has good durability.
Comparative example 1
When the content of vitamin C in a test solution in an embodiment is detected by adopting a titration method, the result shows that the measurement result is larger, the content measurement of the vitamin C is influenced because the titration liquid and gentisic acid also generate oxidation-reduction reaction during titration, and the required sample amount of the titration method is large, so that the radiation dose to personnel is large. Indicating that the titration method is not suitable for lutetium 177 Lu]And (3) measuring the content of vitamin C in the oxooctreotide injection.
Comparative example 2
This test provides a detection method which differs from the examples in that the chromatographic column is different, specifically Hypersil BDS C18(5 μm, 4.6X 250 mm). The results show that the retention time of vitamin C is too short, only 2.362 min. It is illustrated that when the chromatographic column is not properly selected, the detection error is large, and the result is shown in FIG. 8.
Comparative example 3
This test provides a detection method which differs from the examples in that the mobile phase A is different, specifically 0.01mol/L sodium dihydrogen phosphate solution. The results showed that the vitamin C had a poor peak pattern and the peaks were split. It is illustrated that when the mobile phase is not properly selected, the detection error is large, and the result is shown in fig. 9.
Comparative example 4
The test provides a detection method, which is different from the embodiment in that the elution mode is isocratic elution, specifically, 0.01mol/L sodium acetate solution and methanol with the volume ratio of 95: 5. The results showed that the retention time of gentisic acid was too long, 18.450min, and lutetium [ lutetium ], [ solution ] 177 Lu]The radioactive main component in the oxooctreotide injection cannot be washed out, and the analysis of vitamin C and gentisic acid is influenced during continuous sample injection, which indicates that the detection error is large during isocratic elution, and the result is shown in figure 10.
Although the invention has been described in detail hereinabove with respect to a general description and specific embodiments thereof, it will be apparent to those skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (8)
1. Determination of lutetium [ Lu ] [ Lu ] 177 Lu]The method for measuring the content of the stabilizer in the oxooctreotide injection is characterized by adopting a high performance liquid chromatography to measure;
wherein the mobile phase A is sodium acetate solution, and the mobile phase B is methanol or acetonitrile;
the gradient elution procedure was as follows:
2. the method according to claim 1, wherein the concentration of the sodium acetate solution is 0.01-0.03 mol/L.
3. The method according to claim 2, wherein the pH of the sodium acetate solution is controlled to be between 3.3 and 3.7.
4. The method as claimed in claim 3, wherein the chromatographic column uses octadecyl organic hybrid silica gel as filler.
5. The method of claim 4, wherein the size of the column is Shimadzu Shim-pack Shim C18-120, 4.6mm x 250mm, 5 μm.
6. The method according to claim 5, wherein the flow rate is 0.8-1.2 mL/min.
7. The method according to claim 6, wherein the column temperature is 20 ℃ to 30 ℃.
8. The method according to claim 7, wherein the wavelength is 250 to 320 nm.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5384113A (en) * | 1991-08-29 | 1995-01-24 | Mallinckrodt Medical, Inc. | Stabilizers to prevent autoradiolysis of radiolabeled peptides and proteins |
| US20070269375A1 (en) * | 2003-07-24 | 2007-11-22 | Bracco Imaging S.P.A. | Stable Radiopharmaceutical Compositions and Methods for Preparation |
| WO2008009444A1 (en) * | 2006-07-19 | 2008-01-24 | Van Dulmen, Adrianus, A. | Use of ethanol for stabilizing a single-vial liquid formulation of a radiolabeled peptide |
| WO2011147762A2 (en) * | 2010-05-25 | 2011-12-01 | Bayer Pharma Aktiengesellschaft | Stabilized radiopharmaceutical composition |
| US20200030465A1 (en) * | 2018-07-25 | 2020-01-30 | Advanced Accelerator Applications (Italy) Srl | Stable, concentrated radionuclide complex solutions |
| US20220008564A1 (en) * | 2020-07-13 | 2022-01-13 | Point Biopharma, Inc. | Radiopharmaceutical and methods |
| WO2022043754A2 (en) * | 2020-08-27 | 2022-03-03 | Centre For Probe Development Andcommercialization (Cpdc) | Radiopharmaceutical and methods |
-
2022
- 2022-07-14 CN CN202210834540.4A patent/CN115015441B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5384113A (en) * | 1991-08-29 | 1995-01-24 | Mallinckrodt Medical, Inc. | Stabilizers to prevent autoradiolysis of radiolabeled peptides and proteins |
| US20070269375A1 (en) * | 2003-07-24 | 2007-11-22 | Bracco Imaging S.P.A. | Stable Radiopharmaceutical Compositions and Methods for Preparation |
| WO2008009444A1 (en) * | 2006-07-19 | 2008-01-24 | Van Dulmen, Adrianus, A. | Use of ethanol for stabilizing a single-vial liquid formulation of a radiolabeled peptide |
| WO2011147762A2 (en) * | 2010-05-25 | 2011-12-01 | Bayer Pharma Aktiengesellschaft | Stabilized radiopharmaceutical composition |
| US20200030465A1 (en) * | 2018-07-25 | 2020-01-30 | Advanced Accelerator Applications (Italy) Srl | Stable, concentrated radionuclide complex solutions |
| US20220008564A1 (en) * | 2020-07-13 | 2022-01-13 | Point Biopharma, Inc. | Radiopharmaceutical and methods |
| WO2022043754A2 (en) * | 2020-08-27 | 2022-03-03 | Centre For Probe Development Andcommercialization (Cpdc) | Radiopharmaceutical and methods |
Non-Patent Citations (2)
| Title |
|---|
| 吴琼珠 等: "高效液相色谱法测定奥曲肽注射液的含量", 中国生化药物杂志, vol. 23, no. 3, pages 144 - 145 * |
| 韩振义 等: "64Cu标记两种奥曲肽类似物的比较", 同位素, vol. 29, no. 2, pages 82 - 88 * |
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