CN108107120B - Method for measuring intermediate product 6, 6-dibromo penicillanic acid by adopting high performance liquid chromatography - Google Patents
Method for measuring intermediate product 6, 6-dibromo penicillanic acid by adopting high performance liquid chromatography Download PDFInfo
- Publication number
- CN108107120B CN108107120B CN201711314978.5A CN201711314978A CN108107120B CN 108107120 B CN108107120 B CN 108107120B CN 201711314978 A CN201711314978 A CN 201711314978A CN 108107120 B CN108107120 B CN 108107120B
- Authority
- CN
- China
- Prior art keywords
- buffer solution
- ammonium acetate
- acetate buffer
- intermediate product
- high performance
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- OSORMYZMWHVFOZ-UHFFFAOYSA-N phenethyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCCC1=CC=CC=C1 OSORMYZMWHVFOZ-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims abstract description 35
- 239000013067 intermediate product Substances 0.000 title claims abstract description 20
- 238000004128 high performance liquid chromatography Methods 0.000 title claims abstract description 14
- 239000007853 buffer solution Substances 0.000 claims abstract description 25
- 238000001514 detection method Methods 0.000 claims abstract description 25
- 239000012071 phase Substances 0.000 claims abstract description 19
- XORXDJBDZJBCOC-UHFFFAOYSA-N azanium;acetonitrile;acetate Chemical compound [NH4+].CC#N.CC([O-])=O XORXDJBDZJBCOC-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000012086 standard solution Substances 0.000 claims abstract description 10
- 238000012360 testing method Methods 0.000 claims abstract description 10
- 239000007791 liquid phase Substances 0.000 claims abstract description 5
- 239000012085 test solution Substances 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 15
- 239000005695 Ammonium acetate Substances 0.000 claims description 15
- 229940043376 ammonium acetate Drugs 0.000 claims description 15
- 235000019257 ammonium acetate Nutrition 0.000 claims description 15
- 238000010828 elution Methods 0.000 claims description 7
- 238000010829 isocratic elution Methods 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000011084 recovery Methods 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 6
- 239000008055 phosphate buffer solution Substances 0.000 abstract description 4
- FOHSWKNHIIJOPU-UHFFFAOYSA-L [Na+].[Na+].CC#N.OP([O-])([O-])=O Chemical compound [Na+].[Na+].CC#N.OP([O-])([O-])=O FOHSWKNHIIJOPU-UHFFFAOYSA-L 0.000 abstract description 2
- OQKFGIANPCRSSK-UHFFFAOYSA-N azanium;methanol;acetate Chemical compound [NH4+].OC.CC([O-])=O OQKFGIANPCRSSK-UHFFFAOYSA-N 0.000 abstract description 2
- 238000012937 correction Methods 0.000 abstract description 2
- HQNFNXUJTAXVER-UHFFFAOYSA-L disodium hydrogen phosphate methanol Chemical compound [Na+].[Na+].OC.OP([O-])([O-])=O HQNFNXUJTAXVER-UHFFFAOYSA-L 0.000 abstract description 2
- 239000011159 matrix material Substances 0.000 abstract description 2
- 230000014759 maintenance of location Effects 0.000 description 15
- NKZMPZCWBSWAOX-IBTYICNHSA-M Sulbactam sodium Chemical compound [Na+].O=S1(=O)C(C)(C)[C@H](C([O-])=O)N2C(=O)C[C@H]21 NKZMPZCWBSWAOX-IBTYICNHSA-M 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 229960000614 sulbactam sodium Drugs 0.000 description 9
- 239000012535 impurity Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 2
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000003781 beta lactamase inhibitor Substances 0.000 description 2
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Sampling And Sample Adjustment (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention belongs to the field of chemical detection, and particularly relates to a method for determining an intermediate product 6, 6-dibromo penicillanic acid by adopting a high-efficiency liquid phase method. Determining high performance liquid chromatography detection conditions, wherein a mobile phase is one of methanol-disodium hydrogen phosphate buffer solution, acetonitrile-disodium hydrogen phosphate buffer solution, methanol-ammonium acetate buffer solution or acetonitrile-ammonium acetate buffer solution; the chromatographic column is a C18 chromatographic column; respectively preparing a standard solution and a test solution of 6, 6-dibromopenicillanic acid; making a standard curve; and calculating the content of the test sample. The result shows that the content of the 6, 6-dibromopenicillanic acid has a good linear relation in the concentration range of 0.1-1.2 mg/ml, the correlation coefficient is 0.9997, and the average recovery rate of the 6, 6-dibromopenicillanic acid is more than 90 percent and the relative standard deviation is less than 2.0 percent by adopting a method of blank matrix matching with a standard solution to carry out standard correction. The detection method is simple and convenient to operate, and has good chromatographic peak shape, accurate and reliable data and good reproducibility.
Description
Technical Field
The invention belongs to the field of chemical detection, and particularly relates to a method for determining an intermediate product 6, 6-dibromo penicillanic acid by adopting a high-efficiency liquid phase method.
Background
Sulbactam sodium is an irreversible competitive beta-lactamase inhibitor which is artificially synthesized, is firstly developed by the American Pfizer research room, is usually combined with penicillin or cephalosporin medicaments to prevent the penicillin or cephalosporin medicaments from being damaged by beta-lactamase, enhances the antibacterial activity, and is suitable for infection of respiratory systems, urinary systems, skin soft tissues and the like. Beta-lactamase inhibitors have brought the entire range of beta-lactam antibiotics into a new era in overcoming serious drug-resistant bacterial infections.
According to the report of literature data, the sulbactam sodium is synthesized by adopting 6-aminopenicillanic acid as a raw material and carrying out diazotization, bromination, oxidation, reduction and salification. The method has already realized the industrialized mass production, but the detection method about the intermediate product generated in the sulbactam sodium synthesis process has not been published with the current detection standard at home and abroad, the foreign target is mainly put into the use condition of the finished product in clinical medical treatment due to the difference of the cultural development degree, and the reports of the related detection method of the intermediate product are few.
Because no good and effective detection means exist at present, establishing a method for detecting the content of the intermediate product 6, 6-dibromo penicillanic acid generated when 6-APA is used as a starting material to synthesize sulbactam sodium is very important.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a method for measuring an intermediate product 6, 6-dibromo penicillanic acid by adopting a high-efficiency liquid phase method. The method has the advantages of simple and convenient operation, good chromatographic peak shape, accurate and reliable data and good reproducibility, not only can accurately measure the content of the 6, 6-dibromopenicillanic acid, but also can control the content of other impurities in the product, and plays a guiding role in the production of subsequent intermediate products and sulbactam sodium.
The method for measuring the intermediate product 6, 6-dibromo penicillanic acid by adopting the high-efficiency liquid phase method specifically comprises the following steps:
(1) determining high performance liquid chromatography detection conditions, wherein the mobile phase is one of methanol-disodium hydrogen phosphate buffer solution, acetonitrile-disodium hydrogen phosphate buffer solution, methanol-ammonium acetate buffer solution or acetonitrile-ammonium acetate buffer solution; the chromatographic column is a C18 chromatographic column;
(2) respectively preparing a standard solution and a test solution of 6, 6-dibromopenicillanic acid;
(3) making a standard curve;
(4) and calculating the content of the test sample.
Wherein:
the detection conditions of the high performance liquid chromatography are as follows: the column was a 250 x 4.6mm, 5 μm C18 column; the mobile phase is acetonitrile-ammonium acetate buffer solution; the flow rate is 0.8-1.3 ml/min; the detector wavelength is 225-235 nm; the column temperature is 25-35 ℃ and the sample injection volume is 20 mu L.
The volume ratio of acetonitrile to ammonium acetate in the mobile phase acetonitrile-ammonium acetate buffer solution is 25-35: 65-75.
The volume ratio of acetonitrile to ammonium acetate in the mobile phase acetonitrile-ammonium acetate buffer solution is 30: 70.
The elution mode in the detection condition of the high performance liquid chromatography is isocratic elution, and the elution time is 15 min.
The mass fraction of the ammonium acetate buffer solution in the mobile phase is 0.07-0.09%.
The mass fraction of the ammonium acetate buffer solution in the mobile phase was 0.08%.
The temperature of the chromatographic column is 30 ℃; the detector wavelength is 230 nm; the flow rate was 1.0 ml/min.
As a preferable technical scheme, the method for determining the intermediate product 6, 6-dibromopenicillanic acid by using the high performance liquid chromatography method specifically comprises the following steps:
(1) the determination was carried out by high performance liquid chromatography according to the following chromatographic conditions: the chromatographic column is a 250 x 4.6mm, 5 μm C18 chromatographic column; the detection wavelength is 225-235 nm; the mobile phase is acetonitrile-ammonium acetate buffer solution; the flow rate is 0.8-1.3 ml/min; the sample amount is 20 mul; the elution time was 20 min.
(2) The volume ratio of the mobile phase acetonitrile to the ammonium acetate buffer solution is 30: 70.
(3) Buffer solution: ammonium acetate solution with the mass fraction of 0.08 percent.
(4) And (3) an elution mode: isocratic elution.
Through tests, under the optimal liquid chromatography condition, the content of 6, 6-dibromopenicillanic acid has a good linear relation in a concentration range of 0.1-1.2 mg/ml, the correlation coefficient is above 0.999, standard correction is performed by adopting a method of blank matrix matching with a standard solution, the average recovery rate of 6, 6-dibromopenicillanic acid is above 90%, and the relative standard deviation is less than 2.0%. The method is suitable for measuring the content of 6, 6-dibromo penicillanic acid which is an intermediate product in the synthesis of sulbactam sodium.
The invention has the following beneficial effects:
(1) the detection method is simple and convenient to operate, and has good chromatographic peak shape, accurate and reliable data and good reproducibility;
(2) the method not only can accurately measure the content of the 6, 6-dibromo penicillanic acid, but also can control the content of other impurities in the product, and plays a guiding role in the production of subsequent intermediate products and sulbactam sodium.
Drawings
FIG. 1 is a high performance liquid chromatogram of example 1 of the present invention;
FIG. 2 is a graph showing the concentration-peak area standard of 6, 6-dibromopenicillanic acid of the present invention.
Detailed Description
The present invention is further described below with reference to examples.
Example 1
1. The chromatographic detection conditions are as follows:
the column was a C18(250 × 4.6mm, 5 μm) column; the detection wavelength is 230nm, and the mobile phase is acetonitrile-ammonium acetate buffer solution (the volume ratio of acetonitrile to ammonium acetate is 30: 70); the mass fraction of the ammonium acetate buffer solution is 0.08%; the flow rate is 1.0 ml/min; the sample amount is 20 mul; the elution time was 15 min.
2. The testing steps are as follows:
(1) preparation of standard solution and drawing of standard curve
Accurately weighing 50.0mg of a 6, 6-dibromopenicillanic acid standard substance, placing the 6, 6-dibromopenicillanic acid standard substance into a 50ml volumetric flask, adding a mobile phase for dilution, fixing the volume to a scale, shaking up, and preparing into a standard solution with the concentration of 1 mg/ml; respectively and precisely weighing 2ml, 4ml, 6ml, 8ml and 10ml of the standard solution, placing the standard solution into a 10ml volumetric flask, metering the volume to 10ml by using a mobile phase, and preparing a 6, 6-dibromopenicillanic acid standard solution with the concentration of 0.2mg/ml, 0.4mg/ml, 0.6mg/ml, 0.8mg/ml and 1.0 mg/ml; and (4) injecting and measuring under the optimal chromatographic conditions. And (4) carrying out parallel determination on each concentration for 5 times, and making a standard curve according to the obtained peak area average value to the concentration of the 6, 6-dibromopenicillanic acid to obtain a regression equation and a correlation coefficient diagram.
Y＝750968X+5023；
R2＝0.9997。
(2) Preparation of test solution
Precisely weighing 50.0mg of the sample, placing the sample in a 50ml volumetric flask, adding the mobile phase for dissolving to a constant volume, standing and testing.
(3) Determination of 6, 6-dibromopenicillanic acid
The content of the 6, 6-dibromo penicillanic acid is 80.743% by measuring according to the high performance liquid chromatography conditions.
And (4) conclusion: as can be seen from the attached figure 1, the peak pattern is good, the solvent has no influence on the main peak and other impurity peaks, and the retention time of the 6, 6-dibromopenicillanic acid standard substance under the optimal chromatographic condition is basically consistent with that of the sulbactam sodium intermediate product, so that the optimal chromatographic condition is suitable for the detection of the sulbactam sodium intermediate product; as can be seen from FIG. 2, the standard curve of 6, 6-dibromopenicillanic acid is good in linearity, R2＝0.9997。
Examples 2 to 6
The detection methods of examples 2-6 are the same as in example 1, except that the buffer solution is ammonium acetate, the concentration of the ammonium acetate solution is different, resulting in different retention times, and the retention time data of 6, 6-dibromopenicillanic acid is shown in the following table 1:
TABLE 1 data table of 6, 6-dibromopenicillanic acid retention times for examples 2-6
The results show that in a certain concentration range, the retention time is prolonged along with the increase of the concentration of the buffer solution, the retention time is not suitable to be too long or too short, and the mobile phase with relatively low concentration of the buffer solution is selected on the premise of ensuring the separation effect, and the test determines that the optimal concentration of the ammonium acetate buffer solution is 0.08 percent by mass.
Examples 7 to 9
The detection method of examples 7-9 is the same as in example 1, except that the detector wavelength used is different, resulting in different retention times, and the retention time data for 6, 6-dibromopenicillanic acid is given in table 2 below:
TABLE 2 data table of 6, 6-dibromopenicillanic acid retention times for examples 7-9
| Wavelength/nm | 6, 6-dibromo-penicillanic acid retention time/min |
| 225 | 5.426 |
| 230 | 3.348 |
| 235 | 2.054 |
The results show that the ultraviolet absorption intensity of 6, 6-dibromo penicillanic acid is stronger when the ultraviolet absorption wavelength is 225-235nm, and therefore, 230nm is preferably used as the detection wavelength of the 6, 6-dibromo penicillanic acid in the test.
Examples 10 to 15
The detection methods of examples 10-15 are the same as in example 1, except that the flow rates used for detection by HPLC were different, resulting in different retention times, and the retention time data for 6, 6-dibromopenicillanic acid are shown in Table 3 below:
TABLE 3 data table of 6, 6-dibromopenicillanic acid retention times for examples 10-15
| Flow rate/(ml/min) | 6, 6-dibromo-penicillanic acid retention time/min |
| 0.2 | 8.738 |
| 0.3 | 6.937 |
| 0.7 | 4.429 |
| 1.0 | 3.348 |
| 1.3 | 2.264 |
| 2.0 | 1.108 |
The result shows that in the process of changing the flow rate from 0.2 to 2.0ml/min, the retention time is very long when the flow rate is lower than 0.7ml/min, the separation effect of the substance to be detected is influenced when the flow rate is higher than 1.3ml/min, and impurities and 6, 6-dibromo penicillanic acid are not completely separated. Therefore, the preferred flow rate for this test is 1.0 ml/min.
The test adopts a blank standard adding method to measure the recovery rate and the precision. Standards of 3 concentrations of 0.2mg/ml, 0.4mg/ml and 0.6mg/ml were added to the blank samples, each concentration sample was measured 5 times, the peak areas were recorded, and the results were entered into the regression equation, and the recovery and RSD were calculated according to the formula, respectively, and the results are shown in table 4.
TABLE 4 Standard sample recovery and RSD statistics
| Standard addition amount (mg/ml) | Sample measurement value (mg/ml) | Recovery (%) | RSD(％) |
| 0.2 | 0.1906 | 95.30 | 1.101 |
| 0.4 | 0.3712 | 92.80 | 0.987 |
| 0.6 | 0.5681 | 94.68 | 1.058 |
As can be seen from Table 4, the recovery rate of the method is more than 90%, and the RSD of the 6, 6-dibromopenicillanic acid peak area is less than 2.0%, so that the recovery rate and the system precision of the method are good.
Claims (5)
1. A method for measuring an intermediate product 6, 6-dibromo penicillanic acid by adopting a high performance liquid phase method is characterized by comprising the following steps: the method specifically comprises the following steps:
1) determining high performance liquid chromatography detection conditions, wherein a chromatographic column is a C18 chromatographic column;
2) respectively preparing a standard solution and a test solution of 6, 6-dibromopenicillanic acid;
3) making a standard curve;
4) calculating the content of the test sample;
wherein:
the mobile phase in the detection condition of the high performance liquid chromatography is acetonitrile-ammonium acetate buffer solution;
the elution mode in the detection condition of the high performance liquid chromatography is isocratic elution, and the elution time is 15 min;
the volume ratio of acetonitrile to ammonium acetate buffer solution in the mobile phase acetonitrile-ammonium acetate buffer solution is 25-35: 65-75;
the mass fraction of the ammonium acetate buffer solution in the mobile phase is 0.07-0.09%.
2. The method for determining 6, 6-dibromopenicillanic acid as an intermediate product according to claim 1, wherein the method comprises the following steps: the detection conditions of the high performance liquid chromatography are as follows: the column was a 250 x 4.6mm, 5 μm C18 column; the flow rate is 0.8-1.3 ml/min; the detector wavelength is 225-235 nm; the column temperature is 25-35 ℃ and the sample injection volume is 20 mu L.
3. The method for determining 6, 6-dibromopenicillanic acid as an intermediate product according to claim 1, wherein the method comprises the following steps: the volume ratio of acetonitrile to ammonium acetate buffer solution in the mobile phase acetonitrile-ammonium acetate buffer solution is 30: 70.
4. The method for determining 6, 6-dibromopenicillanic acid as an intermediate product according to claim 1, wherein the method comprises the following steps: the mass fraction of the ammonium acetate buffer solution in the mobile phase was 0.08%.
5. The method for determining 6, 6-dibromopenicillanic acid as an intermediate product according to claim 2, wherein the method comprises the following steps: the temperature of the chromatographic column is 30 ℃; the detector wavelength is 230 nm; the flow rate was 1.0 ml/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711314978.5A CN108107120B (en) | 2017-12-12 | 2017-12-12 | Method for measuring intermediate product 6, 6-dibromo penicillanic acid by adopting high performance liquid chromatography |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711314978.5A CN108107120B (en) | 2017-12-12 | 2017-12-12 | Method for measuring intermediate product 6, 6-dibromo penicillanic acid by adopting high performance liquid chromatography |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108107120A CN108107120A (en) | 2018-06-01 |
| CN108107120B true CN108107120B (en) | 2020-12-01 |
Family
ID=62209606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711314978.5A Active CN108107120B (en) | 2017-12-12 | 2017-12-12 | Method for measuring intermediate product 6, 6-dibromo penicillanic acid by adopting high performance liquid chromatography |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108107120B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0061313A2 (en) * | 1981-03-23 | 1982-09-29 | Pfizer Inc. | Bis-esters of 1,1-alkanediols with 6-beta-hydroxymethylpenicillanic acid 1,1-dioxide and beta-lactam antibiotics |
| WO2003087105A1 (en) * | 2002-04-04 | 2003-10-23 | Alamx, L.L.C. | INHIBITORS OF SERINE AND METALLO-ß-LACTAMASES |
| CN104215697A (en) * | 2013-05-29 | 2014-12-17 | 湘北威尔曼制药股份有限公司 | Method for detecting related substances in piperacillin sodium and sulbactum sodium for injection |
-
2017
- 2017-12-12 CN CN201711314978.5A patent/CN108107120B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0061313A2 (en) * | 1981-03-23 | 1982-09-29 | Pfizer Inc. | Bis-esters of 1,1-alkanediols with 6-beta-hydroxymethylpenicillanic acid 1,1-dioxide and beta-lactam antibiotics |
| WO2003087105A1 (en) * | 2002-04-04 | 2003-10-23 | Alamx, L.L.C. | INHIBITORS OF SERINE AND METALLO-ß-LACTAMASES |
| CN104215697A (en) * | 2013-05-29 | 2014-12-17 | 湘北威尔曼制药股份有限公司 | Method for detecting related substances in piperacillin sodium and sulbactum sodium for injection |
Non-Patent Citations (3)
| Title |
|---|
| TLC、GC、HPLC3种方法检测二溴青霉烷酸、二溴青霉烷砜酸和青霉烷砜酸;陈志华;《药物分析杂志》;19981230(第S1期);第312-314页 * |
| 聚乙二醇催化合成6,6-二溴青霉烷酸;李士杰;《精细石油化工》;20040229(第1期);第34-36页 * |
| 青霉烯关键医药中间体——氮杂环丁酮的合成;李士杰;《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》;20040915(第3期);第B016-35页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108107120A (en) | 2018-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109374781B (en) | Method for detecting related substances in mezlocillin sodium and sulbactam sodium for injection | |
| CN113740446B (en) | Cefaclor oxime and related substance analysis method for maintaining degradation quality of preparation content | |
| CN113588837B (en) | Detection method of moxifloxacin hydrochloride related substance | |
| CN108107120B (en) | Method for measuring intermediate product 6, 6-dibromo penicillanic acid by adopting high performance liquid chromatography | |
| CN103645151B (en) | A kind of method of spectinomycin content in quick mensuration spectinomycin fermented liquid or finished product | |
| CN107941977B (en) | High performance liquid phase analysis method of tazobactam diphenylmethyl ester serving as tazobactam intermediate product | |
| CN113030285B (en) | Method for detecting residual 2-bromomethyl-1, 3-dioxolane in doxofylline | |
| CN111650322A (en) | Method for detecting methyl acetoacetate in cefradine | |
| CN108072717B (en) | Method for detecting arginine solution | |
| CN109030653B (en) | Detection method of related substances in levofolinic acid | |
| CN114324642B (en) | Method for determining dextromethorphan hydrobromide related substances | |
| CN112034066B (en) | Method for separating and measuring Ribociclib and impurities | |
| CN107621512B (en) | Method for determining purity of cefaclor side chain acyl chloride by pre-column derivatization method | |
| CN110208397B (en) | High performance liquid chromatography for simultaneously determining contents of two main drugs in oxytetracycline and flunixin injection | |
| CN116265937A (en) | Detection method and application of oseltamivir phosphate related impurities | |
| CN109001342B (en) | High performance liquid chromatography method for detecting N-2, 3-dimethoxybenzyl piperonylethylamine and salt content thereof | |
| CN113504317A (en) | Detection method and application of genotoxic impurities in apixaban | |
| CN110824062A (en) | Detection method of related substances of tildipirosin intermediate | |
| CN111679004A (en) | Quality control method of probucol | |
| CN111521693B (en) | Method for detecting isosorbide mononitrate | |
| CN107894468B (en) | High performance liquid chromatography determination method of penicillanic sulfoxide acid diphenylmethyl ester | |
| CN113933409B (en) | Method for detecting terlipressin Li Shan antibody in serum based on liquid chromatography-mass spectrometry | |
| CN112611819B (en) | Method for measuring related substances in benfotiamine raw material and preparation thereof | |
| CN114200050B (en) | HPLC detection method for content of related substances in p-bromoanisole | |
| CN117269357B (en) | Detection method for determining impurity C in Argatroban |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20201113 Address after: 256100 Yiyuan Economic Development Zone, Shandong, Zibo Applicant after: SHANDONG XINQUAN PHARMACEUTICAL Co.,Ltd. Address before: 256100 Yiyuan Economic Development Zone, Shandong, Zibo Applicant before: ZIBO XINQUAN PHARMACEUTICAL TECHNOLOGY SERVICE Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A method for the determination of 6,6-dibromo penicillanic acid by HPLC was developed Effective date of registration: 20211216 Granted publication date: 20201201 Pledgee: Commercial Bank of China Yiyuan branch of Limited by Share Ltd. Pledgor: SHANDONG XINQUAN PHARMACEUTICAL Co.,Ltd. Registration number: Y2021980015204 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20220721 Granted publication date: 20201201 Pledgee: Commercial Bank of China Yiyuan branch of Limited by Share Ltd. Pledgor: SHANDONG XINQUAN PHARMACEUTICAL Co.,Ltd. Registration number: Y2021980015204 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Method for determination of intermediate product 6,6-dibromopencillanic acid by HPLC Effective date of registration: 20221231 Granted publication date: 20201201 Pledgee: Agricultural Bank of China Limited by Share Ltd. Yiyuan county subbranch Pledgor: SHANDONG XINQUAN PHARMACEUTICAL Co.,Ltd. Registration number: Y2022980029922 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |