CN110361475A - The detection method of polymer in a kind of measurement cephalosporin analog antibiotic - Google Patents
The detection method of polymer in a kind of measurement cephalosporin analog antibiotic Download PDFInfo
- Publication number
- CN110361475A CN110361475A CN201910718620.1A CN201910718620A CN110361475A CN 110361475 A CN110361475 A CN 110361475A CN 201910718620 A CN201910718620 A CN 201910718620A CN 110361475 A CN110361475 A CN 110361475A
- Authority
- CN
- China
- Prior art keywords
- antibiotic
- solution
- diluent
- reference substance
- polymer
- 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.)
- Pending
Links
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
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N2030/062—Preparation extracting sample from raw material
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)
- Cephalosporin Compounds (AREA)
Abstract
The present invention provides a kind of detection method for measuring polymer in cephalosporin analog antibiotic, belongs to detection technique field, steps are as follows: purified water S1, being placed 2-8 DEG C of refrigerator, takes out diluent, that is, blank solution is made before use；S2, take antibiotic A reference substance appropriate, dissolved with diluent and quantify dilution be made in every 1ml containing about the solution of 1mg antibiotic A；Take antibiotic B reference substance appropriate, dissolved with diluent and quantify dilution be made in every 1ml containing about the solution of 0.2mg antibiotic B；Antibiotic A:B (5:1) appropriate test sample is taken, is dissolved with diluent and quantifies dilution and be made in every 1ml containing about the solution of 1mg antibiotic A (containing about 0.2mg antibiotic B)；Precision measures test solution 1ml, sets in 100ml measuring bottle, adds diluent to be diluted to scale and shake up；S3, solution sample introduction, record chromatogram, and reading numerical values complete detection.The present invention has the advantages that easy to operate, specificity is strong, high sensitivity.
Description
Technical field
The invention belongs to detection technique fields, and in particular to a kind of detection side for measuring polymer in cephalosporin analog antibiotic
Method.
Background technique
High molecular polymer in cephalosporin analog antibiotic means that its middle-molecular-weihydroxyethyl is greater than the general name of the impurity of drug itself,
Molecular weight is individual up to 10000Da or so generally in 1000~5000Da.Since high molecular polymer has height inhomogeneity
And uncertainty, the reference substance with constant concentration, the uncharged related assays method of current edition " United States Pharmacopeia " can not be prepared.
2015 version " Chinese Pharmacopoeia " record with External standard method quantitative determination beta-lactam antibacterials in polyphosphazene polymer
The method for closing object replaces high molecular polymer reference substance to wherein by the conversion of two kinds of mobile phases with drug own control product
High molecular polymer detected, be currently used technology, for detecting polymer in cephalosporin analog antibiotic；
But the above method provided under version " Chinese Pharmacopoeia " Cefotaxime Sodium item according to 2015, used with sephadex G-
10 are measured the content of the high molecular polymer in cephalosporin analog antibiotic for the gel chromatographic columns of filler.The result shows that
The column effect of the chromatographic column is low (column effect only 1000 or so), and sample introduction concentration is high (20mg/ml), peak shape hangover, and analysis time is (one long
Sample needs 2h or so), (all high molecular polymers are a peak to inferior separating effect, and the peak and main peak fail to reach baseline
Separation), cause the detected level of high molecular polymer very low；
Summary of the invention
In view of the above deficiencies, the object of the present invention is to provide a kind of detection sides of polymer in measurement cephalosporin analog antibiotic
Method has the advantages that easy to operate, specificity is strong, high sensitivity.
The present invention provides the following technical solutions:
The detection method of polymer, includes the following steps: in a kind of measurement cephalosporin analog antibiotic
S1, purified water is placed 8 DEG C of refrigerator, takes out diluent, that is, blank solution is made before use；
S2, it prepares antibiotic A reference substance solution: taking antibiotic A reference substance appropriate, dissolved with diluent and quantify dilution system
At the solution in every 1ml containing about 1mg antibiotic A；It prepares antibiotic B reference substance solution: taking antibiotic B reference substance appropriate, use is dilute
Release agent dissolve and quantify dilution be made in every 1ml containing about the solution of 0.2mg antibiotic B；It prepares test solution: taking antibiotic A:
B (5:1) appropriate test sample, dissolved with diluent and quantify dilution be made in every 1ml it is (anti-containing about 0.2mg containing about 1mg antibiotic A
Raw element B) solution；Prepare contrast solution: precision measures test solution 1ml, sets in 100ml measuring bottle, diluent is added to be diluted to
Scale simultaneously shakes up；
S3, blank solution, antibiotic A reference substance solution, antibiotic B reference substance solution, appropriate test solution are taken respectively
Sample introduction, records chromatogram, and reading numerical values complete detection.
Preferably, chromatographic condition is as follows, chromatographic column: TSK-GEL G2000SWXL gel chromatographic columns (30cm × 7.8mm, 5 μ
m)；Mobile phase: 0.01mol/L phosphate buffer；Flow velocity: 1.0ml/min；Detection wavelength: 254nm；Sample volume: 10 μ l；Column
Temperature: 25 DEG C；Sample injection disc temperature: 4 DEG C.
Preferably, mobile phase is made by following methods: 0.01mol/L sodium dihydrogen phosphate；0.01mol/L disodium hydrogen phosphate
(61: 39, V/V) adjusts pH to 7.0 with 5mol/L sodium hydroxide solution.
The beneficial effects of the present invention are:
Since the high molecular polymer in antibiotic is the main reason for generating allergic reaction, control beta-lactam is anti-
High molecular polymer content in raw element, it is ensured that clinical application it is safe and effective.Foreign pharmacopeia there is no effective control at present
The detection means of macromolecule impurity.It is high in the External standard method quantitative determination beta-lactam antibiotic that Chinese Pharmacopoeia records
The detection method of polymers replaces the confrontation of macromolecule impurity reference substance by the conversion of two kinds of mobile phases with drug own control product
High polymer in raw element is detected, solve the problems, such as to a certain extent it is external insurmountable, but aforesaid way disadvantage compared with
It is more, and the present invention compensates for above-mentioned deficiency, overcomes above-mentioned many difficult points, the high polymer measurement being more suitable in antibiotic,
Have the advantages that easy to operate, specificity is strong, high sensitivity.
Detailed description of the invention
Attached drawing is used to provide further understanding of the present invention, and constitutes part of specification, with reality of the invention
It applies example to be used to explain the present invention together, not be construed as limiting the invention.In the accompanying drawings:
Fig. 1 is blank solution chromatogram；
Fig. 2 is antibiotic A reference substance solution chromatogram；
Fig. 3 is antibiotic B reference substance solution chromatogram；
Fig. 4 is test solution chromatogram；
Fig. 5 is the linear linear graph for investigating experiment；
Specific embodiment
Exclusion chromatography is also referred to as steric exclusion chromatography or gel permeation chromatography, be a kind of size according to sample molecule into
The isolated chromatographic technique of row.The filler of the chromatographic column of exclusion chromatography is gel, it is a kind of surface inertness, containing there are many different rulers
Very little hole or solid netted substance.The component molecular that the hole of gel only allows diameter to be less than hole aperture enters, this some holes pair
It is sizable for mobile phase molecule, so that mobile phase molecule can freely spread discrepancy.To different size of component
Molecule can penetrate into the different depth in gel pore respectively, and big component molecular can penetrate into the macropore of gel, but into
Aperture is not even ostracised completely.Small component molecular, macropore aperture can penetrate into, even into very deep, a period of time
It is not easy to be eluted out.Therefore, the residence time is shorter in the chromatography column for big component molecular, is eluted out quickly, its elution
Volume very little, the residence time is longer in the chromatography column for small component molecular, and elution volume is larger, until the minimum in all holes point
Son reaches column outlet, completes the elution process isolated by molecular size
The detection method of polymer in a kind of measurement cephalosporin analog antibiotic, steps are as follows:
S1, purified water is placed 2-8 DEG C of refrigerator, takes out diluent, that is, blank solution is made before use
S2, it prepares antibiotic A reference substance solution: taking antibiotic A reference substance appropriate, dissolved with diluent and quantify dilution system
At the solution in every 1ml containing about 1mg antibiotic A；It prepares antibiotic B reference substance solution: taking antibiotic B reference substance appropriate, use is dilute
Release agent dissolve and quantify dilution be made in every 1ml containing about the solution of 0.2mg antibiotic B；It prepares test solution: taking antibiotic A:
B (5:1) appropriate test sample, dissolved with diluent and quantify dilution be made in every 1ml it is (anti-containing about 0.2mg containing about 1mg antibiotic A
Raw element B) solution；Prepare contrast solution: precision measures test solution 1ml, sets in 100ml measuring bottle, diluent is added to be diluted to
Scale simultaneously shakes up；
S3, blank solution, antibiotic A reference substance solution, antibiotic B reference substance solution, appropriate test solution are taken respectively
Sample introduction, chromatographic condition is as follows, chromatographic column: TSK-GEL G2000SWXL gel chromatographic columns (30cm × 7.8mm, 5 μm)；Mobile phase:
0.01mol/L phosphate buffer；Flow velocity: 1.0ml/min；Detection wavelength: 254nm；Sample volume: 10 μ l；Column temperature: 25 DEG C；Into
Sample dish temperature: 4 DEG C；Wherein mobile phase is made by following methods: 0.01mol/L sodium dihydrogen phosphate；0.01mol/L disodium hydrogen phosphate
(61: 39, V/V) adjusts pH to 7.0 with 5mol/L sodium hydroxide solution, records chromatogram, it is detailed in FIG. 1 to FIG. 4, reading numerical values
Complete detection；.By FIG. 1 to FIG. 4 it is found that main peak adjacent high-molecular polymer peak retention time is 9.19min, separated with main peak
Degree is 3.28；Blank solvent and other impurities do not interfere the measurement of high molecular polymer in this product.
Repeated experiment:
It is parallel to prepare 6 parts by the test solution and contrast solution preparation method of above-described embodiment, above-mentioned implementation is pressed respectively
The chromatographic condition sample introduction of example records chromatogram；And the average content for calculating polymer in 6 parts of test solutions is 0.71%, phase
It is 2.65% (n=6) to standard deviation (RSD), shows this method repeatability preferably；
Sample introduction Precision Experiment:
By the test solution and contrast solution preparation method of above-described embodiment, 1 part is prepared, respectively by by above-described embodiment
Chromatographic condition repeat 6 needle of sample introduction, record chromatogram；Calculate 6 sample introductions of test solution map in polymer peak area and
Relative standard deviation (RSD) be 0.30% (n=6), the relative standard of main peak peak area in the map of 6 sample introductions of contrast solution
Deviation (RSD) is 0.11% (n=6), shows that this method sample introduction precision is preferable.
Intermediate precision experiment:
Personnel, date and instrument are replaced simultaneously, by the test solution and contrast solution preparation method of above-described embodiment, is put down
Row prepares 6 parts, presses the chromatographic condition sample introduction of above-described embodiment respectively, records chromatogram.Calculate polymer in 6 parts of test solutions
Average content be 0.74%, relative standard deviation (RSD) be 3.66% (n=6), with repeated result amount to relative standard it is inclined
Poor (RSD) is 3.90% (n=12), shows that this method Intermediate precision is preferable.
Study on the stability experiment:
By the test solution and contrast solution preparation method of above-described embodiment, 1 part is prepared, is transferred respectively at 4 DEG C of conditions
By the chromatographic condition sample introduction of above-described embodiment when setting 0,2,4,8,12,24,64, chromatogram is recorded；Test solution is in 4 DEG C of conditions
Lower placement 64h does not generate the unknown polymer in reporting limit, and each polymer peak area known loses apparent increase and becomes
Gesture, the RSD% of polymer peak area sum is 1.06% between each time point, and test solution is in 64h cohesion under the conditions of this shows 4 DEG C
It is with good stability to close object.Contrast solution places 64h under the conditions of 4 DEG C, and the RSD% of main peak peak area is between each time point
1.53%, contrast solution is with good stability in 64h under the conditions of this shows 4 DEG C.
Detection limit, quantitative limit investigate experiment:
Take the antibiotic A reference substance solution of above-described embodiment appropriate, after adding diluent to dilute step by step, by above-described embodiment
Chromatographic condition sample introduction, calculates quantifying for antibiotic A with signal-to-noise ratio > 10 and is limited to 1.2ng, calculates antibiotic A's with signal-to-noise ratio > 3
Detection is limited to 0.6ng.
It is linear to investigate experiment:
It takes the test solution of above-described embodiment appropriate, adds 0.1M sodium hydroxide solution to carry out alkali destruction, with 0.1M hydrochloric acid
Solution presses the chromatographic condition sample introduction of above-described embodiment after neutralizing, record chromatogram, calculates polymer content about by Self-control method
As linear stock solution when being 5%, precision pipette linear stock solution 0.1ml, 0.2ml, 0.4ml, 1.0ml, 2.0ml, 2.5ml,
3.3ml, 4ml are set respectively in 8 10ml volumetric flasks, with diluent constant volume.Respectively by 5.2.1 lower chromatographic condition sample introductions, record
Chromatogram.It is that ordinate carries out linear regression using polymer content as abscissa, peak area (y), obtains polymeric linear recurrence side
Journey y=9.8464x-0.0166 (r=0.9999)；By Fig. 5 linear graph the result shows that, polymer content is 0.05%~5%
With its peak area in good linear relationship in range；
Durability investigates experiment:
By the test solution and contrast solution preparation method of above-described embodiment, 1 part is prepared, investigates use different columns respectively
The influence of temperature, flow velocity, pH, mobile phase salinity to high molecular polymer assay in antibiotic A:B (5:1), the results are shown in Table
1.As shown in Table 1, above-mentioned factor change in a certain range between high molecular polymer peak and high molecular polymer peak with
Separating degree between main peak influences less, to meet the requirement of version " Chinese Pharmacopoeia " (four) annex 0512HPLC method in 2015,
Illustrate the good tolerance of this method.
Table 1- durability result summarizes
Since the high molecular polymer in antibiotic is the main reason for generating allergic reaction, control beta-lactam is anti-
High molecular polymer content in raw element, it is ensured that clinical application it is safe and effective.Foreign pharmacopeia there is no effective control at present
The detection means of macromolecule impurity.It is high in the External standard method quantitative determination beta-lactam antibiotic that Chinese Pharmacopoeia records
The detection method of polymers replaces the confrontation of macromolecule impurity reference substance by the conversion of two kinds of mobile phases with drug own control product
High polymer in raw element is detected, solve the problems, such as to a certain extent it is external insurmountable, but aforesaid way disadvantage compared with
It is more, and the present invention compensates for above-mentioned deficiency, overcomes above-mentioned many difficult points, the high polymer measurement being more suitable in antibiotic,
Have the advantages that easy to operate, specificity is strong, high sensitivity；
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, although referring to aforementioned reality
Applying example, invention is explained in detail, for those skilled in the art, still can be to aforementioned each implementation
Technical solution documented by example is modified or equivalent replacement of some of the technical features.It is all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (3)
1. the detection method of polymer in a kind of measurement cephalosporin analog antibiotic, it is characterised in that: its step are as follows,
S1, purified water is placed 2-8 DEG C of refrigerator, takes out diluent, that is, blank solution is made before use
S2, it prepares antibiotic A reference substance solution: taking antibiotic A reference substance appropriate, dissolved with diluent and quantify dilution and be made often
Containing about the solution of 1mg antibiotic A in 1ml；
It prepares antibiotic B reference substance solution: taking antibiotic B reference substance appropriate, dissolved with diluent and quantify dilution every 1ml is made
In solution containing about 0.2mg antibiotic B；
It prepares test solution: taking antibiotic A:B (5:1) appropriate test sample, dissolved with diluent and quantify dilution every 1ml is made
In solution containing about 1mg antibiotic A (containing about 0.2mg antibiotic B)；
Prepare contrast solution: precision measures test solution 1ml, sets in 100ml measuring bottle, adds diluent to be diluted to scale and shake
It is even；
S3, blank solution, antibiotic A reference substance solution, antibiotic B reference substance solution, the appropriate sample introduction of test solution are taken respectively,
Chromatogram is recorded, reading numerical values complete detection.
2. the detection method of polymer in a kind of measurement cephalosporin analog antibiotic according to claim 1, it is characterised in that: color
Spectral condition is as follows, chromatographic column: TSK-GEL G2000SWXL gel chromatographic columns (30cm × 7.8mm, 5 μm)；Mobile phase:
0.01mol/L phosphate buffer；Flow velocity: 1.0ml/min；Detection wavelength: 254nm；Sample volume: 10 μ l；Column temperature: 25 DEG C；Into
Sample dish temperature: 4 DEG C.
3. the detection method of polymer in a kind of measurement cephalosporin analog antibiotic according to claim 2, it is characterised in that: stream
It is dynamic to be mutually made by following methods: 0.01mol/L sodium dihydrogen phosphate；0.01mol/L disodium hydrogen phosphate (61: 39, V/V), uses 5mol/
L sodium hydroxide solution adjusts pH to 7.0.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910718620.1A CN110361475A (en) | 2019-08-05 | 2019-08-05 | The detection method of polymer in a kind of measurement cephalosporin analog antibiotic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910718620.1A CN110361475A (en) | 2019-08-05 | 2019-08-05 | The detection method of polymer in a kind of measurement cephalosporin analog antibiotic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110361475A true CN110361475A (en) | 2019-10-22 |
Family
ID=68223245
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910718620.1A Pending CN110361475A (en) | 2019-08-05 | 2019-08-05 | The detection method of polymer in a kind of measurement cephalosporin analog antibiotic |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110361475A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111948318A (en) * | 2020-08-16 | 2020-11-17 | 江苏正大清江制药有限公司 | Method for determining high-molecular polymer in cefuroxime axetil tablets |
| CN112034057A (en) * | 2020-08-16 | 2020-12-04 | 江苏正大清江制药有限公司 | Method for determining high-molecular polymer in cefuroxime axetil raw material |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104165949A (en) * | 2014-08-29 | 2014-11-26 | 四川制药制剂有限公司 | Inspection method for cefodizime sodium polymer for injection |
| CN104458984A (en) * | 2014-10-14 | 2015-03-25 | 天津医药集团津康制药有限公司 | Method for determining polymer in cephalosporins drug |
| CN107576735A (en) * | 2017-07-18 | 2018-01-12 | 江苏正大清江制药有限公司 | A kind of method of high molecular polymer in measure Faropenem sodium |
| CN108020623A (en) * | 2017-12-30 | 2018-05-11 | 国药集团致君（深圳）制药有限公司 | The content assaying method of polymer in cephalosporin analog antibiotic medicine |
-
2019
- 2019-08-05 CN CN201910718620.1A patent/CN110361475A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104165949A (en) * | 2014-08-29 | 2014-11-26 | 四川制药制剂有限公司 | Inspection method for cefodizime sodium polymer for injection |
| CN104458984A (en) * | 2014-10-14 | 2015-03-25 | 天津医药集团津康制药有限公司 | Method for determining polymer in cephalosporins drug |
| CN107576735A (en) * | 2017-07-18 | 2018-01-12 | 江苏正大清江制药有限公司 | A kind of method of high molecular polymer in measure Faropenem sodium |
| CN108020623A (en) * | 2017-12-30 | 2018-05-11 | 国药集团致君（深圳）制药有限公司 | The content assaying method of polymer in cephalosporin analog antibiotic medicine |
Non-Patent Citations (1)
| Title |
|---|
| 姚蕾等: "注射用头孢唑肟钠的高分子聚合物检查方法的建立与验证", 《药品评价》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111948318A (en) * | 2020-08-16 | 2020-11-17 | 江苏正大清江制药有限公司 | Method for determining high-molecular polymer in cefuroxime axetil tablets |
| CN112034057A (en) * | 2020-08-16 | 2020-12-04 | 江苏正大清江制药有限公司 | Method for determining high-molecular polymer in cefuroxime axetil raw material |
| CN111948318B (en) * | 2020-08-16 | 2022-04-01 | 江苏正大清江制药有限公司 | Method for determining high-molecular polymer in cefuroxime axetil tablets |
| CN112034057B (en) * | 2020-08-16 | 2022-04-01 | 江苏正大清江制药有限公司 | Method for determining high-molecular polymer in cefuroxime axetil raw material |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104655751B (en) | A kind of detect the method for organic solvent residual in dapoxetine | |
| CN109870521B (en) | Method for separating oseltamivir phosphate enantiomers by normal phase chromatography | |
| CN110361475A (en) | The detection method of polymer in a kind of measurement cephalosporin analog antibiotic | |
| CN110398548A (en) | The high performance liquid chromatography separation measuring method and application of relative substance in a kind of fosfomycin trometamol bulk pharmaceutical chemicals and its preparation | |
| CN110146621B (en) | Method for determining content of polymer in cephalosporin antibiotic medicine | |
| CN108020623A (en) | The content assaying method of polymer in cephalosporin analog antibiotic medicine | |
| CN101008637B (en) | Quality control method of fasudil hydrochloride injection | |
| CN108663448A (en) | Detection method in relation to substance in a kind of Amino Acid Compound Injection | |
| CN104597171A (en) | High performance liquid chromatography analysis method of acarbose and its preparation | |
| CN101685085B (en) | Method for analyzing high performance liquid chromatography of methanesulfonic amine ginkgolide B | |
| CN104458984A (en) | Method for determining polymer in cephalosporins drug | |
| CN109613128A (en) | The measuring method of drug content in a kind of Famotidine Capsule | |
| CN106124684A (en) | A kind of qualitative and quantitative detection method of Pericarpium Granati ZHIXIE SAN | |
| CN105424834B (en) | Detect 2-Pyrrolidone and formic acid method in PVP K30 simultaneously | |
| CN104950047A (en) | Method for detecting content, dissolution rate and releasing rate of memantine hydrochloride or analogues thereof in medicinal agent | |
| CN114965761B (en) | Detection method of N-hydroxysuccinimide in polyethylene glycol protein medicine | |
| CN109580834A (en) | Detection method in relation to substance in a kind of pharmaceutical preparation containing C14H25N4NaO11P2 | |
| CN111307957A (en) | Method for detecting tween 80 content in pharmaceutical preparation | |
| CN103323541B (en) | Quality detection method for heparin sodium tube-enveloping injection | |
| Varaprasad et al. | Method development and validation of phenytoin sodium in bulk and its pharmaceutical dosage form by RP-HPLC method | |
| CN102928525A (en) | Method for detecting related substance II of cefpirome in cefpirome sulfate/sodium chloride injection | |
| CN108872406A (en) | HPLC analyzing detecting method in relation to substance in a kind of L-aminobutanedioic acid bulk pharmaceutical chemicals | |
| CN105572063A (en) | Isocarbophos convenient detection method based on hemin controllable aggregation | |
| Flood et al. | Urinary metanephrines as measured by liquid chromatography with an on-line post-column reaction detector. | |
| CN114518413A (en) | Method for measuring content of proline in captopril raw material medicine |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20191022 |
|
| RJ01 | Rejection of invention patent application after publication |