CN108693292A - A kind of detection method of amoxil capsule impurity - Google Patents
A kind of detection method of amoxil capsule impurity Download PDFInfo
- Publication number
- CN108693292A CN108693292A CN201810827305.8A CN201810827305A CN108693292A CN 108693292 A CN108693292 A CN 108693292A CN 201810827305 A CN201810827305 A CN 201810827305A CN 108693292 A CN108693292 A CN 108693292A
- Authority
- CN
- China
- Prior art keywords
- mobile phase
- impurity
- detection methods
- uplc
- acetonitrile
- 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
Abstract
The present invention provides a kind of UPLC detection methods of amoxil capsule impurity, the UPLC detection methods select 230nm for Detection wavelength, using mixture of acetonitrile-phosphate buffer as mobile phase, gradient elution can detect impurity A in amoxil capsule, B, C, D, E, F, G, H, I, J and M simultaneously.Under this chromatographic condition, the impurity that cannot be efficiently separated with general analysis method can be efficiently separated, and specificity is good, high sensitivity, and analysis time is short, has saved a large amount of organic solvents.A kind of completely new selection is provided for amoxil capsule checked for impurities, control product quality.
Description
Technical field
The present invention relates to Pharmaceutical Analysis fields, specifically, the present invention relates to a kind of UPLC of amoxil capsule impurity
Detection method.
Background technology
Amoxicillin is that WHO recommends as preferred beta-lactam oral antibiotic, and bactericidal effect is strong, penetration cell
The ability of film is also strong, has stronger killing effect to Gram-negative bacteria and gram-positive bacteria, is clinically widely used in
The treatment of the infection such as respiratory system, urinary system, digestive system, ear-nose-throat department, gynemetrics, venereal disease, dept. of dermatology.Make Amoxicillin
It requires content to be not less than 98.5% when being used for drug, and stringent limitation is made that impurity content therein.
The major impurity that Amoxicillin is currently known is A, B, C, D, E, F, G, H, I, J, L, M, comes from synthesis material, tears open
Divide reagent, intermediate and catabolite (according to the difference of synthetic route, impurity is not exactly the same), structural formula is as follows:
"Chinese Pharmacopoeia (2015 editions)"The detection method of Wymox impurity is not recorded.To Amoxicillin raw material impurity
The detection method used for:Detection wavelength 254nm, flow velocity 1.0mL/min.With 0.05mol/L phosphate buffer (pH value
5.0)-acetonitrile (99:1) it is mobile phase A, 0.05mol/L phosphate buffers (pH value 5.0)-acetonitrile (80:20) it is Mobile phase B,
Gradient elution.The elution program is:
First with A-B (92:8) according to the form below gradient elution after isocratic elution to Amoxicillin appearance:
| T(min) | A (%) | B (%) |
| 0 | 92 | 8 |
| 25 | 0 | 100 |
| 40 | 0 | 100 |
| 41 | 92 | 8 |
| 55 | 92 | 8 |
Another to have document report to detect the analysis of Amoxicillin raw material, Jiang Zhulian etc. (cut by Jiang Zhulian, Zhang Wei, Liu Lvye columns
Change Two way chromatograms desalination mass spectrometry identification Amoxicillin in the Shandong impurity chemical industry, 2015,44 (2) 59-62.) do not change Ah
Under the premise of Amdinocillin National Pharmacopeia standard method, online desalination technology is switched by column, analysis condition is enable to be compatible with mass spectrum
And 4 kinds of impurity in Amoxicillin is identified, wherein impurity 1, impurity 2 are speculated as impurity D, and impurity 4 is speculated as impurity J, but the party
Method can not detach above-mentioned 12 kinds of known impurities simultaneously.(Li Yonghong, Zhou Fangfang, Fu Luping wait .RP-HPLC methods simultaneously to Li Yonghong etc.
The content Zhengzhou University journal (medicine) of raw material, intermediate and product in the technique of measurement enzymatic clarification Amoxicillin,
2016,51 (4):455-458.) use RP-HPLC methods, using Gemini-NX-C18 as stationary phase, V (methanol): V (0.05mol/
L, the phosphate buffer that pH value is 5.6)=it is mobile phase, flow velocity 1.0mL/min, Detection wavelength 230nm, sample size at 10: 90
10 μ L, column temperature are 30 DEG C, and separation raw material 6-amino-penicillanic acid (6-APA), D-para hydroxybenzene glycine methyl ester (HPGM) are intermediate
Body D-pHPG (HPG) and Amoxicillin, this method are isocratic elution, can not also be detached simultaneously known to above-mentioned 12 kinds
Impurity.
Having document, (Hong Jianwen, Lee interest the lady in the moon, Wang Yan butterfly .HPLC methods measure the content of amoxicillin granule and related substance
ACAD J GCP, 2009,25 (1):42-45.) analysis method reported is:Detection wavelength 230nm, flow velocity 1.0mL/
Min, 30 DEG C of column temperature.With 0.05mol/L phosphate buffers (pH value 5.0)-acetonitrile (99:1) it is mobile phase A, 0.05mol/L phosphorus
Phthalate buffer (pH value 5.0)-acetonitrile (80:20) it is Mobile phase B, gradient elution.The elution program is:
First with A-B (92:8) according to the form below gradient elution after isocratic elution to Amoxicillin appearance:
However, above-mentioned detection method exists, separable obtained impurity is few, and partial impurities are not completely separable with solvent peak, and
It is big with duration, organic solvent consumption.
Using UPLC-TOF-MS/MS methods measurement, (Lei Yongsheng, Song Liming, Hao Yingkui wait the Amoxicillins raw material to Lei Yongsheng etc.
UPLC-TOF-MS-MS identification modern medicines in medicine in relation to substance and clinical, 2015,30 (1):24-27.) use UPLC-
TOF-MS/MS methods measure impurity in the bulk pharmaceutical chemicals of Amoxicillin, using ammonium acetate system as mobile phase;Volume flow 0.5mL/min;Inspection
Survey wavelength 254nm;30 DEG C of column temperature;10 μ L of sample size.Electron spray ionisation source;Positive ion detection;Capillary voltage 3.0kV;Ion
120 DEG C of source temperature;500 DEG C of atomization gas temperature;Atomization gas volume flow 700L/h;Taper hole gas volumetric flow 50L/h, it was found that 6
A impurity, corresponding is impurity D, impurity D, impurity D, impurity G, impurity E and the impurity J in European Pharmacopoeia.The method is complicated for operation,
And it is only capable of 4 kinds of impurity of separation.
Invention content
The purpose of the present invention is to provide a kind of UPLC detection methods of amoxil capsule, the UPLC detection methods with
Mixture of acetonitrile-phosphate buffer is mobile phase, gradient elution, can detect simultaneously impurity A in amoxil capsule, B, C, D, E, F,
G, H, I, J and M.
In one embodiment, with 0.05mol/L potassium phosphate buffers-acetonitrile (99:Be 1) mobile phase A,
0.05mol/L mixture of acetonitrile-phosphate buffer (78:22) it is Mobile phase B, gradient elution.
The elution program of UPLC detection is:First with mobile phase A-Mobile phase B volume ratio for 92:8 isocratic elutions, wait for Ah
After Amdinocillin peak elutes, by following procedure gradient elution:0-15min, mobile phase A:Mobile phase B volume ratio fades to 0:
100, gradient elution;15-18.5min mobile phase A:Mobile phase B volume ratio is 0:100, isocratic elution;18.5-19min flowing
Phase A:Mobile phase B volume ratio fades to 92:8, gradient elution;After 19min, mobile phase A:Mobile phase B volume ratio is 92:8 is isocratic
Elution.
In one embodiment, the pH of the mobile phase A of the UPLC detection methods and Mobile phase B intermediate ion to buffer solution
For 4.5-5.5.
In one embodiment, with ion pair buffer-acetonitrile (99:1) it is mobile phase A, ion pair buffer-acetonitrile
(78:22) it is Mobile phase B, gradient elution, flow velocity 0.1-0.6mL/min;Detection wavelength is 254nm, and column temperature is 20-40 DEG C,
Sample size 1-8 μ L.
In one embodiment, it takes amoxil capsule product to be tested quantitatively to be diluted with mobile phase and test solution is made,
According to the principal component Self-control method calculation formula of the correction up factor:Content=F of impurity × (A confessions/A to) × 1%, calculating obtains
Obtain the content of impurity;Wherein, F is the relative correction factor of impurity, and A supplies the peak area for test solution impurity, and A is to for control
Solution main peak peak area, the relative correction factor are the equation of linear regression of the slope and impurity of main composition equation of linear regression
Slope ratio.
The present invention chromatographic condition under, for cannot be efficiently separated with general analysis method in amoxil capsule 12
Kind of impurity can be efficiently separated, and specificity is good, high sensitivity, and analysis time is short, has saved a large amount of organic solvents, has subtracted
Environmental pollution is lacked.
Specific implementation mode
In order to make art technology field personnel more fully understand the technical solution in the application, below in conjunction with following knot
Closing embodiment, the invention will be further described, it is clear that and described embodiments are only a part of embodiments of the present application, without
It is whole embodiment.Based on the embodiment in the application, those of ordinary skill in the art are not before making creative work
The all other embodiment obtained is put, shall fall within the protection scope of the present application.
Embodiment one:Amoxil capsule analysis method one
Instrument:Waters Acquity UPLC systems, chromatographic column:Waters Acquity UPLC BEH C18 chromatographic columns
(50mm × 2.1mm, 1.7 μm)
Mobile phase A:0.05mol/L potassium phosphate buffers (pH 5.5):Acetonitrile (99:1)
Mobile phase B:0.05mol/L potassium phosphate buffers (pH 5.5):Acetonitrile (78:22)
Flow velocity:0.1ml/min
Sample size:2μl
Detection wavelength:254nm
Column temperature:25℃
Gradient elution:First with mobile phase A-Mobile phase B volume ratio for 92:8 isocratic elutions wait for that peak elution in Amoxicillin finishes
Afterwards, by following procedure gradient elution:0-15min, mobile phase A:Mobile phase B volume ratio fades to 0:100, gradient elution;15-
18.5min mobile phase A:Mobile phase B volume ratio is 0:100, isocratic elution;18.5-19min mobile phase A:Mobile phase B volume
Than fading to 92:8, gradient elution;After 19min, mobile phase A:Mobile phase B volume ratio is 92:8 isocratic elutions.
Embodiment two:Amoxil capsule analysis method two
Instrument, chromatographic column, Detection wavelength, gradient elution are the same as embodiment one.
Mobile phase A:0.05mol/L potassium phosphate buffers (pH 4.5):Acetonitrile (99:1)
Mobile phase B:0.05mol/L potassium phosphate buffers (pH 4.5):Acetonitrile (78:22)
Flow velocity:0.6ml/min
Sample size:4μl
Column temperature:40℃
Embodiment three:Amoxil capsule analysis method three
Instrument, chromatographic column, Detection wavelength, gradient elution are the same as embodiment one.
Mobile phase A:0.05mol/L potassium phosphate buffers (pH 5.0):Acetonitrile (99:1)
Mobile phase B:0.05mol/L potassium phosphate buffers (pH 5.0):Acetonitrile (78:22)
Flow velocity:0.7ml/min
Sample size:1μl
Column temperature:30℃
Example IV:Amoxil capsule analysis method four
Instrument, chromatographic column, Detection wavelength, gradient elution are the same as embodiment one.
Mobile phase A:0.05mol/L potassium phosphate buffers (pH 4.2):Acetonitrile (99:1)
Mobile phase B:0.05mol/L potassium phosphate buffers (pH 4.2):Acetonitrile (78:22)
Flow velocity:0.3ml/min
Sample size:2μl
Column temperature:35℃
Embodiment five:Amoxil capsule analysis method five
Instrument, chromatographic column, Detection wavelength, gradient elution are the same as embodiment one.
Mobile phase A:0.05mol/L potassium phosphate buffers (pH5.0):Acetonitrile (99:1)
Mobile phase B:0.05mol/L potassium phosphate buffers (pH 5.0):Acetonitrile (78:22)
Flow velocity:0.5ml/min
Sample size:8μl
Column temperature:20℃
Embodiment six:Amoxil capsule analysis method six
Instrument, chromatographic column, flow velocity, Detection wavelength, sample size, column temperature, gradient elution are the same as embodiment one.
Mobile phase A:0.005mol/L ammonium acetate buffers (pH5.0):Acetonitrile (99:1)
Mobile phase B:0.005mol/L ammonium acetate buffers (pH 5.0):Acetonitrile (78:22)
Embodiment seven:Amoxil capsule analysis method seven
Instrument, chromatographic column, mobile phase, flow velocity, sample size, column temperature, gradient elution are the same as embodiment one.
Detection wavelength:254nm
Embodiment eight:Amoxil capsule analysis method eight
Instrument, chromatographic column are the same as embodiment one.
Mobile phase A:0.005mol/L ammonium acetate buffers (pH5.0):Acetonitrile (99:1)
Mobile phase B:0.005mol/L ammonium acetate buffers (pH 5.0):Acetonitrile (80:20)
Flow velocity:0.5ml/min
Detection wavelength:254nm
Sample size:10μl
Column temperature:30℃
Gradient elution:0~3.64min, 0%~60%B;3.64~12.53min, 60%B;
12.53~13.09min, 60%~0%B;13.09~17min, 0%B
Embodiment nine:Amoxil capsule analysis method nine
Instrument:1260 type high performance liquid chromatographs of Aglient,
Chromatographic column:5 μ 4.6 × 250mm of 110A of Gemini C18,
Mobile phase A:0.05mol/L potassium phosphate buffers (pH 5.0):Acetonitrile (99:1)
Mobile phase B:0.05mol/L potassium phosphate buffers (pH 5.0):Acetonitrile (80:20)
Flow velocity:1.0ml/min
Detection wavelength:230nm
Sample size:20μl
Column temperature:25℃
Gradient elution:First with mobile phase A-Mobile phase B (92:8) isocratic elution is pressed after waiting for the elution of Amoxicillin peak
Following procedure gradient elution:0-35min, mobile phase A:Mobile phase B volume ratio fades to 0:100, gradient elution;35-45min,
Mobile phase A:Mobile phase B volume ratio is 0:100, isocratic elution;45-46min, mobile phase A:Mobile phase B volume ratio fades to 92:
8, carry out gradient elution;After 46min, mobile phase A:Mobile phase B volume ratio is 92:8 isocratic elutions.
1 distinct methods separating effect of table compares
Embodiment ten:The application study of amoxil capsule analysis method one
Test solution:Take amoxil capsule product to be tested appropriate (containing about Amoxicillin 50mg), it is accurately weighed, add flowing
Phase A makes dissolving, constant volume shake up, filtering.
Reference substance solution:Take Amoxicillin reference substance appropriate, it is accurately weighed, add mobile phase A to dissolve and quantify dilution and is made
Containing about the solution of 20 Amoxicillins μ g in per 1ml.
HPLC detections are carried out to test solution and reference substance solution respectively according to above-mentioned chromatographic condition, then with correction up
The principal component Self-control method calculation formula of the factor:Content=F of impurity × (A confessions/A to) × 1% is calculated and is obtained containing for impurity
Amount;
Wherein, F is the relative correction factor of impurity, and A supplies the peak area for test solution impurity, and A is to for contrast solution
Main peak peak area, the relative correction factor be main composition equation of linear regression slope and impurity equation of linear regression it is oblique
The ratio of rate.
The relative retention time and relative correction factor of each impurity are shown in Table 2.
The relative retention time and relative correction factor of 2 each impurity of table
1. the detection method system suitability detection
Take Amoxicillin system suitability reference substance appropriate, add mobile phase A to dissolve and dilute be made in every 1ml containing about
The solution of the Amoxicillins 2.0mg takes 2 μ l injection liquid chromatographs, in addition to retention time is different, the chromatogram and standard drawing of record
Spectrum is consistent.
2. the detection method specificity detection
Strong Degrading experiment is accelerated to being broken to test sample under high temperature, strong acid, highly basic, Strong oxdiative, high light conditions
It is bad, it is therefore an objective to by investigating the separation situation of the catabolite and main peak and known impurities of sample, to compare the production quantity of impurity
With the decrement of main composition, the efficiency and applicability of analysis and assessment method is carried out with this.DAD detectors are used simultaneously, carry out peak
Purity test:In collection of illustrative plates obtained by Degrading experiment, when the purity factor of main composition is more than threshold value, then the chromatographic peak can determine whether not
Including other impurity peaks, chromatography peak purity meets the requirements.This hair detection method specificity is strong.
3 specificity test result of table
| Degradation condition | Main peak | The purity factor | Purity threshold value | Material balance |
| Without degradation | 98.85 | 999.464 | 999.00 | 101% |
| 60℃10d | 98.80 | 999.553 | 999.00 | 99.0% |
| 1N hydrochloric acid 30min | 85.43 | 999.913 | 999.00 | 97.8% |
| 0.1N sodium hydroxides 10min | 93.69 | 999.002 | 999.00 | 98.5% |
| 3% hydrogen peroxide 10min | 80.21 | 999.628 | 999.00 | 94.8% |
| Illumination degrading (UV20h) | 99.06 | 999.202 | 999.00 | 99.4% |
| High humidity (RH75%10d) | 99.09 | 999.474 | 999.00 | 99.4% |
3. the detection of the detection method quantitative limit and detection limit
Using signal-to-noise ratio method, principal component and each impurity reference substance are taken, a certain concentration, sample introduction, observation letter are diluted to solvent
It makes an uproar than S/N, signal-to-noise ratio corresponding a concentration of quantitative limit when being 10, signal-to-noise ratio corresponding a concentration of detection limit when being 3.Amoxicillin
And each impurity quantitative limit and detection limit result summarize and are shown in Table 4.
4 quantitative limit of table and detection limit test result
In the data of quantitative limit, the related material sample signal-to-noise ratio of sample concentration 0.05% is equivalent to 10 or more, is protected
Detection can be quantified by demonstrate,proving in sample 0.05% or more related substance;In the data of detection limit, it is equivalent to sample concentration
0.02% impurity sample signal-to-noise ratio ensures that in sample 0.02% or more related substance can be detected 3 or more, it was demonstrated that
The sensitivity of the present invention is very high.
3. the detection method is linear and range detection
Table 5 is linear and range test result
As shown in Table 4, the range of linearity for inventing the detection method for each impurity meets at least in LOQ values
Standard in the range of~index 150%, and regression coefficient regression coefficient >0.999, it was demonstrated that be in good linear relationship.
4. the repeatability detection of the detection method
This product is taken, is repeated 6 times detection by above-mentioned detection method, there is verification method good precision, standard to require impurity
The sum of absolute deviation must not exceed the 50% of quality standard, the results are shown in Table 6.
6 repetitive test result of table
Multiple impurity peaks are detected in 6 determination samples, wherein impurity D and impurity J are maximum, the absolute deviation of the sum of impurity
It is 0.17%, is no more than 50% (2.5%) of quality standard limit, it was demonstrated that this method has good precision.
It should be understood that the present invention disclosed is not limited only to specific method, scheme and the substance of description, because these
It is alterable.It will also be understood that purpose of the terminology used here just for the sake of the specific embodiment scheme of description, rather than
It is intended to limit the scope of the invention, the scope of the present invention is limited solely by the attached claims.
Those skilled in the art, which will also be appreciated that or be able to confirm that, uses no more than routine experiment, institute herein
Many equivalents of the specific embodiment of the present invention stated.These equivalents are also contained in the attached claims.
Claims (7)
1. a kind of UPLC detection methods of amoxil capsule impurity, it is characterised in that:The UPLC detection methods are with phosphate
Buffer solution-acetonitrile be mobile phase, gradient elution, and can detect simultaneously impurity A in amoxil capsule, B, C, D, E, F, G,
H, I, J and M
2. UPLC detection methods according to claim 1, it is characterised in that:The UPLC detection methods are with 0.05mol/L
Potassium phosphate buffer-acetonitrile (99:1) it is mobile phase A, 0.05mol/L mixture of acetonitrile-phosphate buffer (78:22) it is flowing
Phase B, gradient elution.
3. UPLC detection methods according to claim 1, it is characterised in that:The elution program of UPLC detection is:First
With mobile phase A-Mobile phase B volume ratio for 92:8 isocratic elutions are washed after waiting for the elution of Amoxicillin peak by following procedure gradient
It is de-:0-15min, mobile phase A:Mobile phase B volume ratio fades to 0:100, gradient elution;15-18.5min mobile phase A:Flowing
Phase B volume ratios are 0:100, isocratic elution;18.5-19min mobile phase A:Mobile phase B volume ratio fades to 92:8, gradient is washed
It is de-;After 19min, mobile phase A:Mobile phase B volume ratio is 92:8 isocratic elutions.
4. UPLC detection methods according to claim 1, it is characterised in that:The phosphate buffer pH value is 4.5-
5.5。
5. UPLC detection methods according to claim 1, it is characterised in that:The Detection wavelength is 230nm.
6. UPLC detection methods according to claim 1, it is characterised in that:The flow velocity is 0.1-0.6mL/min, column temperature
It is 20-40 DEG C, sample size 1-8 μ L.
7. UPLC detection methods according to claim 1, it is characterised in that:Take amoxil capsule product to be tested with mobile phase
Test solution is made in quantitative dilution, according to the principal component Self-control method calculation formula of the correction up factor:Content=F of impurity
× (A confessions/A to) × 1% calculates the content for obtaining impurity;Wherein, F is the relative correction factor of impurity, and A supplies to be that test sample is molten
The peak area of liquid impurity, A is to for contrast solution main peak peak area, the relative correction factor is main composition equation of linear regression
The ratio of the slope of the equation of linear regression of slope and impurity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810827305.8A CN108693292A (en) | 2018-07-25 | 2018-07-25 | A kind of detection method of amoxil capsule impurity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810827305.8A CN108693292A (en) | 2018-07-25 | 2018-07-25 | A kind of detection method of amoxil capsule impurity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108693292A true CN108693292A (en) | 2018-10-23 |
Family
ID=63850802
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810827305.8A Pending CN108693292A (en) | 2018-07-25 | 2018-07-25 | A kind of detection method of amoxil capsule impurity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108693292A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110066250A (en) * | 2019-03-29 | 2019-07-30 | 石药集团中诺药业（石家庄）有限公司 | A kind of amoxil capsule impurity and its preparation and analysis method |
| CN112461954A (en) * | 2020-11-11 | 2021-03-09 | 广州市力鑫药业有限公司 | Impurity detection method for amoxicillin bulk drug |
| CN112858519A (en) * | 2021-01-29 | 2021-05-28 | 黑龙江全乐制药有限公司 | Detection method for related substances of amoxicillin potassium clavulanate granules |
| CN112986289A (en) * | 2021-02-02 | 2021-06-18 | 海南海力制药有限公司 | Consistency evaluation and detection method of amoxicillin capsules |
-
2018
- 2018-07-25 CN CN201810827305.8A patent/CN108693292A/en active Pending
Non-Patent Citations (5)
| Title |
|---|
| RANDHIR SINGH DAHIYA: "Synthesis and Characterization of Potential Impurities in Amoxicillin", 《INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES REVIEW AND RESEARCH》 * |
| 杨荣珍 等: "超快速液相测定注射用阿莫西林钠的聚合物及有关物质", 《第八届沈阳科学学术年会论文集》 * |
| 沈丹丹 等: "阿莫西林/克拉维酸钾干混悬剂有关物质测定方法的比较研究", 《中国抗生素杂志》 * |
| 英国药典委员会: "《英国药典2010年版》", 31 December 2009 * |
| 雷勇胜 等: "阿莫西林原料药中有关物质的UPLC-TOF-MS/MS鉴定", 《现代药物与临床》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110066250A (en) * | 2019-03-29 | 2019-07-30 | 石药集团中诺药业（石家庄）有限公司 | A kind of amoxil capsule impurity and its preparation and analysis method |
| CN112461954A (en) * | 2020-11-11 | 2021-03-09 | 广州市力鑫药业有限公司 | Impurity detection method for amoxicillin bulk drug |
| CN112461954B (en) * | 2020-11-11 | 2021-07-09 | 广州市力鑫药业有限公司 | Impurity detection method for amoxicillin bulk drug |
| CN112858519A (en) * | 2021-01-29 | 2021-05-28 | 黑龙江全乐制药有限公司 | Detection method for related substances of amoxicillin potassium clavulanate granules |
| CN112986289A (en) * | 2021-02-02 | 2021-06-18 | 海南海力制药有限公司 | Consistency evaluation and detection method of amoxicillin capsules |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108693292A (en) | A kind of detection method of amoxil capsule impurity | |
| WO2018107975A1 (en) | Dexrazoxane analysis method | |
| Le-Minh et al. | Determination of six sulfonamide antibiotics, two metabolites and trimethoprim in wastewater by isotope dilution liquid chromatography/tandem mass spectrometry | |
| Barclay et al. | Trace analysis of fluoxetine and its metabolite norfluoxetine. Part II: Enantioselective quantification and studies of matrix effects in raw and treated wastewater by solid phase extraction and liquid chromatography–tandem mass spectrometry | |
| Nicolich et al. | Food safety evaluation: Detection and confirmation of chloramphenicol in milk by high performance liquid chromatography-tandem mass spectrometry | |
| CN109580850A (en) | A kind of efficient liquid-phase chromatography method of separation and measurement Oseltamivir phosphate and its specific impurities | |
| Chepyala et al. | Development and validation of a high-performance liquid chromatography-fluorescence detection method for the accurate quantification of colistin in human plasma | |
| Koželj et al. | Simple validated LC–MS/MS method for the determination of atropine and scopolamine in plasma for clinical and forensic toxicological purposes | |
| CN108693293A (en) | The method for detecting impurity in amoxicillin granules | |
| CN110146621B (en) | Method for determining content of polymer in cephalosporin antibiotic medicine | |
| Bolandnazar et al. | Development and application of an HPLC method for erlotinib protein binding studies | |
| EP3954371A1 (en) | Anti-acetylcholinesterase active composition in caulis mahoniae and screening method therefor and application thereof | |
| Horňák et al. | High-throughput determination of dissolved free amino acids in unconcentrated freshwater by ion-pairing liquid chromatography and mass spectrometry | |
| CN107315059B (en) | The content assaying method of rifampin and its impurity in a kind of rifampicin capsules | |
| Liu et al. | Sensitive Determination of Four Polypeptide Antibiotic Residues in Milk Powder by High Performance Liquid Chromatography–Electrospray Tandem Mass Spectrometry | |
| Douša et al. | HILIC-MS determination of dimethylamine in the active pharmaceutical ingredients and in the dosage forms of metformin | |
| Wang et al. | Rapid and simultaneous determination of ten anti-tuberculosis drugs in human plasma by UPLC-MS/MS with applications in therapeutic drug monitoring | |
| Gikas et al. | Development and validation of a UPLC‐UV method for the determination of daptomycin in rabbit plasma | |
| Parise et al. | A high-performance liquid chromatography–mass spectrometry assay for quantitation of the tyrosine kinase inhibitor nilotinib in human plasma and serum | |
| Balaji et al. | Analytical RPHPLC method for development and validation of Pregabalin in bulk and the determination of Pregabalin in capsule dosage form | |
| CN104359993B (en) | A kind of detection method of ambrisentan related substance | |
| Pérez-Lozano et al. | Stability evaluation of amoxicillin in a solid premix veterinary formulation by monitoring the degradation products through a new HPLC analytical method | |
| Nagumo et al. | Rapid quantification of cyanamide by ultra-high-pressure liquid chromatography in fertilizer, soil or plant samples | |
| Mžik et al. | Differential adsorption of an analyte and its D4, D5 and 13C6 labeled analogues combined with instrument-specific carry-over issues: the Achilles' heel of ibrutinib TDM | |
| CN104991027B (en) | The method for reducing fixedness buffer salt content in LC MS testers |
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: 20181023 |
|
| RJ01 | Rejection of invention patent application after publication |