CN107576735A - A kind of method of high molecular polymer in measure Faropenem sodium - Google Patents
A kind of method of high molecular polymer in measure Faropenem sodium Download PDFInfo
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- CN107576735A CN107576735A CN201710584261.6A CN201710584261A CN107576735A CN 107576735 A CN107576735 A CN 107576735A CN 201710584261 A CN201710584261 A CN 201710584261A CN 107576735 A CN107576735 A CN 107576735A
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Abstract
The invention discloses a kind of detection method of high molecular polymer in gel chromatography faropenem sodium raw materials, it comprises the following steps：The chromatographic column of high performance liquid chromatograph is the chromatographic column that Aquapak A-440 is filler, and mobile phase is the cushioning liquid methanol of 0.1mol/L pH=6.8 7.2, and detector is UV-detector, and the 224nm of Detection wavelength 220, flow velocity is 0.4 0.6ml/min.Each 20 μ l injections high performance liquid chromatograph of reference substance solution, need testing solution, blank solution is drawn, records chromatogram.The value for calculating reference substance solution concentration is X and corresponding peak area value is Y, carry out linear fit, draw equation of linear regression, the present invention applies the content of Faropenem sodium high molecular polymer in Aquapak A-440 chromatography determination Faropenem sodium bulk drug, separative efficiency is high, strong antijamming capability, analyze speed is fast, detection sensitivity is high, can more preferably control the quality of Faropenem sodium bulk drug.
Description
Technical field
The present invention relates to analysis technical field, and in particular to a kind of detection for determining high molecular polymer in Faropenem sodium
Method.
Background technology
Faropenem sodium is developed by Japanese Suntory companies, in a kind of penems antibiotics of listing in 1997, tool
There are has a broad antifungal spectrum, antibacterial activity strong.It is stable to beta-lactamase, to extended spectrumβ-lactamase producing strains, citrobacter, intestines
Coccus has the characteristics of good action, because Faropenem sodium easily produces high score among synthetic reaction and sample storage process
The polymer of son, the main reason for such polymer is penicillin anaphylaxis symptom is shown according to research, therefore both at home and abroad to β-interior
The control of the macromolecule impurity of amide-type antibiotic is paid much attention to, and is detected for this by rational means and is controlled this family macromolecule
Polymer has important practical significance.
The content of the invention
The purpose of the present invention is to establish a kind of detection method for determining high molecular polymer in Faropenem sodium, can be more preferable
Control Faropenem sodium bulk drug in faropenem high molecular polymer content, can more preferably control Faropenem sodium former
Expect the quality of medicine.
The technical scheme is that using Faropenem sodium macromolecule in gel chromatography faropenem bulk drug
Polymer, it comprises the following steps：
It is appropriate that faropenem reference substance is followed the example of in the preparation of reference substance solution, accurately weighed, with the buffer solution of 0.1mol/L pH=7.0
Every 1ml 0.01mg containing Faropenem sodium solution is made；
The preparation of need testing solution samples about product 10mg, accurately weighed, puts in 10ml measuring bottles, adds 0.1mol/LpH=7.0 to buffer
Liquid is diluted to scale and shaken up；
The preparation of blank solution：The buffer solution of 0.1mol/LpH=7.0；
Chromatographic column is：Aquapak A-440 TSKgel G2000SWxl chromatographic columns；
Chromatographic condition is：40 DEG C of column temperature, detector：UV-detector Detection wavelength 222nm；Flow velocity：0.5ml/min .
Mobile phase：0.1mol/L pH=7.0；Cushioning liquid：Methanol=95:5；
Sample introduction：Each 20 μ l of contrast solution, need testing solution, blank solution are taken, respectively sample introduction record chromatogram；
Calculate the equation of linear regression of value and the corresponding peak area value of standard solution concentration, coefficient correlation and should be not less than
0.99；Precision draws need testing solution 20 μ l injection liquid chromatograph, in need testing solution chromatogram, faropenem sodium polymer
Content must not exceed 0.15%, separating degree should be greater than 1.5 between faropenem sodium polymer and adjacent chromatographic peak.
Brief description of the drawings：Fig. 1 is the chromatogram that Faropenem sodium separates with polymer under different flow phase systems.
Form is described in further details to present disclosure again by the following examples, but not this should not be interpreted as with regard to this
Invent in above-mentioned subject area and be only limitted to following examples.It is general according to this area under the premise of the above-mentioned technology of the present invention is not departed from
The modification of corresponding replacement or change that logical technological know-how and customary means are made, is included in the present invention.
The selection of the chromatographic column of embodiment 1
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid
Chromatographic condition
Chromatographic column：G-10 10.0mm × 300mm sephadex chromatography posts
Detection wavelength：222nm, flow velocity：1.2ml/min, column temperature：35 DEG C, mobile phase：PH7.0 0.1mol/L phosphate-buffereds
Liquid, sample size：20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0
The preparation of test solution：Follow the example of that faropenem is appropriate, 1mg/ml solution is diluted to the cushioning liquid of pH=7.0,25
DEG C place 48 hours sample introductions.
Conclusion：Chromatographic peak hangover using the separation of the filler is serious, and Faropenem sodium can not separate with polymer.
The selection of the chromatographic column of embodiment 2
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid
Chromatographic condition
Chromatographic column：G-10 14.0mm × 400mm sephadex chromatography posts
Detection wavelength：222nm, flow velocity：1.2ml/min, column temperature：35 DEG C, mobile phase：PH7.0 0.1mol/L phosphate-buffereds
Liquid, sample size：20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0；
The preparation of test solution：Follow the example of that faropenem is appropriate, 1mg/ml solution is diluted to the cushioning liquid of pH=7.0,25
DEG C place 48 hours sample introductions.
Conclusion：Chromatographic peak hangover using the separation of the filler is serious, and Faropenem sodium is 1.2 with polymer separating degree,
Requirement of experiment can not be met.
The selection of the chromatographic column of embodiment 3
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid
Chromatographic condition
Chromatographic column：G2000SWxl （300mm）Aquapak A-440 chromatographic column
Detection wavelength：222nm, flow velocity：1.2ml/min, column temperature：35 DEG C, mobile phase：PH7.0 0.1mol/L phosphate-buffereds
Liquid, sample size：20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0；
The preparation of test solution：Follow the example of that faropenem is appropriate, 1mg/ml solution is diluted to the cushioning liquid of pH=7.0,25
DEG C place 48 hours sample introductions.
Conclusion：Using the chromatographic column of the filler, Faropenem sodium peak shape is symmetrical.
The selection and optimization of the chromatographic condition of embodiment 4
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid, ammonium acetate
Chromatographic condition
Chromatographic column：G2000SWxl （300mm）Aquapak A-440 chromatographic column
Detection wavelength：222nm, flow velocity：0.5ml/min, column temperature：35 DEG C, mobile phase：PH7.0 0.1mol/L phosphate-buffereds
Liquid, sample size：20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0：Methanol=95:5；
The preparation of test solution：Follow the example of that faropenem is appropriate, 1mg/ml solution is diluted to the cushioning liquid of pH=7.0,25
DEG C place 48 hours sample introductions.
Analyzed respectively with four kinds of mobile phases in table 1, chromatogram as shown in figure 1, with Faropenem sodium principal component with
It is inspection target that it, which detects high molecular polymer separating degree and bulk analysis time,.
Table 1 is used for the different flowing phase compositions for optimizing chromatographic isolation
| Numbering | Flow phase composition | Separating degree | Analysis time（min） |
| a | 0.1mol/L pH=7.0 cushioning liquid-methanol（95：5） | 1.74 | 30 |
| b | 0.1mol/L pH=7.0 cushioning liquid-methanol（90：10） | 1.56 | 30 |
| c | 0.1mol/L pH=7.0 cushioning liquid-methanol-acetonitrile（90：5：5） | 1.68 | 30 |
| d | 0.1mol/L pH=7.0 cushioning liquid-acetonitrile（95：5） | 1.68 | 30 |
| e | 0.1mol/L pH=7.0 cushioning liquid-acetonitrile（90：10） | 1.44 | 30 |
Conclusion：It was found that in above-mentioned five kinds of chromatographic systems, 0.1mol/L pH=7.0 cushioning liquid-methanol（95：5）, as mobile phase
When, indices are optimal.
The influence of the flow velocity of embodiment 5
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid, ammonium acetate
Chromatographic condition
Chromatographic column：G2000SWxl （300mm）Aquapak A-440 chromatographic column
Detection wavelength：220nm, column temperature：40 DEG C, mobile phase：PH7.0 0.1mol/L phosphate buffers, sample size：20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0：Methanol=95:5；
The preparation of test solution：Follow the example of that faropenem is appropriate, 1mg/ml solution is diluted to the cushioning liquid of pH=7.0,25
DEG C place 48 hours sample introductions.Flow velocity is respectively：0.5ml/min、1ml/min
Conclusion：As a result when to show flow velocity be 1.0ml/min, high molecular polymer can not effectively divide with principal component analysis faropenem peak
From when flow velocity is reduced to 0.5ml/min, the separating degree at each peak is good.
The influence of the column temperature of embodiment 6
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid, ammonium acetate
Chromatographic condition
Chromatographic column：G2000SWxl （300mm）Aquapak A-440 chromatographic column
Detection wavelength：220nm, flow velocity：0.5ml/min, mobile phase：PH7.0 0.1mol/L phosphate buffers, sample size：
20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0：Methanol=95:5；
The preparation of test solution：Follow the example of that faropenem is appropriate, 1mg/ml solution is diluted to the cushioning liquid of pH=7.0,25
DEG C place 48 hours sample introductions.Column temperature is respectively：25 DEG C, 35 DEG C, 50 DEG C the results are shown in Table 2.
Influence of the 2 different column temperatures of table to high molecular polymer separating degree
| Column temperature | The retention time of polymer | Main peak retention time | Main peak tailing factor | Separating degree |
| 25℃ | 21.98 | 24.82 | 1.35 | 2.03 |
| 35℃ | 21.68 | 24.36 | 1.29 | 2.12 |
| 50℃ | 21.36 | 23.52 | 1.54 | 1.96 |
Conclusion：As a result at 35 DEG C, principal component and the separating effect and symmetry of impurity cutting edge of a knife or a sword are optimal.
The specificity of embodiment 7
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps, water-bath, lighting box
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid, ammonium acetate, hydrochloric acid, sodium hydroxide
Chromatographic condition
Chromatographic column：G2000SWxl （300mm）Aquapak A-440 chromatographic column
Detection wavelength：220nm, column temperature：35 DEG C, flow velocity：0.5ml/min mobile phases：PH7.0 0.1mol/L phosphate-buffereds
Liquid, sample size：20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0：Methanol=95:5；
It is appropriate to follow the example of faropenem raw material, respectively through strong acid (0.1mol/L HCl) water-bath, highly basic (0.1mol/L NaOH) water
Bath, heating destruction processing, illumination, the need testing solution containing 0.2mg in every 1 milliliter is diluted to mobile phase respectively after neutralization.Take
1 above-mentioned solution is separated.
Conclusion：As a result show, under above-mentioned chromatographic system, various failure tests can increase polymer peak, be broken with alkali
Bad and acid destruction is the most obvious, and each peak separating degree is good.Solvent does not disturb the measure of Faropenem sodium and its macromolecule impurity.Table
The specificity of bright this method is good.
The sample introduction precision of embodiment 8 detects
Instrument and reagent
Instrument：Waters2998 detectors, Waters2695 solution transfer pumps,
Reagent：Water, potassium dihydrogen phosphate, phosphoric acid
Chromatographic condition
Chromatographic column：G2000SWxl （300mm）Aquapak A-440 chromatographic column
Detection wavelength：220nm, column temperature：35 DEG C, flow velocity：0.5ml/min mobile phases：PH7.0 0.1mol/L phosphate-buffereds
Liquid, sample size：20μl
Mobile phase：The cushioning liquid of 0.1mol/L pH=7.0：Methanol=95:5；
1mg/ml reference substance solution is taken, takes continuous sample introduction 6 times, surveys peak area, relative standard deviation RSD is 0.32%.
Conclusion：This method sample introduction precision is good.
The linear relationship of embodiment 9 is investigated：
For chromatographic condition with embodiment 8, it is appropriate that precision weighs Faropenem sodium reference substance, is diluted with the buffer solution of 0.1mol/LpH=7.0
To be made in every 1ml containing Faropenem sodium be respectively 0.0005,0.001,0.002,0.005,0.01,0.02,0.05,0.1,0.2,
0.5th, 1 and 1.5mg reference substance solution, with the peak area of Faropenem sodium（A）To its concentration（C）Linear regression is carried out, obtains line
Property equation A=65099008.3C-100055.5 results show that Faropenem sodium is in 0.0002mg/ml ~ 1.5mg/ml concentration ranges
Interior and peak area is in good linear relation r=1.0000
The test limit of embodiment 10 and quantitative limit
For chromatographic condition with embodiment 8, precision measures Faropenem sodium reference substance in right amount with the buffer solution of 0.1mol/LpH=7.0,
Sample introduction 10ul after diluting step by step, test limit is used as by S/N=3, records chromatogram, minimal detectable concentration is about 0.2ug/ml, sensitive
Degree is good.
The sample of embodiment 11 determines
It is appropriate that chromatographic condition with the precision of embodiment 8 weighs Faropenem sodium sample powder, dilute with 0.1mol/LpH=7.0 buffer solutions
Release and solution of every 1ml containing about 1mg is made, 3 batches of sample measurement results are shown in Table 3.
The sample measurement result of table 3
| Lot number | Compare peak area | Impurity peak area | Impurity % |
| 160816 | 600657 | 9307 | 0.01 |
| 160817 | 596926 | 9293 | 0.01 |
| 160818 | 598834 | 8753 | 0.01 |
The durability detector wavelength of embodiment 12 changes
Detector wavelength is become and turned to embodiment 8 by chromatographic condition：Detector wavelength change 1：220nm, detector wavelength change
2：224nm, original detector wavelength are：222nm, test result are shown in Table 4.
The detector wavelength of table 4 changes test result contrast table
| Detector wavelength | 222nm | 220nm | 224nm |
| Separating degree | 2.12 | 2.18 | 2.10 |
Conclusion：By being determined under above-mentioned chromatographic condition, can reach required separating effect, it is seen that Detection wavelength 220nm~
Change does not influence on the separation of Faropenem sodium high molecular polymer in 224nm allowed bands.
The durability change in flow of embodiment 13
Change in flow is by chromatographic condition with embodiment 8：Change in flow 1：0.4ml/min, change in flow 2：0.6ml/min, original
Beginning flow velocity：0.5ml/min, test result are shown in Table 5.
The change in flow test result contrast table of table 5
| Flow velocity | 0.4ml/min | 0.6ml/min | 0.5ml/min |
| Separating degree | 2.31 | 1.98 | 2.12 |
Conclusion：By being determined under above-mentioned chromatographic condition, can reach required separating effect, it is seen that flow velocity 0.4ml/min~
Change does not influence on the separation of Faropenem sodium high molecular polymer in 0.6ml/min allowed bands.
The durability column temperature of embodiment 14 changes
Column temperature is become and turned to embodiment 8 by chromatographic condition：Column temperature change 1：35 DEG C, column temperature change:2：45 DEG C, original column temperature：40
DEG C, test result is shown in Table 6.
The column temperature of table 6 changes test result contrast table
| Column temperature | 35℃ | 45℃ | 40℃ |
| Separating degree | 2.12 | 2.10 | 2.12 |
Conclusion：By being determined under above-mentioned chromatographic condition, it can reach required separating effect, it is seen that column temperature permits at 55 DEG C~45 DEG C
Perhaps change does not influence on the separation of Faropenem sodium high molecular polymer in the range of.
Embodiment 15 flows phase change
Chromatographic condition is the same as embodiment 8, mobile phase 1：By 0.1mol/L sodium dihydrogen phosphates, the buffer solution of pH=7.0, it is by mobile phase
2：By 0.1mol/L potassium dihydrogen phosphates, the buffer solution of pH=7.0, is 3 by mobile phase：Buffered by 0.1mol ammonium acetates/LpH=7.0
Liquid, test result are shown in Table 7
Table 7 flows phase change test result contrast table
| Mobile phase | 0.1mol/L sodium dihydrogen phosphates | 0.1mol/L potassium dihydrogen phosphates | 0.1mol ammonium acetates |
| Separating degree | 2.12 | 2.15 | 2.11 |
Conclusion：It can be seen that the change of cushioning liquid does not influence on the separation of Faropenem sodium high molecular polymer.
The stability of solution of embodiment 16
Chromatographic condition is with embodiment 8, and precision weighs sample 50mg into 50ml volumetric flasks plus 0.1mol/LpH=7.0 buffer solutions are molten
Solution, is diluted to scale, shakes up, and room temperature is placed, and in 0,1,2,5,8,12,24 hour difference 10ul sample introduction, determines peak area.Method sieve
Train southern sodium high molecular polymer peak area and increase gradually increase with the time in 24 hours.It is 0 that room temperature, which places product behind 24 hours,
42 times of hour.Principal component peak area is shown in without significant change substantially
Conclusion：It can be seen that Faropenem sodium is unstable in the buffer solution of 0.1mol/LpH=7.0, macromolecule impurity is easily produced, therefore
Test sample will face with newly matching somebody with somebody.
Claims (4)
1. the detection method of Faropenem sodium high molecular polymer in Aquapak A-440 chromatography determination faropenem sodium raw materials,
It is characterized in that it comprises the following steps：
The preparation of reference substance solution：It is appropriate to follow the example of faropenem reference substance, it is accurately weighed, with the buffer solution system of 0.1mol/LpH=7.0
Into every 1ml 0.01mg containing Faropenem sodium solution；
The preparation of need testing solution：About product 10mg is sampled, it is accurately weighed, put in 10ml measuring bottles, add 0.1mol/LpH=7.0 to buffer
Liquid is diluted to scale and shaken up；
The preparation of blank solution：The buffer solution of 0.1mol/LpH=7.0；
Chromatographic column is：Aquapak A-440 TSKgel G2000SWxl（7.8×300mm 5um）Chromatographic column；
Chromatographic condition：Column temperature is 35-45 DEG C, detector：UV-detector；220 ~ 224nm of Detection wavelength；Flow velocity：0.4-
0.6ml/min；Mobile phase：0.1mol/L pH=6.8-7.2；Cushioning liquid：Methanol=97-93:3-7；
Under above-mentioned chromatographic condition, precision draws μ l of contrast solution 20, μ l of need testing solution 20, the μ l of blank solvent 20 injection liquid phases
Chromatograph, chromatogram is recorded, calculate the value of standard solution concentration and the equation of linear regression of corresponding peak area value, coefficient correlation
And 0.99 should be not less than;Precision draws need testing solution 20 μ l injection liquid chromatograph, in need testing solution chromatogram, Fa Luopei
The content of southern sodium polymer must not exceed 0.15%, and separating degree should be greater than between faropenem sodium polymer and adjacent chromatographic peak
1.5。
2. the detection method of Faropenem sodium high molecular polymer in the measure Faropenem sodium raw material described in claim 1, its
It is characterised by that this method comprises the following steps：
The preparation of reference substance solution：It is appropriate to follow the example of faropenem reference substance, it is accurately weighed, with the buffer solution system of 0.1mol/LpH=7.0
Into every 1ml 0.01mg containing Faropenem sodium solution；
The preparation of need testing solution：About product 10mg is sampled, it is accurately weighed, put in 10ml measuring bottles, add 0.1mol/LpH=7.0 to buffer
Liquid is diluted to scale and shaken up；
The preparation of blank solution：The buffer solution of 0.1mol/LpH=7.0；
Chromatographic column is：Aquapak A-440 TSKgel G2000SWxl（7.8×300mm 5um）Chromatographic column；
Chromatographic condition：Column temperature is 35 DEG C, detector：UV-detector；Detection wavelength 220nm；Flow velocity：0.4ml/min；Flowing
Phase：0.1mol/L pH=6.8；Cushioning liquid：Methanol=97:3；
Under above-mentioned chromatographic condition, precision draws μ l of contrast solution 20, μ l of need testing solution 20, the μ l of blank solvent 20 injection liquid phases
Chromatograph, chromatogram is recorded, calculate the value of standard solution concentration and the equation of linear regression of corresponding peak area value, coefficient correlation
And 0.99 should be not less than；Precision draws need testing solution 20 μ l injection liquid chromatograph, in need testing solution chromatogram, Fa Luopei
The content of southern sodium polymer must not exceed 0.15%, and separating degree should be greater than between faropenem sodium polymer and adjacent chromatographic peak
1.5。
3. the detection method of Faropenem sodium high molecular polymer in the measure Faropenem sodium raw material described in claim 1, its
It is characterised by that this method comprises the following steps：
The preparation of reference substance solution：It is appropriate to follow the example of faropenem reference substance, it is accurately weighed, with the buffer solution system of 0.1mol/LpH=7.0
Into every 1ml 0.01mg containing Faropenem sodium solution；
The preparation of need testing solution：About product 10mg is sampled, it is accurately weighed, put in 10ml measuring bottles, add 0.1mol/LpH=7.0 to buffer
Liquid is diluted to scale and shaken up；
The preparation of blank solution：The buffer solution of 0.1mol/LpH=7.0；
Chromatographic column is：Aquapak A-440 TSKgel G2000SWxl（7.8×300mm 5um）Chromatographic column；
Chromatographic condition：Column temperature is 45 DEG C, detector：UV-detector；Detection wavelength 224nm；Flow velocity：0.6ml/min；Flowing
Phase：0.1mol/L pH=7.2；Cushioning liquid：Methanol=93:7；
Under above-mentioned chromatographic condition, precision draws μ l of contrast solution 20, μ l of need testing solution 20, the μ l of blank solvent 20 injection liquid phases
Chromatograph, chromatogram is recorded, calculate the value of standard solution concentration and the equation of linear regression of corresponding peak area value, coefficient correlation
And 0.99 should be not less than；Precision draws need testing solution 20 μ l injection liquid chromatograph, in need testing solution chromatogram, Fa Luopei
The content of southern sodium polymer must not exceed 0.15%, and separating degree should be greater than between faropenem sodium polymer and adjacent chromatographic peak
1.5。
4. the detection method of Faropenem sodium high molecular polymer in the measure Faropenem sodium raw material described in claim 1, its
It is characterised by that this method comprises the following steps：
The preparation of reference substance solution：It is appropriate to follow the example of faropenem reference substance, it is accurately weighed, with the buffer solution system of 0.1mol/LpH=7.0
Into every 1ml 0.01mg containing Faropenem sodium solution；
The preparation of need testing solution：About product 10mg is sampled, it is accurately weighed, put in 10ml measuring bottles, add 0.1mol/LpH=7.0 to buffer
Liquid is diluted to scale and shaken up；
The preparation of blank solution：The buffer solution of 0.1mol/LpH=7.0；
Chromatographic column is：Aquapak A-440 TSKgel G2000SWxl（7.8×300mm 5um）Chromatographic column；
Chromatographic condition：Column temperature is 40 DEG C, detector：UV-detector；Detection wavelength 222nm；Flow velocity：0.5ml/min；Flowing
Phase：0.1mol/L pH=7.0；Cushioning liquid：Methanol=95:5；
Under above-mentioned chromatographic condition, precision draws μ l of contrast solution 20, μ l of need testing solution 20, the μ l of blank solvent 20 injection liquid phases
Chromatograph, chromatogram is recorded, calculate the value of standard solution concentration and the equation of linear regression of corresponding peak area value, coefficient correlation
And 0.99 should be not less than；Precision draws need testing solution 20 μ l injection liquid chromatograph, in need testing solution chromatogram, Fa Luopei
The content of southern sodium polymer must not exceed 0.15%, and separating degree should be greater than between faropenem sodium polymer and adjacent chromatographic peak
1.5。
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| CN114689705A (en) * | 2020-12-26 | 2022-07-01 | 鲁南制药集团股份有限公司 | Method for detecting high-molecular polymer in tebipenem pivoxil raw material |
| CN114460187A (en) * | 2021-12-31 | 2022-05-10 | 成都天台山制药有限公司 | Method for detecting polymer in polypeptide |
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