CN106404952A - Determination method for related substances of Bromfenac sodium eye drops - Google Patents
Determination method for related substances of Bromfenac sodium eye drops Download PDFInfo
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- 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
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract
Belonging to the technical field of drug detection, the invention in particular relates to a determination method for related substances of Bromfenac sodium eye drops. The determination method includes the specific steps of: adopting an octadecyl silane bonded silica gel column or Lycopodine N-oxide M bonded silica gel column, and taking a phosphate buffer solution-acetonitrile as the mobile phase to conduct gradient elution, and setting the detection wavelength at 250-280nm, the column temperature at 10-30DEG C, the flow rate at 0.8-3ml/min, and a sample size of 20-70 microliter. Compared with the prior art, the determination method for related substances of Bromfenac sodium eye drops provided by the invention realizes separation and analysis of Bromfenac sodium and its related substances, and has the characteristics of good separation degree, strong specificity and high sensitivity, and can quantitate the three known impurities by self-control method without correction factor. The determination method has important practical significance for the quality control of Bromfenac sodium eye drops.
Description
Technical field
The invention belongs to drug measurement techniques field, it particularly relates to arrive a kind of relevant material of sodium bromophenolate eye drops
Assay method.
Background technology
Bromfenac sodium is 2- amino -3- benzoylphenylacetic acids analog derivative, its structure and Ketoprofen and Diclofenac class
Seemingly, the synthesis of the prostanoid inflammatory mediator of cyclooxygenase mediation can be suppressed, be one of maximally effective cyclooxygenase-2 inhibitors,
There is strength anti-inflammatory analgesic action, action intensity is 10 times of other NSAIDs (NSAIDs).Pharmacological evaluation shows,
Bromfenac sodium has antiinflammatory action to the acute conjunctiva edema of the Rat Experimental caused by arachidonic acid, carrageenan；Almost complete
Aqueous humor protein concentration caused by laser irradiates after suppression rabbit puncture of anterior chamber increases.Japan ratified Senju company in 2000
Sodium bromophenolate eye drops list, trade name XibromTM, and specification is 5ml:5mg, is clinically used for outer eye and the inflammation of front eye
The symptomatic treatment of disease property disease：Blepharitis, conjunctivitis, strong film scorching (in inclusion, strong film is scorching), post-operation inflammatory etc..
Sodium bromophenolate eye drops, during placing, can produce degradation impurity, and affect the quality of product.These are miscellaneous
Matter is the relevant material in Control of drug quality, and the impurity controlling for sodium bromophenolate eye drops mainly has three：Impurity 1：2-
Amino -3- (4- bromobenzoyl base) benzoic acid, impurity 2：2- amino -3- (4- bromobenzoyl base) benzoyl formic acid, impurity
3：7- (4- bromobenzoyl base) indoline -2,3- diketone.To the relevant material producing with degraded, need in the formulation to carry out matter
Amount controls, and therefore, realizes separation and the analysis of the associated material of bromfenac sodium, for the quality control of sodium bromophenolate eye drops
System has important practical significance.
Content of the invention
For solving above-mentioned technical problem, the Bromfenac that the invention provides a kind of separating degree is good, specificity is strong, sensitivity is high
Sodium eye drops is about the assay method of material.
A kind of sodium bromophenolate eye drops of the present invention are about the assay method of material, described assay method concrete steps
For：Lycopodine M bonded silica gel column is aoxidized using octadecylsilane chemically bonded silica post or N-, with mixture of acetonitrile-phosphate buffer is
Mobile phase, carries out gradient elution, and Detection wavelength is 250-280nm, and column temperature is 10-30 DEG C, and flow velocity is 0.8-3ml/min, sample introduction
Measure as 20-70uL.
About the assay method of material, described column temperature is room temperature to a kind of sodium bromophenolate eye drops of the present invention；Described
Detection wavelength is 266nm；
About the assay method of material, described flow velocity is to adjust Bromfenac to a kind of sodium bromophenolate eye drops of the present invention
The appearance time of sodium is 18min；Described sample size is 60uL.
A kind of sodium bromophenolate eye drops of the present invention are about the assay method of material, described gradient：
| Time (minute) | Mobile phase A (%) | Mobile phase B |
| 0 | 100 | 0 |
| 20.1 | 100 | 0 |
| 60.1 | 10 | 90 |
| 60.2 | 100 | 0 |
| 80 | 100 | 0 |
Wherein said mobile phase A is phosphate buffer:Acetonitrile=75:25；Mobile phase B is phosphate buffer-second
Nitrile=30:70；Described phosphate buffer is to take diammonium hydrogen phosphate 2.64g, is dissolved in water and is diluted to 1000ml, is adjusted with phosphoric acid
Section pH value is to 7.3 gained.
A kind of sodium bromophenolate eye drops of the present invention aoxidize lycopodine M key about the assay method of material, described N-
Close silicagel column preparation process be：1) silica gel taking 20g activation is in 500mL there-necked flask, then measures 100mL toluene and 40mL
Gamma-aminopropyl-triethoxy-silane, oil bath at 120 DEG C, it is stirred at reflux 13h, after cooling, product uses toluene successively, and ethanol is washed
Wash suction filtration to exist to no jelly；24h is dried at 60 DEG C, cooling in drying box；2) add step in the single port bottle of 500mL
1) product, then sequentially adds the formalin of 120mL 35% and the acetic acid solution of 2mL, reaction 2h is stirred at room temperature, through no
After water-ethanol suction filtration, it is placed in standby in 500mL there-necked flask；Take N- oxidation lycopodine M 4g to be dissolved in the appropriate aqueous solution, adjust molten
The pH value of liquid, to 8.0, adds in above-mentioned there-necked flask, 60 DEG C of stirring lower reaction 10h；Treat product cool down, successively with a large amount of secondary waters,
Absolute ethanol washing suction filtration is limpid to filtrate；60 DEG C of freeze-day with constant temperature 6h, in dress brown bottle after cooling down in the drying box N- oxidation
Lycopodine M bonded silica gel；3) by N- oxidation lycopodine M bonded silica gel conventional dress post, obtain final product.
A kind of sodium bromophenolate eye drops of the present invention are about the assay method of material, described assay method concrete steps
For：
1) precision measures sodium bromophenolate eye drops 5ml, puts in 50ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, and makees
For need testing solution；Precision measures need testing solution 1ml, puts in 200ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, and makees
For contrast solution；
2) precision weighs bromfenac sodium hydrate reference substance 25mg, puts in 25ml measuring bottle, plus flowing phased soln being diluted to
Scale, makes the solution containing about anhydrous bromfenac sodium 0.93mg in every 1ml, shakes up, as reference substance solution stock solution；Separately accurate
Measure reference substance solution stock solution 1ml, put in 200ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, molten as reference substance
Liquid；
3) precision weighs PVP K30 reference substance 200mg, puts in 10ml measuring bottle, is dissolved in water and is diluted to scale, makes
In every 1ml, the solution containing 20mg, shakes up, precision measures 5ml, puts in 50ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, and makees
For blank solution；
4) precision measures reference substance solution, contrast solution, blank solution and each 60 μ l of need testing solution, is injected separately into liquid phase
Chromatograph, records chromatogram, other single contaminant peak areas are compared with contrast solution main peak area；In addition to the polymer, each miscellaneous
Mass peak area and compared with contrast solution main peak area；
5) computing formula
In formula：SKPeak area for PVP K30 in blank solution；
SXPeak area for peak corresponding with blank solution PVP K30 peak retention time in need testing solution；
SRightPeak area for reference substance solution；
CSampleSign concentration for need testing solution；CRightConcentration for reference substance solution；
WRightFor the weight of reference substance, mg；
1.076 is the conversion factor with anhydrous bromfenac sodium for the hydrate of bromfenac sodium.
In formula：SMiscellaneous、SRightIt is respectively the main peak area of other single impurity peak area and contrast solution；
SWithFor in addition to the polymer, the sum of each impurity peak area.
Compared with prior art, sodium bromophenolate eye drops of the present invention achieve Bromfenac about the assay method of material
The separation of the associated material of sodium and analysis, and separating degree is good, specificity is strong, sensitivity is high, can using not correction up because
The Self-control method of son carries out quantitation to these three known impurities.This assay method is for the quality control of sodium bromophenolate eye drops
Have important practical significance.
Specific embodiment
With reference to specific embodiment to sodium bromophenolate eye drops of the present invention about material assay method do into
One step explanation, but protection scope of the present invention is not limited to this.
Embodiment 1
Using the relevant material of liquid chromatography analysis sodium bromophenolate eye drops, lycopodine M bonded silica gel is aoxidized using N-
Post, with mixture of acetonitrile-phosphate buffer as mobile phase, carries out gradient elution, and Detection wavelength is 266nm, and flow velocity is to adjust Bromfenac
The appearance time of sodium is 18min, and column temperature is room temperature, and sample size is 60uL；Gradient program is specially：
| Time (minute) | Mobile phase A (%) | Mobile phase B |
| 0 | 100 | 0 |
| 20.1 | 100 | 0 |
| 60.1 | 10 | 90 |
| 60.2 | 100 | 0 |
| 80 | 100 | 0 |
Wherein said mobile phase A：Phosphate buffer (takes diammonium hydrogen phosphate 2.64g, is dissolved in water and is diluted to
1000ml, with phosphorus acid for adjusting pH value to 7.3)-acetonitrile (75:25)；Mobile phase B：Phosphate buffer (takes diammonium hydrogen phosphate
2.64g, is dissolved in water and is diluted to 1000ml, with phosphorus acid for adjusting pH value to 7.3)-acetonitrile (30:70).
The preparation process that described N- aoxidizes lycopodine M bonded silica gel column is：1) silica gel taking 20g activation is in tri- mouthfuls of 500mL
In bottle, then measure the gamma-aminopropyl-triethoxy-silane of 100mL toluene and 40mL, oil bath at 120 DEG C, it is stirred at reflux 13h, treat
After cooling, product uses toluene successively, and ethanol washing suction filtration exists to no jelly；24h is dried at 60 DEG C, cold in drying box
But；2) in the single port bottle of 500mL add step 1) product, then sequentially add formalin and the 2mL of 120mL 35%
Acetic acid solution, be stirred at room temperature reaction 2h, after absolute ethyl alcohol suction filtration, be placed in standby in 500mL there-necked flask；Take N- oxidation lycopod
Alkali M 4g is dissolved in the appropriate aqueous solution, and the pH value adjusting solution, to 8.0, adds in above-mentioned there-necked flask, reacts under 60 DEG C of stirrings
10h；Treat that product cools down, limpid to filtrate with a large amount of secondary waters, absolute ethanol washing suction filtration successively；60 DEG C of freeze-day with constant temperature 6h, in
N- oxidation lycopodine M bonded silica gel is obtained in dress brown bottle after cooling in drying box；3) will be conventional for N- oxidation lycopodine M bonded silica gel
Dress post, obtains final product.
Confirmatory test：
1. the selection of wavelength
Precision weighs impurity 1, impurity 2 and each about 10mg of impurity 3, puts in 100ml measuring bottle respectively, is all dissolved and dilute with acetonitrile
Release to scale, shake up, precision measures 1ml, put in 100ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, in 200～400nm
Carry out UV scanning, impurity 1, impurity 2 and impurity 3 have larger absorption at 266nm wavelength.
2. separate specificity test
Need testing solution：Precision weighs bromfenac sodium raw material about 10mg, puts in 100ml measuring bottle, plus mobile phase A dissolves and dilute
Release to scale, shake up, make the solution containing about 0.1mg in every 1ml, as need testing solution.
Contrast solution：Precision measures need testing solution 1ml, puts in 200ml measuring bottle, plus mobile phase A is diluted to scale, shakes
Even, as contrast solution.
Intermediate V solution：Precision weighs intermediate V about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to
Scale, shakes up, and makes the solution containing about 0.1mg in every 1ml, as intermediate V solution.
Impurity 1 solution：Precision weighs impurity 1 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, make the solution containing about 0.1mg in every 1ml, as impurity 1 solution.
Impurity 2 solution：Precision weighs impurity 2 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, make the solution containing about 0.1mg in every 1ml, as impurity 2 solution.
Impurity 3 solution：Precision weighs impurity 2 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, make the solution containing about 0.1mg in every 1ml, as impurity 3 solution.
Blank auxiliary solution：By the auxiliary material of recipe quantity, prepare blank auxiliary solution.
Mixed solution：Precision weighs bromfenac sodium raw material about 20mg, puts in 200ml measuring bottle, adds above-mentioned dirt solution each
1ml, plus mobile phase A dissolves and be diluted to scale, shakes up, makes in every 1ml containing about bromfenac sodium 0.1mg, each 0.5 μ g of impurity
Solution, as mixed solution.
Take contrast solution 60 μ l injection liquid chromatograph, adjustment flow velocity makes the retention time of bromfenac sodium hydrate be about 18
Minute, adjust detection sensitivity, the peak height making principal component chromatographic peak is the 20%～30% of full scale；Take blank auxiliary molten again
Liquid, impurity 1 solution, impurity 2 solution, impurity 3 solution, intermediate V solution, mixed solution and each 60 μ l of need testing solution are respectively
Injection liquid chromatograph, records chromatogram.Peak sequence is impurity 1, bromfenac sodium, impurity 2, impurity 3, intermediate V.Test
Result shows, and is compared using octadecylsilane chemically bonded silica post in the past, after N- oxidation lycopodine M bonded silica gel column,
Separate more preferably between each impurity peaks, solvent peak and auxiliary material peak do not affect the detection of main peak and impurity peaks, the ladder to mobile phase simultaneously
Degree elution requirement selectively requires relatively can be lower.
3. detection limit
(1) bromfenac sodium precision weighs bromfenac sodium about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to quarter
Degree, shakes up, accurate absorption 1ml, puts in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, more accurate absorption 1ml, puts
In 200ml measuring bottle, plus mobile phase A is diluted to scale, and the accurate 60 μ l that draw inject liquid chromatographs, it is seen that now
Signal to noise ratio (S/N) is about 3, and that is, under this chromatographic condition, the detection of bromfenac sodium is limited to 0.15ng, with respect in need testing solution
The quantitation of bromfenac sodium is limited to 0.0025%.
(2) impurity 1 precision weighs impurity 1 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, accurate absorption 1ml, put in 200ml measuring bottle, be diluted to scale with mobile phase A, shake up, more accurate absorption 1ml, put 25ml amount
In bottle, plus mobile phase A is diluted to scale, shakes up, more accurate absorption 2ml, puts in 10ml measuring bottle, plus mobile phase A is diluted to scale,
Shake up, the accurate 60 μ l that draw inject liquid chromatographs, record chromatogram, it is seen that now signal to noise ratio (S/N) is about 3,
I.e. under this chromatographic condition, the minimum detectable activity of impurity 1 is 0.24ng, with respect to the minimum inspection of bromfenac sodium in need testing solution
Rising limit is 0.004%.
(3) impurity 2 precision weighs impurity 2 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, accurate absorption 1ml, put in 200ml measuring bottle, be diluted to scale with mobile phase A, shake up, more accurate absorption 1ml, put 100ml amount
In bottle, plus mobile phase A is diluted to scale, shakes up, and the accurate 60 μ l that draw inject liquid chromatographs, record chromatogram, can from figure
Find out, now signal to noise ratio (S/N) is about 3, that is, under this chromatographic condition, the minimum detectable activity of impurity 2 is 0.24ng, with respect to confession
In test sample solution, the minimum detection of bromfenac sodium is limited to 0.004%.
(4) impurity 3 precision weighs impurity III about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, accurate absorption 1ml, put in 200ml measuring bottle, be diluted to scale with mobile phase A, shake up, more accurate absorption 1ml, put 100ml amount
In bottle, plus mobile phase A is diluted to scale, shakes up, and the accurate 60 μ l that draw inject liquid chromatographs, record chromatogram, can from figure
Find out, now signal to noise ratio (S/N) is about 3, that is, under this chromatographic condition, the minimum detectable activity of impurity 3 is 0.24ng, with respect to confession
In test sample solution, the minimum detection of bromfenac sodium is limited to 0.004%.
4. quantitative limit
(1) bromfenac sodium precision weighs bromfenac sodium about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to quarter
Degree, shakes up, accurate absorption 1ml, puts in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, more accurate absorption 1ml, puts
In 50ml measuring bottle, plus mobile phase A is diluted to scale, and the accurate 60 μ l that draw inject liquid chromatographs, it is seen that now believing
Make an uproar and be about 10 than (S/N), that is, under this chromatographic condition, the quantitation of bromfenac sodium is limited to 0.6ng, with respect to bromine in need testing solution
The quantitation of fragrant acid sodium is limited to 0.01%, and the standard deviation RSD that mensure liquid continuous sample introduction is 6 times is less than 2.0%.
(2) impurity 1 precision weighs impurity 1 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, accurate absorption 1ml, put in 200ml measuring bottle, be diluted to scale with mobile phase A, shake up, more accurate absorption 1ml, put 50ml amount
In bottle, plus mobile phase A is diluted to scale, and the accurate 60 μ l that draw inject liquid chromatographs, record chromatogram, now signal to noise ratio (S/
N) it is about 10, that is, under this chromatographic condition, the quantitation of impurity 1 is limited to 0.6ng, with respect to the determining of bromfenac sodium in need testing solution
Amount is limited to 0.01%, and the standard deviation RSD that mensure liquid continuous sample introduction is 6 times is less than 2.0%.
(3) impurity 2 precision weighs impurity 2 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, accurate absorption 1ml, put in 200ml measuring bottle, be diluted to scale with mobile phase A, shake up, more accurate absorption 1ml, put 50ml amount
In bottle, plus mobile phase A is diluted to scale, and the accurate 60 μ l that draw inject liquid chromatographs, record chromatogram, now signal to noise ratio (S/
N) it is about 10, that is, under this chromatographic condition, the quantitation of impurity 2 is limited to 0.6ng, with respect to the determining of bromfenac sodium in need testing solution
Amount is limited to 0.01%, and the standard deviation RSD that mensure liquid continuous sample introduction is 6 times is less than 2.0%.
(4) impurity 3 precision weighs impurity 3 about 10mg, puts in 100ml measuring bottle, plus acetonitrile dissolves and is diluted to scale, shakes
Even, accurate absorption 1ml, put in 200ml measuring bottle, be diluted to scale with mobile phase A, shake up, more accurate absorption 1ml, put 50ml amount
In bottle, plus mobile phase A is diluted to scale, and the accurate 60 μ l that draw inject liquid chromatographs, record chromatogram, now signal to noise ratio (S/
N) it is about 10, that is, under this chromatographic condition, the quantitation of impurity 3 is limited to 0.6ng, with respect to the determining of bromfenac sodium in need testing solution
Amount is limited to 0.01%, and the standard deviation RSD that mensure liquid continuous sample introduction is 6 times is less than 2.0%.
5. the mensure of impurity correction factor
Precision weighs bromfenac sodium reference substance, impurity 1, impurity 2 and each about 10mg of impurity 3, puts in 100ml measuring bottle respectively,
Dissolved with acetonitrile and be diluted to scale, shake up, each precision measures 1ml, put respectively in 200ml measuring bottle, with mobile phase A dissolving and dilute
Release to scale, shake up.
Precision takes each 60 μ l sample introductions of above-mentioned solution respectively, records chromatogram, same to method, measures six times respectively, concrete outcome is shown in
Following table.
From data above, impurity 1, impurity 2 and impurity 3 relative response factor all in the range of 0.9-1.1, so can
So that quantitation is carried out to these three known impurities using the Self-control method being not added with correction factor.
Claims (6)
1. a kind of sodium bromophenolate eye drops about the assay method of material it is characterised in that described assay method concretely comprises the following steps：
Lycopodine M bonded silica gel column is aoxidized using octadecylsilane chemically bonded silica post or N-, with mixture of acetonitrile-phosphate buffer for flowing
Phase, carries out gradient elution, and Detection wavelength is 250-280nm, and column temperature is 10-30 DEG C, and flow velocity is 0.8-3ml/min, and sample size is
20-70μL.
2. a kind of sodium bromophenolate eye drops according to claim 1 about the assay method of material it is characterised in that described
Column temperature is room temperature；Described Detection wavelength is 266nm.
3. a kind of sodium bromophenolate eye drops according to claim 1 about the assay method of material it is characterised in that described
Flow velocity is the appearance time of regulation bromfenac sodium is 18min；Described sample size is 60uL.
4. a kind of sodium bromophenolate eye drops according to claim 1 about the assay method of material it is characterised in that described
Gradient：
Wherein said mobile phase A is phosphate buffer:Acetonitrile=75:25；Mobile phase B be mixture of acetonitrile-phosphate buffer=
30:70；Described phosphate buffer is to take diammonium hydrogen phosphate 2.64g, is dissolved in water and is diluted to 1000ml, uses phosphorus acid for adjusting pH
It is worth to 7.3 gained.
5. a kind of sodium bromophenolate eye drops according to claim 1 about the assay method of material it is characterised in that institute
State N- aoxidize lycopodine M bonded silica gel column preparation process be：1) silica gel taking 20g activation is in 500mL there-necked flask, then measures
100mL toluene and the gamma-aminopropyl-triethoxy-silane of 40mL, oil bath at 120 DEG C, it is stirred at reflux 13h, after cooling, product
Use toluene successively, ethanol washing suction filtration exists to no jelly；24h is dried at 60 DEG C, cooling in drying box；2) in 500mL
Single port bottle in add step 1) product, then sequentially add the formalin of 120mL 35% and the acetic acid solution of 2mL, room
Warm stirring reaction 2h, after absolute ethyl alcohol suction filtration, is placed in standby in 500mL there-necked flask；N- oxidation lycopodine M 4g is taken to be dissolved in suitable
In the amount aqueous solution, the pH value adjusting solution, to 8.0, adds in above-mentioned there-necked flask, reacts 10h under 60 DEG C of stirrings；Treat that product cools down,
Limpid to filtrate with a large amount of secondary waters, absolute ethanol washing suction filtration successively；60 DEG C of freeze-day with constant temperature 6h, fill after cooling down in the drying box
In brown bottle, obtain N- oxidation lycopodine M bonded silica gel；3) by N- oxidation lycopodine M bonded silica gel conventional dress post, obtain final product.
6. a kind of sodium bromophenolate eye drops according to claim 1 about the assay method of material it is characterised in that described
Assay method concretely comprises the following steps：
1) precision measures sodium bromophenolate eye drops 5ml, puts in 50ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, as confession
Test sample solution；Precision measures need testing solution 1ml, puts in 200ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, as right
According to solution；
2) precision weighs bromfenac sodium hydrate reference substance 25mg, puts in 25ml measuring bottle, plus the phased soln be diluted to scale of flowing,
Make the solution containing about anhydrous bromfenac sodium 0.93mg in every 1ml, shake up, as reference substance solution stock solution；Separately precision measures
Reference substance solution stock solution 1ml, puts in 200ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, as reference substance solution；
3) precision weighs PVP K30 reference substance 200mg, puts in 10ml measuring bottle, is dissolved in water and is diluted to scale, makes every
Contain the solution of 20mg in 1ml, shake up, precision measures 5ml, put in 50ml measuring bottle, plus mobile phase A is diluted to scale, shakes up, as
Blank solution；
4) precision measures reference substance solution, contrast solution, blank solution and each 60 μ l of need testing solution, is injected separately into liquid chromatogram
Instrument, records chromatogram, other single contaminant peak areas are compared with contrast solution main peak area；In addition to the polymer, each impurity peaks
Area and compared with contrast solution main peak area.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110687229A (en) * | 2019-11-12 | 2020-01-14 | 山东省药学科学院 | Diclofenac sodium raw material and analysis method of related substances in preparation thereof |
| CN114736131A (en) * | 2022-04-28 | 2022-07-12 | 郑州灏瑞医药科技有限公司 | Synthetic method of bromfenac sodium |
| CN116629717A (en) * | 2023-07-25 | 2023-08-22 | 山东辰欣佛都药业股份有限公司 | Eye drop production quality monitoring and management system based on big data |
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| CN116629717A (en) * | 2023-07-25 | 2023-08-22 | 山东辰欣佛都药业股份有限公司 | Eye drop production quality monitoring and management system based on big data |
| CN116629717B (en) * | 2023-07-25 | 2023-10-17 | 山东辰欣佛都药业股份有限公司 | Eye drop production quality monitoring and management system based on big data |
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Address after: Tongji Science and Technology Industrial Park, high tech Zone, Jining City, Shandong Province Patentee after: Shandong Chenxin Fodu Pharmaceutical Co.,Ltd. Address before: Tongji Science and Technology Industrial Park, high tech Zone, Jining City, Shandong Province Patentee before: Chenxin Fudu Pharmaceutical (Wenshang) Co.,Ltd. |