CN106404952B - A kind of measuring method of the sodium bromophenolate eye drops in relation to substance - Google Patents
A kind of measuring method of the sodium bromophenolate eye drops in relation to substance Download PDFInfo
- Publication number
- CN106404952B CN106404952B CN201610790645.9A CN201610790645A CN106404952B CN 106404952 B CN106404952 B CN 106404952B CN 201610790645 A CN201610790645 A CN 201610790645A CN 106404952 B CN106404952 B CN 106404952B
- Authority
- CN
- China
- Prior art keywords
- solution
- mobile phase
- sodium
- measuring method
- diluted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
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
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention belongs to drug measurement techniques fields, it particularly relates to arrive a kind of measuring method of sodium bromophenolate eye drops in relation to substance.The measuring method specific steps are as follows: lycopodine M bonded silica gel column is aoxidized using octadecylsilane chemically bonded silica column or N-, using mixture of acetonitrile-phosphate buffer as mobile phase, carry out gradient elution, Detection wavelength is 250-280nm, column temperature is 10-30 DEG C, flow velocity is 0.8-3ml/min, sample volume 20-70uL.Compared with prior art, sodium bromophenolate eye drops of the present invention realize the separation and analysis of the associated substance of bromfenac sodium in relation to the measuring method of substance, and separating degree is good, specificity is strong, high sensitivity, can be quantified using the Self-control method that correction factor is not added to these three known impurities.The measuring method has important practical significance for the quality control of sodium bromophenolate eye drops.
Description
Technical field
The invention belongs to drug measurement techniques fields, it particularly relates to arrive a kind of related substance of sodium bromophenolate eye drops
Measuring method.
Background technique
Bromfenac sodium is 2- amino -3- benzoylphenylacetic acids analog derivative, structure and Ketoprofen and Diclofenac class
Seemingly, the synthesis for the prostanoid inflammatory mediator that cyclooxygenase can be inhibited to mediate, is one of most effective cyclooxygenase-2 inhibitors,
With strength anti-inflammatory analgesic action, action intensity is 10 times of other non-steroidal anti-inflammatory drugs (NSAIDs).Pharmacological evaluation shows,
Bromfenac sodium has anti-inflammatory effect to the acute conjunctiva edema of Rat Experimental caused by arachidonic acid, carrageenan；Almost
Aqueous humor protein concentration caused by laser irradiation increases after inhibition rabbit puncture of anterior chamber.Japan is in approval Senju company in 2000
Sodium bromophenolate eye drops listing, trade name XibromTM, specification 5ml:5mg are clinically used for the inflammation of outer eye and preceding eye
The symptomatic treatment of disease property disease: blepharitis, conjunctivitis, strong film scorching (including upper strong film is scorching), post-operation inflammatory etc..
Sodium bromophenolate eye drops can generate degradation impurity during placement, and influence the quality of product.These are miscellaneous
Related substance in matter, that is, Control of drug quality, for sodium bromophenolate eye drops control impurity it is main there are 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 related substance generated with degradation, need to carry out matter in the formulation
Amount control, therefore, realize the separation and analysis of the associated substance of bromfenac sodium, the quality control for sodium bromophenolate eye drops
System has important practical significance.
Summary of the invention
In order to solve the above technical problems, that the present invention provides a kind of separating degrees is good, specificity is strong, high sensitivity Bromfenac
Measuring method of the sodium eye drops in relation to substance.
Measuring method of a kind of sodium bromophenolate eye drops in relation to substance of the present invention, the measuring method specific steps
Are as follows: lycopodine M bonded silica gel column is aoxidized using octadecylsilane chemically bonded silica column or N-, is with mixture of acetonitrile-phosphate buffer
Mobile phase carries out gradient elution, Detection wavelength 250-280nm, and column temperature is 10-30 DEG C, flow velocity 0.8-3ml/min, sample introduction
Amount is 20-70uL.
Measuring method of a kind of sodium bromophenolate eye drops in relation to substance of the present invention, the column temperature are room temperature；It is described
Detection wavelength is 266nm；
Measuring method of a kind of sodium bromophenolate eye drops in relation to substance of the present invention, the flow velocity are to adjust Bromfenac
The appearance time of sodium is 18min；The sample volume is 60uL.
Measuring method of a kind of sodium bromophenolate eye drops in relation to substance of the present invention, the 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 the mobile phase A is phosphate buffer: acetonitrile=75:25；Mobile phase B is phosphate buffer-second
Nitrile=30:70；The phosphate buffer is to take diammonium hydrogen phosphate 2.64g, is dissolved in water and is diluted to 1000ml, with phosphoric acid tune
PH value is saved to 7.3 gained.
Measuring method of a kind of sodium bromophenolate eye drops in relation to substance of the present invention, the N- aoxidize lycopodine M key
Close the preparation step of silicagel column are as follows: 1) silica gel for taking 20g to activate is in 500mL there-necked flask, then measures 100mL toluene and 40mL
Gamma-aminopropyl-triethoxy-silane, oil bath at 120 DEG C, is stirred at reflux 13h, after cooling, product successively uses toluene, and ethyl alcohol is washed
Suction filtration to no jelly is washed to exist；Drying is for 24 hours, cooling in drying box at 60 DEG C；2) step is added in the single port bottle of 500mL
1) then product sequentially adds the formalin of 120mL 35% and the acetic acid solution of 2mL, reaction 2h is stirred at room temperature, through nothing
After water-ethanol filters, it is placed in spare in 500mL there-necked flask；It takes N- oxidation lycopodine M 4g to be dissolved in appropriate aqueous solution, adjusts molten
The pH value of liquid is added in above-mentioned there-necked flask, 60 DEG C of stirrings are lower to react 10h to 8.0；It is cooling to product, successively with a large amount of secondary waters,
Dehydrated alcohol washing filters limpid to filtrate；60 DEG C of freeze-day with constant temperature 6h are filled in brown bottle after cooling in drying box and are obtained N- oxidation
Lycopodine M bonded silica gel；3) by N- oxidation lycopodine M bonded silica gel routinely dress column to get.
Measuring method of a kind of sodium bromophenolate eye drops in relation to substance of the present invention, the measuring method specific steps
Are as follows:
1) accurate to measure sodium bromophenolate eye drops 5ml, it sets in 50ml measuring bottle, mobile phase A is added to be diluted to scale, shake up, make
For test solution；Precision measures test solution 1ml, sets in 200ml measuring bottle, mobile phase A is added to be diluted to scale, shake up, and makees
For contrast solution；
2) precision weighs bromfenac sodium hydrate reference substance 25mg, sets in 25ml measuring bottle, adds flowing phased soln and is diluted to
Scale is made in every 1ml containing about the solution of anhydrous bromfenac sodium 0.93mg, shakes up, as reference substance solution stock solution；It is another accurate
Reference substance solution stock solution 1ml is measured, sets in 200ml measuring bottle, mobile phase A is added to be diluted to scale, shake up, it is molten as reference substance
Liquid；
3) precision weighs PVP K30 reference substance 200mg, sets in 10ml measuring bottle, is dissolved in water and is diluted to scale, is made
It containing the solution of 20mg in every 1ml, shakes up, precision measures 5ml, sets in 50ml measuring bottle, mobile phase A is added to be diluted to scale, shake up, and makees
For blank solution；
4) accurate to measure reference substance solution, contrast solution, blank solution and each 60 μ l of test solution, it 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
The sum of mass peak area is compared with contrast solution main peak area；
5) calculation formula
In formula: SKFor the peak area of PVP K30 in blank solution；
SXFor the peak area at peak corresponding with blank solution PVP K30 peak retention time in test solution；
SIt is rightFor the peak area of reference substance solution；
CSampleFor the mark concentration of test solution；CIt is rightFor the concentration of reference substance solution；
WIt is rightFor the weight of reference substance, mg；
1.076 be the hydrate of bromfenac sodium and the conversion factor of anhydrous bromfenac sodium.
In formula: SIt is miscellaneous、SIt is rightThe main peak area of respectively other single impurity peak areas 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 realize Bromfenac in relation to the measuring method of substance
The separation and analysis of the associated substance of sodium, and separating degree is good, specificity is strong, high sensitivity, can using not correction up because
The Self-control method of son quantifies these three known impurities.The measuring method controls the quality of sodium bromophenolate eye drops
It has important practical significance.
Specific embodiment
Below with reference to specific embodiment to sodium bromophenolate eye drops of the present invention in relation to the measuring method of substance do into
One step explanation, but the scope of protection of the present invention is not limited thereto.
Embodiment 1
Using the related substance of liquid chromatography analysis sodium bromophenolate eye drops, lycopodine M bonded silica gel is aoxidized using N-
Column carries out gradient elution, Detection wavelength 266nm using mixture of acetonitrile-phosphate buffer as mobile phase, and flow velocity is to adjust Bromfenac
The appearance time of sodium is 18min or so, and column temperature is room temperature, sample volume 60uL；Gradient program specifically:
| 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 |
Mobile phase A described in wherein: 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 step of the N- oxidation lycopodine M bonded silica gel column are as follows: the 1) silica gel for taking 20g to activate is in tri- mouthfuls of 500mL
In bottle, then 100mL toluene and the gamma-aminopropyl-triethoxy-silane of 40mL being measured, oil bath at 120 DEG C is stirred at reflux 13h, to
After cooling, product successively uses toluene, and ethanol washing, which is filtered to no jelly, to be existed；Drying is for 24 hours, cold in drying box at 60 DEG C
But；2) product of step 1) is added in the single port bottle of 500mL, then sequentially adds the formalin and 2mL of 120mL 35%
Acetic acid solution, be stirred at room temperature reaction 2h be placed in spare in 500mL there-necked flask after dehydrated alcohol filters；N- is taken to aoxidize lycopod
Alkali M 4g is dissolved in appropriate aqueous solution, is adjusted the pH value of solution to 8.0, is added in above-mentioned there-necked flask, the lower reaction of 60 DEG C of stirrings
10h；It is cooling to product, it is limpid to filtrate that suction filtration successively is washed with a large amount of secondary waters, dehydrated alcohol；60 DEG C of freeze-day with constant temperature 6h, in
N-, which is obtained, in dress brown bottle after cooling in drying box aoxidizes lycopodine M bonded silica gel；3) N- oxidation lycopodine M bonded silica gel is conventional
Fill column to get.
Confirmatory test:
1. the selection of wavelength
Precision weighs each about 10mg of impurity 1, impurity 2 and impurity 3, is set in 100ml measuring bottle respectively, is dissolved with acetonitrile and dilute
It releases to scale, shakes up, precision measures 1ml, sets in 100ml measuring bottle, mobile phase A is added to be diluted to scale, shake up, in 200~400nm
UV scanning is carried out, impurity 1, impurity 2 and impurity 3 have larger absorption at 266nm wavelength.
2. separating specificity test
Test solution: precision weighs bromfenac sodium raw material about 10mg, sets in 100ml measuring bottle, add mobile phase A dissolve and it is dilute
It releases to scale, shakes up, the solution in every 1ml containing about 0.1mg is made, as test solution.
Contrast solution: precision measures test solution 1ml, sets in 200ml measuring bottle, mobile phase A is added to be diluted to scale, shake
It is even, as contrast solution.
V solution of intermediate: precision weighs the about 10mg of intermediate V, sets in 100ml measuring bottle, and acetonitrile is added to dissolve and be diluted to
Scale shakes up, and the solution in every 1ml containing about 0.1mg is made, as V solution of intermediate.
1 solution of impurity: precision weighs the about 10mg of impurity 1, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
It is even, the solution in every 1ml containing about 0.1mg is made, as 1 solution of impurity.
2 solution of impurity: precision weighs the about 10mg of impurity 2, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
It is even, the solution in every 1ml containing about 0.1mg is made, as 2 solution of impurity.
3 solution of impurity: precision weighs the about 10mg of impurity 2, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
It is even, the solution in every 1ml containing about 0.1mg is made, as 3 solution of impurity.
Blank auxiliary solution: by the auxiliary material of recipe quantity, blank auxiliary solution is prepared.
Mixed solution: precision weighs bromfenac sodium raw material about 20mg, sets in 200ml measuring bottle, and it is each that above-mentioned dirt solution is added
1ml adds mobile phase A to dissolve and is diluted to scale, shakes up, and is made in every 1ml containing about bromfenac sodium 0.1mg, impurity each 0.5 μ g
Solution, as mixed solution.
60 μ l of contrast solution is taken to inject liquid chromatograph, adjustment flow velocity makes the retention time of bromfenac sodium hydrate be about 18
Minute, detection sensitivity is adjusted, the 20%~30% of the peak height full scale of principal component chromatographic peak is made；Take blank auxiliary molten again
Liquid, 1 solution of impurity, 2 solution of impurity, 3 solution of impurity, V solution of intermediate, mixed solution and each 60 μ l difference of test solution
Liquid chromatograph is injected, chromatogram is recorded.Peak sequence is impurity 1, bromfenac sodium, impurity 2, impurity 3, intermediate V.Test
The result shows that with being compared using octadecylsilane chemically bonded silica column in the past, after aoxidizing lycopodine M bonded silica gel column using N-,
Separate more preferable between each impurity peaks, solvent peak and auxiliary material peak do not influence the detection of main peak and impurity peaks, while to the ladder of mobile phase
Spending elution requirement, selectively requirement relatively can be lower.
3. detection limit
(1) bromfenac sodium precision weighs bromfenac sodium about 10mg, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to quarter
Degree, shakes up, and precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets
In 200ml measuring bottle, mobile phase A is added to be diluted to scale, precision draws 60 μ l and injects liquid chromatograph, it is seen that at this time
Signal-to-noise ratio (S/N) is about 3, i.e., under the chromatographic condition, the detection of bromfenac sodium is limited to 0.15ng, relative in test solution
Quantifying for bromfenac sodium is limited to 0.0025%.
(2) 1 precision of impurity weighs the about 10mg of impurity 1, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
Even, precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets 25ml amount
In bottle, add mobile phase A to be diluted to scale, shake up, then accurate absorption 2ml, sets in 10ml measuring bottle, mobile phase A is added to be diluted to scale,
It shaking up, precision draws 60 μ l and injects liquid chromatograph, chromatogram is recorded, it is seen that signal-to-noise ratio (S/N) is about 3 at this time,
I.e. under the chromatographic condition, the minimum detectable activity of impurity 1 is 0.24ng, the minimum inspection relative to bromfenac sodium in test solution
Rising limit is 0.004%.
(3) 2 precision of impurity weighs the about 10mg of impurity 2, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
Even, precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets 100ml amount
In bottle, add mobile phase A to be diluted to scale, shake up, precision draws 60 μ l and injects liquid chromatograph, records chromatogram, can from figure
Find out, signal-to-noise ratio (S/N) is about 3 at this time, i.e., under the chromatographic condition, the minimum detectable activity of impurity 2 is 0.24ng, relative to confession
The minimum detection of bromfenac sodium is limited to 0.004% in test sample solution.
(4) 3 precision of impurity weighs the about 10mg of impurity III, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
Even, precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets 100ml amount
In bottle, add mobile phase A to be diluted to scale, shake up, precision draws 60 μ l and injects liquid chromatograph, records chromatogram, can from figure
Find out, signal-to-noise ratio (S/N) is about 3 at this time, i.e., under the chromatographic condition, the minimum detectable activity of impurity 3 is 0.24ng, relative to confession
The minimum detection of bromfenac sodium is limited to 0.004% in test sample solution.
4. quantitative limit
(1) bromfenac sodium precision weighs bromfenac sodium about 10mg, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to quarter
Degree, shakes up, and precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets
In 50ml measuring bottle, mobile phase A is added to be diluted to scale, precision draws 60 μ l and injects liquid chromatograph, it is seen that believing at this time
Making an uproar than (S/N) is about 10, i.e., under the chromatographic condition, quantifying for bromfenac sodium is limited to 0.6ng, relative to bromine in test solution
Quantifying for fragrant acid sodium is limited to 0.01%, and the standard deviation RSD that measurement is liquid continuous sample introduction 6 times is less than 2.0%.
(2) 1 precision of impurity weighs the about 10mg of impurity 1, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
Even, precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets 50ml amount
In bottle, mobile phase A is added to be diluted to scale, precision draws 60 μ l and injects liquid chromatograph, records chromatogram, at this time signal-to-noise ratio (S/
It N) is about 10, i.e., under the chromatographic condition, quantifying for impurity 1 is limited to 0.6ng, determines relative to bromfenac sodium in test solution
Amount is limited to 0.01%, and the standard deviation RSD that measurement is liquid continuous sample introduction 6 times is less than 2.0%.
(3) 2 precision of impurity weighs the about 10mg of impurity 2, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
Even, precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets 50ml amount
In bottle, mobile phase A is added to be diluted to scale, precision draws 60 μ l and injects liquid chromatograph, records chromatogram, at this time signal-to-noise ratio (S/
It N) is about 10, i.e., under the chromatographic condition, quantifying for impurity 2 is limited to 0.6ng, determines relative to bromfenac sodium in test solution
Amount is limited to 0.01%, and the standard deviation RSD that measurement is liquid continuous sample introduction 6 times is less than 2.0%.
(4) 3 precision of impurity weighs the about 10mg of impurity 3, sets in 100ml measuring bottle, adds acetonitrile to dissolve and is diluted to scale, shakes
Even, precision draws 1ml, sets in 200ml measuring bottle, is diluted to scale with mobile phase A, shakes up, then accurate absorption 1ml, sets 50ml amount
In bottle, mobile phase A is added to be diluted to scale, precision draws 60 μ l and injects liquid chromatograph, records chromatogram, at this time signal-to-noise ratio (S/
It N) is about 10, i.e., under the chromatographic condition, quantifying for impurity 3 is limited to 0.6ng, determines relative to bromfenac sodium in test solution
Amount is limited to 0.01%, and the standard deviation RSD that measurement is liquid continuous sample introduction 6 times is less than 2.0%.
5. the measurement of impurity correction factor
Precision weighs each about 10mg of bromfenac sodium reference substance, impurity 1, impurity 2 and impurity 3, is set in 100ml measuring bottle respectively,
Scale is dissolved and be diluted to acetonitrile, is shaken up, and each accurate measurement 1ml sets in 200ml measuring bottle respectively, dissolved with mobile phase A and dilute
It releases to scale, shakes up.
Precision takes each 60 μ l sample introduction of above-mentioned solution respectively, records chromatogram, and same method measures six times respectively, and concrete outcome is shown in
Following table.
From the above data, impurity 1, impurity 2 and 3 relative response factor of impurity are within the scope of 0.9-1.1, so can
To be quantified using the Self-control method that correction factor is not added to these three known impurities.
Claims (5)
1. a kind of measuring method of sodium bromophenolate eye drops in relation to substance, which is characterized in that the measuring method specific steps are as follows:
Lycopodine M bonded silica gel column is aoxidized using N-, using mixture of acetonitrile-phosphate buffer as mobile phase, carries out gradient elution, Detection wavelength
For 250-280nm, column temperature is 10-30 DEG C, flow velocity 0.8-3mL/min, and sample volume is 20-70 μ L；
The gradient:
Wherein the mobile phase A is phosphate buffer: acetonitrile=75:25；Mobile phase B be mixture of acetonitrile-phosphate buffer=
30:70；The phosphate buffer is to take diammonium hydrogen phosphate 2.64g, is dissolved in water and is diluted to 1000mL, with phosphorus acid for adjusting pH
It is worth to 7.3 gained.
2. measuring method of a kind of sodium bromophenolate eye drops in relation to substance according to claim 1, which is characterized in that described
Column temperature is room temperature；The Detection wavelength is 266nm.
3. measuring method of a kind of sodium bromophenolate eye drops in relation to substance according to claim 1, which is characterized in that described
Flow velocity is that the appearance time of adjusting bromfenac sodium is 18min；The sample volume is 60 μ L.
4. measuring method of a kind of sodium bromophenolate eye drops in relation to substance according to claim 1, which is characterized in that described
The preparation step of N- oxidation lycopodine M bonded silica gel column are as follows: the 1) silica gel for taking 20g to activate is in 500mL there-necked flask, then measures
The gamma-aminopropyl-triethoxy-silane of 100mL toluene and 40mL, oil bath at 120 DEG C, is stirred at reflux 13h, after cooling, product
Toluene is successively used, ethanol washing, which is filtered to no jelly, to be existed；Drying is for 24 hours, cooling in drying box at 60 DEG C；2) in 500mL
Single port bottle in be added step 1) product, then sequentially add the formalin of 120mL 35% and the acetic acid solution of 2mL, room
Temperature is stirred to react 2h, after dehydrated alcohol filters, is placed in spare in 500mL there-necked flask；N- oxidation lycopodine M 4g is taken to be dissolved in suitable
It measures in aqueous solution, adjusts the pH value of solution to 8.0, be added in above-mentioned there-necked flask, 60 DEG C of stirrings are lower to react 10h；It is cooling to product,
It is limpid to filtrate that suction filtration successively is washed with a large amount of secondary waters, dehydrated alcohol；60 DEG C of freeze-day with constant temperature 6h are filled after cooling in drying box
In brown bottle, N- oxidation lycopodine M bonded silica gel is obtained；3) by N- oxidation lycopodine M bonded silica gel routinely dress column to get.
5. measuring method of a kind of sodium bromophenolate eye drops in relation to substance according to claim 1, which is characterized in that described
Measuring method specific steps are as follows:
1) accurate to measure sodium bromophenolate eye drops 5mL, it sets in 50mL measuring bottle, mobile phase A is added to be diluted to scale, shake up, as confession
Test sample solution；Precision measures test solution 1mL, sets in 200mL measuring bottle, mobile phase A is added to be diluted to scale, shake up, as right
According to solution；
2) precision weighs bromfenac sodium hydrate reference substance 25mg, sets in 25mL measuring bottle, adds flowing phased soln and is diluted to scale,
It is made in every 1mL containing about the solution of anhydrous bromfenac sodium 0.93mg, shakes up, as reference substance solution stock solution；Another accurate measurement
Reference substance solution stock solution 1mL, sets in 200mL measuring bottle, mobile phase A is added to be diluted to scale, shake up, as reference substance solution；
3) precision weighs PVP K30 reference substance 200mg, sets in 10mL measuring bottle, is dissolved in water and is diluted to scale, is made every
Containing the solution of 20mg in 1mL, shaking up, precision measures 5mL, and it sets in 50mL measuring bottle, mobile phase A is added to be diluted to scale, shake up, as
Blank solution；
4) accurate to measure reference substance solution, contrast solution, blank solution and each 60 μ L of test solution, it 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
The sum of area is compared with contrast solution main peak area.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610790645.9A CN106404952B (en) | 2016-08-31 | 2016-08-31 | A kind of measuring method of the sodium bromophenolate eye drops in relation to substance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610790645.9A CN106404952B (en) | 2016-08-31 | 2016-08-31 | A kind of measuring method of the sodium bromophenolate eye drops in relation to substance |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106404952A CN106404952A (en) | 2017-02-15 |
| CN106404952B true CN106404952B (en) | 2019-06-11 |
Family
ID=58000675
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610790645.9A Active CN106404952B (en) | 2016-08-31 | 2016-08-31 | A kind of measuring method of the sodium bromophenolate eye drops in relation to substance |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106404952B (en) |
Families Citing this family (4)
| 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 |
| CN113866282A (en) * | 2020-06-30 | 2021-12-31 | 天津药业研究院股份有限公司 | Separation and detection method for isomer impurities in 3-halogenated-7- (4-bromobenzoyl) -1-hydro-indole and application 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 |
| 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 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683242A (en) * | 1985-10-28 | 1987-07-28 | A. H. Robins Company, Incorporated | Transdermal treatment for pain and inflammation with 2-amino-3-aroylbenzeneacetic acids, salts and esters |
| US4910225A (en) * | 1988-01-27 | 1990-03-20 | Senju Pharmaceutical Co., Ltd. | Locally administrable therapeutic composition for inflammatory disease |
| CN1700913A (en) * | 2003-01-21 | 2005-11-23 | 千寿制药株式会社 | Aqueous liquid preparation containing 2-amino-3-(4-bromobenzoyl)phenylacetic acid |
| CN104177272A (en) * | 2014-06-16 | 2014-12-03 | 广东众生药业股份有限公司 | Preparation method of bromfenac sodium |
-
2016
- 2016-08-31 CN CN201610790645.9A patent/CN106404952B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683242A (en) * | 1985-10-28 | 1987-07-28 | A. H. Robins Company, Incorporated | Transdermal treatment for pain and inflammation with 2-amino-3-aroylbenzeneacetic acids, salts and esters |
| US4910225A (en) * | 1988-01-27 | 1990-03-20 | Senju Pharmaceutical Co., Ltd. | Locally administrable therapeutic composition for inflammatory disease |
| CN1700913A (en) * | 2003-01-21 | 2005-11-23 | 千寿制药株式会社 | Aqueous liquid preparation containing 2-amino-3-(4-bromobenzoyl)phenylacetic acid |
| CN104177272A (en) * | 2014-06-16 | 2014-12-03 | 广东众生药业股份有限公司 | Preparation method of bromfenac sodium |
Non-Patent Citations (2)
| Title |
|---|
| RP-HPLC法测定溴芬酸钠含量和有关物质;阚家义 等;《药物分析杂志》;20090430;第29卷(第4期);666-668 |
| RP-HPLC测定溴芬酸钠滴眼液中苯扎溴铵的含量;杨海霞 等;《食品与药品》;20151231;第17卷(第2期);111-113 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106404952A (en) | 2017-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106404952B (en) | A kind of measuring method of the sodium bromophenolate eye drops in relation to substance | |
| Perez et al. | Switching reversibility to irreversibility in glycogen synthase kinase 3 inhibitors: clues for specific design of new compounds | |
| Zhang et al. | Time-resolved fluoroimmunoassay as an advantageous analytical method for assessing the total concentration and environmental risk of fluoroquinolones in surface waters | |
| CN107037153A (en) | The method that high performance liquid chromatography detects genotoxicity impurity in AL58805 bulk drugs or pharmaceutical preparation | |
| CN102702008B (en) | Agomelatine sulfuric acid composition and preparation method thereof | |
| CN110746321B (en) | Malononitrile Schiff base hypochlorous acid fluorescent probe and preparation method thereof | |
| CN102276624A (en) | Olanzapine related substance and preparation method as well as high-efficiency liquid-phase chromatographic analysis method thereof | |
| CN114280176B (en) | Method for detecting related substances in oxaragroli by HPLC | |
| CN107870209B (en) | Method for determining impurity content in linagliptin bulk drug | |
| CN104804079A (en) | Imatinib immunogen, derivative, synthesis method, specific antibody and detection reagent and preparation methods | |
| CN109900830A (en) | Using the method and application of sulfonamides impurity in HPLC separation determination celecoxib | |
| CN109928958A (en) | A kind of voriconazole derivate, its synthetic method and a kind of voriconazole immunogene, preparation method and its application | |
| US11655239B2 (en) | Fused ring pyrimidine amino compound and preparation method, pharmaceutical composition, and use thereof | |
| CN109765316B (en) | Method for detecting levetiracetam from medicine | |
| CN114544851B (en) | Analysis method for determining o-chlorophenylglycine methyl tartrate and impurities | |
| CN108072710A (en) | A kind of Edaravone Sodium Chloride Injections Related Substances detection method | |
| CN114689737B (en) | Analysis method of S-o-chlorophenylglycine methyl tartrate related substances | |
| CN104297354B (en) | The detection method of impurity in a kind of high effective liquid chromatography for measuring amyl ethyl quin ether hydrochloride | |
| Singh et al. | High performance liquid chromatography method for the pharmacokinetic study of bicalutamide SMEDDS and suspension formulations after oral administration to rats | |
| CN107356682B (en) | HPLC method for detecting 4-benzyloxy benzylidene aniline in 4-benzyloxy benzylidene-4-fluoroaniline | |
| US20090118342A1 (en) | Design and synthesis of biotinylated probes for n-acyl-ethanolamines | |
| CN108047117A (en) | It is used to prepare silodosin benzazolyl compounds and preparation method thereof | |
| CN109001342B (en) | High performance liquid chromatography method for detecting N-2, 3-dimethoxybenzyl piperonylethylamine and salt content thereof | |
| CN111351867B (en) | Analysis method for determining substances related to lubiprostone test sample | |
| CN104569260A (en) | Method for detecting residual amount of formaldehyde in colistimethate sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder |
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. |
|
| CP01 | Change in the name or title of a patent holder |