CN108760951A - A method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film - Google Patents
A method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film Download PDFInfo
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Abstract
The invention discloses a kind of methods of a variety of residual organic solvents in detection Bioabsorbable Polyesters film, using headspace gas chromatography, detect five kinds of ethyl alcohol in Bioabsorbable Polyesters film, acetone, dichloromethane, ethyl acetate and dioxane organic solvents simultaneously, the detection method high sensitivity of the present invention, reproducible, accuracy is high；Due to using external standard method, not needing other standard substances as internal standard compound, it is only necessary to which the pure material of detected components, the requirement to sample introduction precision is low, easy to operate；Due to using headspace gas chromatography, interference of the poly-lactic acid products to detection is avoided, gas phase instrument system will not be polluted, and the short chain hydrocarbon micromolecular compound generated after decomposing will not bring testing result interference；The detection method of the present invention can avoid the interference of the small molecular weight impurities P-Dioxanes such as lactic acid and cyclic monomer in polylactic acid-based high molecular material, can accurately detect the residual quantity of dioxane.
Description
Technical field
The present invention relates to technical field of analysis and detection, a variety of residuals in specifically a kind of detection Bioabsorbable Polyesters film
The method of organic solvent.
Background technology
Polylactic acid-based guiding film is a kind of Bioabsorbable Polyesters film, it is to be with polylactic acid-based biological absorbable macromolecule
Raw material is prepared by special process, is used for guide tissue regeneration (GTR) or Guided Bone Regeneration (GBR), and guide work
It is taken out with operation is not had to after the completion, it can be completely by bio-absorbable, it is therefore desirable to higher safety.In addition, in raw material and product
Production process in inevitably use organic solvent, since polylactic acid-based biological absorbable high molecular material is that one kind does not have
There is a fixed member amount, but the mixed system of different molecular weight homologue, it is given birth in polylactic acid-based biological absorbable high molecular material
During production, in order to improve the homogeneity of high molecular material molecular weight, solvent appropriate is usually selected to be purified, and guide
Also it can make solvent or pore-foaming agent using organic volatile appropriate during film preparation, since these volatile matters are in post-processing
It is likely to be completely removed, therefore to the safe to use there are potential danger of product, thus, establish accurately analysis detection
The method of a variety of residual solvents is very necessary in polylactic acid-based absorbable guiding film.
Current detection method has the disadvantage that：First, can only detect polylactic acid material one of which or two kinds
Solvent, and since the boiling point of the small molecular weight impurities such as lactic acid and cyclic monomer and the boiling point of dioxane are close, polylactic acid
The detection of small molecule meeting P-Dioxane in product has interference, and dioxane can not accurately be detected using existing method
Content；Second, the particularity of poly-lactic acid material can have interference to the detection of dissolvent residual, this is because, polylactic acid-based material
The decomposition temperature of material is higher, and the polylactic acid-based macromolecule that direct injected is seen in can pollute gas phase instrument system, such as injection port, lining
Pipe, chromatographic column etc., and short chain hydrocarbon micromolecular compound is will produce after decomposing, interference can be brought to detection；Third, in
Residual solvent levels specified in 2015 editions four general rules, 0861 residual solvent measuring methods of magnificent people's republic's pharmacopeia require and gather
Lactic acid class can absorb the raw material and preparation process of guiding film, it is necessary to control ethyl alcohol (third class solvent), acetone (third class solvent),
Dichloromethane (the second class solvent), ethyl acetate (third class solvent), the residual quantity of dioxane (the second class solvent) ensure poly-
Lactic acid class can absorb the safe to use of guiding film.2015 editions four 0861 residual solvents of general rule of Pharmacopoeia of People's Republic of China measure
Regulation ethyl alcohol in method, acetone, ethyl acetate limit be 0.5%, the limit of dichloromethane is 0.06%, the limit of dioxane
Degree is 0.038%.
Invention content
To solve the above problems, remaining the object of the present invention is to provide a variety of in a kind of detection Bioabsorbable Polyesters film
The method of solvent.
The present invention to achieve the above object, is achieved through the following technical solutions：
A method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film, using headspace gas chromatography,
Five kinds of ethyl alcohol in Bioabsorbable Polyesters film, acetone, dichloromethane, ethyl acetate and dioxane organic solvents are detected simultaneously,
The Bioabsorbable Polyesters film is polylactic acid-based guiding film；Specifically include following steps：
1. selected chromatographic condition：
Agilent 6890N gas chromatographs (fid detector), Agilent 7697A head-space samplers；
Chromatographic column：DB-624, specification are 30m × 0.530mm × 3.0 μm；
Column temperature：Temperature programming, 95~105 DEG C of initial temperature keep 4~7min, then with the heating rate of 30 DEG C/min
4~7min is kept after being warming up to 175~185 DEG C；
Injector temperature：195~210 DEG C；
Detector temperature：240~260 DEG C；
Carrier gas：Nitrogen, flow velocity are 2.0~4.0mL/min；
Split ratio：5~15:1；
Head space equilibrium temperature：95~110 DEG C, 20~40min of equilibration time；
Input mode：Headspace sampling mode, sample size 1mL；
2. the preparation of solution
The preparation of reference substance stock solution：Precision weighs 0.98~1.02g of ethyl alcohol, 0.98~1.02g of acetone, ethyl acetate
0.98~1.02g adds dmso solution and constant volume is in 100mL measuring bottles, respectively as ethyl alcohol, acetoneand ethyl acetate pair
According to product stock solution；1.18~1.22g of dichloromethane, 0.74~0.78g of dioxane are taken, accurately weighed, respectively plus dimethyl is sub-
Sulfone dissolving and constant volume is in 100mL measuring bottles, takes 10mL in 100mL measuring bottles, respectively plus dmso solution and constant volume in
Dichloromethane and dioxane reference substance stock solution are used as in 100mL measuring bottles；
Mix the preparation of reference substance stock solution：
Precision weighs 0.98~1.02g of ethyl alcohol, 0.98~1.02g of acetone, 0.98~1.02g of ethyl acetate and is placed in 100ml
The first volumetric flask in, spare, then precision weighs 1.18~1.22g of dichloromethane again and 0.74~0.78g of dioxane is set
In the second volumetric flask of 100ml, dmso solution and constant volume is added, solution 10ml is taken to be placed in the first volumetric flask,
Dmso solution ethyl alcohol, acetoneand ethyl acetate are added into the first volumetric flask, and mixing reference substance reserve is obtained after constant volume
Liquid；
3. system suitability
Take the reference substance stock solution and mixing reference substance reserve of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane
Each 10ml of liquid is respectively placed in 100ml volumetric flasks, with dimethyl sulfoxide (DMSO) dilution and constant volume, respectively 5ml is taken to be placed in ml headspace bottle, close
It seals, sample introduction is balanced under the conditions of head space, record collection of illustrative plates；
4. precision test
Precision measures the reference substance stock solution 5ml of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane, is placed in
It with dmso solution and constant volume in 50ml volumetric flasks, takes 5mL in ml headspace bottle, seals, sample introduction is balanced under the conditions of head space, even
Continuous sample introduction 6 times, records the relative standard deviation RSD of each reference substance；
5. linear test
By the volume gradient accurate reference substance storage for measuring ethyl alcohol, acetone, ethyl acetate, dichloromethane and dioxane respectively
Standby liquid, is respectively placed in same volume volumetric flask, adds dmso solution and constant volume, prepares a series of linear test solution,
Then it takes 5ml to be placed in ml headspace bottle respectively to seal, sample introduction is balanced under the conditions of head space, then with ethyl alcohol, acetone, ethyl acetate, two
The peak area of the linear test liquid of chloromethanes and dioxane is that ordinate establishes linear regression curves with a concentration of abscissa；
6. recovery test
3 parts of mixing reference substance stock solution is measured by volume gradient is accurate respectively, is respectively placed in same volume volumetric flask, with two
Methyl sulfoxide dissolving and constant volume, precision measure above-mentioned each solution 5ml, are placed in the tops 10ml equipped with 0.98~1.02g samples to be tested
In empty bottle, sealing, heating water bath to sample to be tested is completely dissolved, is cooled to room temperature, and obtains the sample-adding solution of 3 concentration, each
Concentration is parallel to prepare 3 parts, and sample introduction is balanced under the conditions of head space, calculates each component rate of recovery；
7. detection limit and quantitative limit experiment
Use the reference substance of dimethyl sulfoxide (DMSO) alcohol,diluted, acetone, dichloromethane, ethyl acetate and dioxane respectively successively
Stock solution dilutes step by step, calculates detection limit with signal-to-noise ratio S/N >=3, quantitative limit is calculated with signal-to-noise ratio S/N >=10；
8. sample detection
Precision weighs polylactic acid-based 0.98~1.02g of guiding film, is placed in ml headspace bottle, and dimethyl sulfoxide (DMSO) 5ml sealings are added
Afterwards, heating water bath (temperature is at 90 DEG C or less) to polylactic acid-based guiding film is completely dissolved, and is cooled to room temperature as product to be tested solution,
Sample introduction is balanced under the conditions of head space, records chromatogram；
Precision draws mixing reference substance stock solution 1ml, is placed in 10ml volumetric flasks, with dmso solution constant volume, makees
For mixed reference substance solution, 5ml mixed reference substance solutions is taken to be placed in ml headspace bottle, balances sample introduction under the conditions of sealing head space, record
Chromatogram, by external standard method with ethyl alcohol, acetone, dichloromethane, ethyl acetate, dioxy six in the polylactic acid-based guiding film of calculated by peak area
The content of ring.
Preferably, step 1. in select chromatographic condition be：
Column temperature：Column temperature：Temperature programming, 100 DEG C of initial temperature keep 5min, then with the heating rate liter of 30 DEG C/min
Temperature is to keeping 5min after 180 DEG C；
Injector temperature：200℃；
Detector temperature：250℃；
Carrier gas：Nitrogen, flow velocity 3.0mL/min；
Split ratio：10:1；
Head space equilibrium temperature：100 DEG C, equilibration time 30min.
Preferably, step 2. in the preparation process of reference substance stock solution be：
Ethyl alcohol 1.00g, acetone 1.00g, ethyl acetate 1.00g are taken, it is accurately weighed, respectively plus dmso solution and fixed
It is dissolved in 100mL measuring bottles, as ethyl alcohol, acetoneand ethyl acetate reference substance stock solution；Take dichloromethane 1.20g, dioxane
0.76g, it is accurately weighed, add dmso solution respectively and constant volume is in 100mL measuring bottles, takes 10mL in 100mL measuring bottles, point
Not plus dmso solution and constant volume are used as dichloromethane and dioxane reference substance stock solution in 100mL measuring bottles.
Preferably, 5. linear test is step：
The accurate reference substance stock solution for measuring ethyl alcohol, acetone, ethyl acetate, dichloromethane and dioxane respectively
0.20ml, 0.40ml, 0.60ml, 0.80ml, 1.00ml and 1.20ml are respectively placed in 10ml volumetric flasks, add dimethyl sulfoxide (DMSO)
Simultaneously constant volume is dissolved, a series of linear test solution is prepared.
Preferably, 6. recovery test is step：
It takes 0.80ml, 1.00ml and 1.20ml mixing reference substance stock solution to be respectively placed in 10ml volumetric flasks, diformazan is added
The dissolving of base sulfoxide and constant volume, take the above-mentioned solution of 5ml to be placed in the ml headspace bottle equipped with the polylactic acid-based guiding films of 1.00g respectively, seal,
80 DEG C of heating water baths to polylactic acid-based guiding film is completely dissolved, and is cooled to room temperature, and the sample-adding solution of 3 concentration, Mei Genong are obtained
Parallel 3 parts of preparation is spent, sample introduction is balanced under the conditions of head space, calculates each component rate of recovery.
Preferably, 8. sample detection is step：
Precision weighs polylactic acid-based guiding film 1.00g, is placed in ml headspace bottle, after dimethyl sulfoxide (DMSO) sealing is added, 80 DEG C of water
Bath is heated to polylactic acid-based guiding film and is completely dissolved, and is cooled to room temperature as product to be tested solution, then by product to be tested solution and second
The reference substance stock solution difference headspace sampling of alcohol, acetone, dichloromethane, ethyl acetate and dioxane, records chromatogram, by outer
Mark method is with the content of ethyl alcohol, acetone, dichloromethane, ethyl acetate, dioxane in the polylactic acid-based guiding film of calculated by peak area.
The present invention has the following advantages compared with prior art：
The method of a variety of residual organic solvents in the detection Bioabsorbable Polyesters film of the present invention, using headspace gas chromatography
Method can detect five kinds of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane solvents, high sensitivity, repeatability simultaneously
Good, accuracy is high；Due to using external standard method, not needing other standard substances as internal standard compound, it is only necessary to detected components
Pure material, the requirement to sample introduction precision is low, easy to operate；Due to using headspace gas chromatography, poly-lactic acid products are avoided
Interference to detection will not pollute gas phase instrument system, and the short chain hydrocarbon micromolecular compound generated after decomposing will not be right
Testing result brings interference；The detection method of the present invention can avoid the lactic acid in polylactic acid-based high molecular material and cyclic monomer
The interference of equal small molecular weight impurities P-Dioxane, can accurately detect the residual quantity of dioxane.
Description of the drawings
Fig. 1 Ethanol System compatibility tests gas chromatogram (1. ethyl alcohol of reference numeral；2. dimethyl sulfoxide (DMSO))；
Fig. 2 acetone system suitability tests gas chromatogram (1. acetone of reference numeral；2. dimethyl sulfoxide (DMSO))；
Fig. 3 dichloromethane system suitability tests gas chromatogram (1. dichloromethane of reference numeral；2. dimethyl sulfoxide (DMSO))；
Fig. 4 ethyl acetate system suitability tests gas chromatogram (1. ethyl acetate of reference numeral；2. dimethyl sulfoxide (DMSO))；
Fig. 5 dioxane system suitability tests gas chromatogram (1. dioxane of reference numeral；2. dimethyl sulfoxide (DMSO))；
Fig. 6 ethyl alcohol, dichloromethane, acetone, ethyl acetate and dioxane hybrid system compatibility test gas chromatogram
(1. ethyl alcohol of reference numeral；2. dichloromethane；3. acetone；4. ethyl acetate；5. dioxane；6. dimethyl sulfoxide (DMSO)).
Specific implementation mode
Below in conjunction with specific embodiment, the invention will be further described.
Embodiment 1
A method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film, using headspace gas chromatography,
Five kinds of ethyl alcohol in Bioabsorbable Polyesters film, acetone, dichloromethane, ethyl acetate and dioxane organic solvents are detected simultaneously,
The Bioabsorbable Polyesters film is polylactic acid-based guiding film；Specifically include following steps：
1. selected chromatographic condition：
Instrument：Agilent 6890N gas chromatographs (fid detector), Agilent 7697A head-space samplers；
Agilent chromatographic work stations；
Agents useful for same is chromatographically pure, polylactic acid Guided Bone Regeneration film (lot number 20170112)；
Chromatographic column：DB-624, specification are 30m × 0.530mm × 3.0 μm；
Column temperature：Temperature programming, 100 DEG C of initial temperature are kept 5min, are then warming up to the heating rate of 30 DEG C/min
5min is kept after 180 DEG C；
Injector temperature：200℃；
Detector temperature：250℃；
Carrier gas：Nitrogen, flow velocity 3.0mL/min；
Split ratio：10:1；
Head space equilibrium temperature：100 DEG C, equilibration time 30min；
Input mode：Headspace sampling mode, sample size 1mL；
2. the preparation of solution
The preparation of reference substance stock solution：Precision weighs ethyl alcohol 1.00g, acetone 1.00g, ethyl acetate 1.00g, adds two respectively
Simultaneously constant volume is in 100mL measuring bottles for methyl sulfoxide dissolving, as ethyl alcohol, acetoneand ethyl acetate reference substance stock solution；Take dichloromethane
Alkane 1.20g, dioxane 0.76g, accurately weighed, adding dmso solution respectively, simultaneously constant volume takes 10mL in 100mL measuring bottles
In 100mL measuring bottles, adds dmso solution respectively and constant volume is used as dichloromethane and dioxane pair in 100mL measuring bottles
According to product stock solution；
Mix the preparation of reference substance stock solution：
Precision weighs ethyl alcohol 1.00g, acetone 1.00g, ethyl acetate 1.00g and is placed in the first volumetric flask of 100ml, standby
With then precision weighs dichloromethane 1.20g again and dioxane 0.76g is placed in the second volumetric flask of 100ml, and diformazan is added
The dissolving of base sulfoxide and constant volume, take solution 10ml to be placed in the first volumetric flask, and it is molten that dimethyl sulfoxide (DMSO) is added into the first volumetric flask
Ethyl alcohol, acetoneand ethyl acetate are solved, mixing reference substance stock solution is obtained after constant volume；
3. system suitability
Take the reference substance stock solution and mixing reference substance reserve of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane
Each 10ml of liquid is respectively placed in 100ml volumetric flasks, with dimethyl sulfoxide (DMSO) dilution and constant volume, respectively 5ml is taken to be placed in ml headspace bottle, close
It seals, sample introduction is balanced under the conditions of head space, record collection of illustrative plates；The results are shown in Table 1 for the retention time and separating degree of each component, each component
System suitability collection of illustrative plates is as shown in figs. 1 to 6.
The retention time and separating degree result of 1 each component of table
4. precision test
Precision measures the reference substance stock solution 5ml of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane, is placed in
It with dmso solution and constant volume in 50ml volumetric flasks, takes 5mL in ml headspace bottle, seals, sample introduction is balanced under the conditions of head space, even
Continuous sample introduction 6 times, records the relative standard deviation RSD of each reference substance, as shown in table 2, from the results, it was seen that each component
RSD values are within 5%.
The RSD results table (n=6) of 2 each reference substance of table
5. linear test
The accurate reference substance stock solution for measuring ethyl alcohol, acetone, ethyl acetate, dichloromethane and dioxane respectively
0.20ml, 0.40ml, 0.60ml, 0.80ml, 1.00ml and 1.20ml are respectively placed in 10ml volumetric flasks, add dimethyl sulfoxide (DMSO)
Simultaneously constant volume is dissolved, a series of linear test solution is prepared, then takes 5ml to be placed in ml headspace bottle respectively and seal, under the conditions of head space
Sample introduction is balanced, is then with the peak area of the linear test solution of ethyl alcohol, acetone, ethyl acetate, dichloromethane and dioxane
Ordinate establishes linear regression curves with a concentration of abscissa, and the results are shown in Table 3.
3 linear test measurement result of table
6. recovery test
It takes 0.80ml, 1.00ml and 1.20ml mixing reference substance stock solution to be respectively placed in 10ml volumetric flasks, diformazan is added
The dissolving of base sulfoxide and constant volume, take the above-mentioned solution of 5ml to be placed in the ml headspace bottle equipped with the polylactic acid-based guiding films of 1g respectively, seal, water
Bath is heated to polylactic acid-based guiding film and is completely dissolved, and bath temperature obtains 3 concentration generally at 90 DEG C hereinafter, be cooled to room temperature
Sample-adding solution, each concentration is parallel to prepare 3 parts, and sample introduction is balanced under the conditions of head space, calculates each component rate of recovery, as a result such as table
Shown in 4.
4 recovery test measurement result of table
7. detection limit and quantitative limit experiment
Use the reference substance of dimethyl sulfoxide (DMSO) alcohol,diluted, acetone, dichloromethane, ethyl acetate and dioxane respectively successively
Stock solution dilutes step by step, calculates detection limit with signal-to-noise ratio S/N >=3, quantitative limit is calculated with signal-to-noise ratio S/N >=10；5mL is taken respectively
It in ml headspace bottle, seals, sample introduction is balanced under the conditions of head space, record chromatogram.Detection limit and quantitative limit measurement result are shown in Table 5.
The detection limit and quantitative limit result of 5 each component of table
8. sample detection
Precision weighs polylactic acid-based guiding film 1.00g, is placed in ml headspace bottle, after dimethyl sulfoxide (DMSO) 5ml sealings are added, water-bath
Polylactic acid-based guiding film is heated to be completely dissolved, bath temperature generally at 90 DEG C hereinafter, Optimal Temperature be 80 DEG C, be cooled to room temperature
As product to be tested solution, sample introduction is balanced under the conditions of head space, records chromatogram；
Precision draws mixing reference substance stock solution 1ml, is placed in 10ml volumetric flasks, with dmso solution constant volume, makees
For mixed reference substance solution, 5ml mixed reference substance solutions is taken to be placed in ml headspace bottle, balances sample introduction under the conditions of sealing head space, record
Chromatogram, by external standard method with ethyl alcohol, acetone, dichloromethane, ethyl acetate, dioxy six in the polylactic acid-based guiding film of calculated by peak area
The content of ring.According to《Pharmacopoeia of People's Republic of China》The bound requirements of 2015 editions common residual solvents, ethyl alcohol must not exceed
0.5%, acetone must not exceed 0.5%, and dichloromethane must not exceed 0.06%, and ethyl acetate must not exceed 0.5%, dioxane
It must not exceed 0.038%.
The residual quantity point of ethyl alcohol in sample, acetone, dichloromethane, ethyl acetate, dioxane is detected according to the method described above
It is not：0.019%, 0.0021%, 0.00057%, 0.00014% and 0.0045%, the residual quantity of five kinds of solvents is satisfied by《In
Magnificent people's republic's pharmacopeia》Margin of safety requirement.
Embodiment 2
A method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film, using headspace gas chromatography,
Five kinds of ethyl alcohol in Bioabsorbable Polyesters film, acetone, dichloromethane, ethyl acetate and dioxane organic solvents are detected simultaneously,
The Bioabsorbable Polyesters film is polylactic acid-based guiding film；Specifically include following steps：
1. selected chromatographic condition：
Instrument：Agilent 6890N gas chromatographs (fid detector), Agilent 7697A head-space samplers；
Agilent chromatographic work stations；
Reagent：Agents useful for same is chromatographically pure；Polylactic acid-based absorbable Guided Bone Regeneration film (lot number 20170517)；
Chromatographic column：DB-624, specification are 30m × 0.530mm × 3.0 μm；
Column temperature：Temperature programming, 95 DEG C of initial temperature keep 4min, are then warming up to 175 with the heating rate of 30 DEG C/min
4min is kept after DEG C；
Injector temperature：195℃；
Detector temperature：240℃；
Carrier gas：Nitrogen, flow velocity 2.0mL/min；
Split ratio：5:1；
Head space equilibrium temperature：95 DEG C, equilibration time 20min；
Input mode：Headspace sampling mode, sample size 1mL；
2. the preparation of solution
The preparation of reference substance stock solution：Precision weighs ethyl alcohol 0.98g, acetone 0.98g, ethyl acetate 0.98g, adds two respectively
Simultaneously constant volume is in 100mL measuring bottles for methyl sulfoxide dissolving, as ethyl alcohol, acetoneand ethyl acetate reference substance stock solution；Take dichloromethane
Alkane 1.18g, dioxane 0.74g, accurately weighed, adding dmso solution respectively, simultaneously constant volume takes 10mL in 100mL measuring bottles
In 100mL measuring bottles, adds dmso solution respectively and constant volume is used as dichloromethane and dioxane pair in 100mL measuring bottles
According to product stock solution；
Mix the preparation of reference substance stock solution：
Precision weighs ethyl alcohol 0.98g, acetone 0.98g, ethyl acetate 0.98g and is placed in the first volumetric flask of 100ml, standby
With then precision weighs dichloromethane 1.18 again and dioxane 0.74g is placed in the second volumetric flask of 100ml, and diformazan is added
The dissolving of base sulfoxide and constant volume, take solution 10ml to be placed in the first volumetric flask, and it is molten that dimethyl sulfoxide (DMSO) is added into the first volumetric flask
Ethyl alcohol, acetoneand ethyl acetate are solved, mixing reference substance stock solution is obtained after constant volume；
3. system suitability
Take the reference substance stock solution and mixing reference substance reserve of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane
Each 10ml of liquid is respectively placed in 100ml volumetric flasks, with dimethyl sulfoxide (DMSO) dilution and constant volume, respectively 5ml is taken to be placed in ml headspace bottle, close
It seals, sample introduction is balanced under the conditions of head space, record collection of illustrative plates；
4. precision test
Precision measures the reference substance stock solution reference substance reserve of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane
Liquid 5ml is placed in 50ml volumetric flasks with dmso solution and constant volume, takes 5mL in ml headspace bottle, seal, under the conditions of head space
Sample introduction, continuous sample introduction 6 times are balanced, headspace sampling records the relative standard deviation RSD of each reference substance；
5. linear test
By the volume gradient accurate reference substance storage for measuring ethyl alcohol, acetone, ethyl acetate, dichloromethane and dioxane respectively
Standby liquid, is respectively placed in same volume volumetric flask, adds dmso solution and constant volume, prepares a series of linear test solution,
Then it takes 5ml to be placed in ml headspace bottle respectively to seal, sample introduction is balanced under the conditions of head space, then with ethyl alcohol, acetone, ethyl acetate, two
The peak area of the linear test solution of chloromethanes and dioxane is ordinate, with a concentration of abscissa, establishes linear regression song
Line；
6. recovery test
3 parts of mixing reference substance stock solution is measured by volume gradient is accurate respectively, is respectively placed in same volume volumetric flask, with two
Methyl sulfoxide dissolving and constant volume, precision measure above-mentioned each solution 5ml, are placed in the 10ml ml headspace bottles equipped with 0.98g samples to be tested,
Sealing, 80 DEG C of heating water bath to samples to be tested are completely dissolved, are cooled to room temperature, and obtain the sample-adding solution of 3 concentration, each concentration
It is parallel to prepare 3 parts, sample introduction is balanced under the conditions of head space, calculates each component rate of recovery；
7. detection limit and quantitative limit experiment
Use the reference substance of dimethyl sulfoxide (DMSO) alcohol,diluted, acetone, dichloromethane, ethyl acetate and dioxane respectively successively
Stock solution dilutes step by step, calculates detection limit with signal-to-noise ratio S/N >=3, quantitative limit is calculated with signal-to-noise ratio S/N >=10；
8. sample detection
Precision weighs polylactic acid-based guiding film 0.98g, is placed in ml headspace bottle, after dimethyl sulfoxide (DMSO) 5ml sealings are added, 80 DEG C
Heating water bath to polylactic acid-based guiding film is completely dissolved, and is cooled to room temperature as product to be tested solution, and sample introduction is balanced under the conditions of head space,
Record chromatogram；
Precision draws mixing reference substance stock solution 1ml, is placed in 10ml volumetric flasks, with dmso solution constant volume, makees
For mixed reference substance solution, 5ml mixed reference substance solutions is taken to be placed in ml headspace bottle, balances sample introduction under the conditions of sealing head space, record
Chromatogram, by external standard method with ethyl alcohol, acetone, dichloromethane, ethyl acetate, dioxy six in the polylactic acid-based guiding film of calculated by peak area
The content of ring is respectively 0.023%, 0.0029%, 0.00066%, 0.00025% and 0.0052%.
Embodiment 3
A method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film, using headspace gas chromatography,
Five kinds of ethyl alcohol in Bioabsorbable Polyesters film, acetone, dichloromethane, ethyl acetate and dioxane organic solvents are detected simultaneously,
The Bioabsorbable Polyesters film is polylactic acid-based guiding film；Specifically include following steps：
1. selected chromatographic condition：
Agilent 6890N gas chromatographs (fid detector), Agilent 7697A head-space samplers；
Chromatographic column：DB-624, specification are 30m × 0.530mm × 3.0 μm；
Column temperature：Temperature programming, 105 DEG C of initial temperature are kept 7min, are then warming up to the heating rate of 30 DEG C/min
7min is kept after 185 DEG C；
Injector temperature：210℃；
Detector temperature：260℃；
Carrier gas：Nitrogen, flow velocity 4.0mL/min；
Split ratio：15:1；
Head space equilibrium temperature：110 DEG C, equilibration time 40min；
Input mode：Headspace sampling mode, sample size 1mL.
2. the preparation of solution
The preparation of reference substance stock solution：Precision weighs ethyl alcohol 1.02g, acetone 1.02g, ethyl acetate 1.02g, adds two respectively
Simultaneously constant volume is in 100mL measuring bottles for methyl sulfoxide dissolving, as ethyl alcohol, acetoneand ethyl acetate reference substance stock solution；Take dichloromethane
Alkane 1.22g, dioxane 0.78g, accurately weighed, adding dmso solution respectively, simultaneously constant volume takes 10mL in 100mL measuring bottles
In 100mL measuring bottles, adds dmso solution respectively and constant volume is used as dichloromethane and dioxane pair in 100mL measuring bottles
According to product stock solution；
Mix the preparation of reference substance stock solution：
Precision weighs ethyl alcohol 1.02g, acetone 1.02g, ethyl acetate 1.02g and is placed in the first volumetric flask of 100ml, standby
With then precision weighs dichloromethane 1.22g again and dioxane 0.78g is placed in the second volumetric flask of 100ml, and diformazan is added
The dissolving of base sulfoxide and constant volume, take solution 10ml to be placed in the first volumetric flask, and it is molten that dimethyl sulfoxide (DMSO) is added into the first volumetric flask
Ethyl alcohol, acetoneand ethyl acetate are solved, mixing reference substance stock solution is obtained after constant volume.
Other operations are the same as embodiment 2.
By external standard method with ethyl alcohol in the polylactic acid-based guiding film of calculated by peak area (lot number 20170719), acetone, dichloromethane,
Ethyl acetate, dioxane content be respectively 0.031%, 0.0019%, 0.00075%, 0.00011% and 0.0059%.
Claims (6)
1. a kind of method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film, it is characterised in that：Using static headspace gas
Phase chromatography, while detecting five kinds of ethyl alcohol in Bioabsorbable Polyesters film, acetone, dichloromethane, ethyl acetate and dioxane
Organic solvent, the Bioabsorbable Polyesters film are polylactic acid-based guiding film；Specifically include following steps：
1. selected chromatographic condition：
Agilent 6890N gas chromatographs (fid detector), Agilent 7697A head-space samplers；
Chromatographic column：DB-624, specification are 30m × 0.530mm × 3.0 μm；
Column temperature：Temperature programming, 95~105 DEG C of initial temperature keep 4~7min, are then heated up with the heating rate of 30 DEG C/min
4~7min is kept after to 175~185 DEG C；
Injector temperature：195~210 DEG C；
Detector temperature：240~260 DEG C；
Carrier gas：Nitrogen, flow velocity are 2.0~4.0mL/min；
Split ratio：5~15:1；
Head space equilibrium temperature：95~110 DEG C, 20~40min of equilibration time；
Input mode：Headspace sampling mode, sample size 1mL；
2. the preparation of solution
The preparation of reference substance stock solution：Precision weigh 0.98~1.02g of ethyl alcohol, 0.98~1.02g of acetone, ethyl acetate 0.98~
1.02g adds dmso solution and constant volume is in 100mL measuring bottles, store as ethyl alcohol, acetoneand ethyl acetate reference substance respectively
Standby liquid；1.18~1.22g of dichloromethane, dioxane 0.74~0.78g are taken, it is accurately weighed, respectively plus dmso solution
And constant volume takes 10mL in 100mL measuring bottles in 100mL measuring bottles, adds dmso solution respectively and constant volume is in 100mL measuring bottles
It is middle to be used as dichloromethane and dioxane reference substance stock solution；
Mix the preparation of reference substance stock solution：
Precision weighs that 0.98~1.02g of ethyl alcohol, 0.98~1.02g of acetone, 0.98~1.02g of ethyl acetate are placed in 100ml
Spare in one volumetric flask, then precision weighs 1.18~1.22g of dichloromethane again and 0.74~0.78g of dioxane is placed in
In the second volumetric flask of 100ml, dmso solution and constant volume is added, solution 10ml is taken to be placed in the first volumetric flask, to
Dmso solution ethyl alcohol, acetoneand ethyl acetate are added in first volumetric flask, and mixing reference substance stock solution is obtained after constant volume；
3. system suitability
Take reference substance stock solution and the mixing reference substance stock solution of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane each
10ml is respectively placed in 100ml volumetric flasks, with dimethyl sulfoxide (DMSO) dilution and constant volume, respectively 5ml is taken to be placed in ml headspace bottle, sealed, top
Sample introduction is balanced under empty condition, records collection of illustrative plates；
4. precision test
Precision measures the reference substance stock solution 5ml of ethyl alcohol, acetone, dichloromethane, ethyl acetate and dioxane, is placed in 50ml appearances
It with dmso solution and constant volume in measuring bottle, takes 5mL in ml headspace bottle, seals, sample introduction, continuous sample introduction are balanced under the conditions of head space
6 times, record the relative standard deviation RSD of each reference substance；
5. linear test
By volume gradient, the accurate reference substance for measuring ethyl alcohol, acetone, ethyl acetate, dichloromethane and dioxane is storeed respectively
Liquid is respectively placed in same volume volumetric flask, is added dmso solution and constant volume, is prepared a series of linear test solution, so
It takes 5ml to be placed in ml headspace bottle respectively afterwards to seal, sample introduction is balanced under the conditions of head space, then with ethyl alcohol, acetone, ethyl acetate, dichloro
The peak area of the linear test solution of methane and dioxane is that ordinate establishes linear regression curves with a concentration of abscissa；
6. recovery test
3 parts of mixing reference substance stock solution is measured by volume gradient is accurate respectively, is respectively placed in same volume volumetric flask, uses dimethyl
Sulfoxide dissolving and constant volume, precision measure above-mentioned each solution 5ml, are placed in the 10ml ml headspace bottles equipped with 0.98~1.02g samples to be tested
In, sealing, heating water bath to sample to be tested is completely dissolved, is cooled to room temperature, and obtains the sample-adding solution of 3 concentration, each concentration
It is parallel to prepare 3 parts, sample introduction is balanced under the conditions of head space, calculates each component rate of recovery；
7. detection limit and quantitative limit experiment
Use the reference substance reserve of dimethyl sulfoxide (DMSO) alcohol,diluted, acetone, dichloromethane, ethyl acetate and dioxane respectively successively
Liquid dilutes step by step, calculates detection limit with signal-to-noise ratio S/N >=3, quantitative limit is calculated with signal-to-noise ratio S/N >=10；
8. sample detection
Precision weighs polylactic acid-based 0.98~1.02g of guiding film, is placed in ml headspace bottle, after dimethyl sulfoxide (DMSO) 5ml sealings are added, water
Bath is heated to polylactic acid-based guiding film and is completely dissolved, and is cooled to room temperature as product to be tested solution, balances sample introduction under the conditions of head space, remembers
Record chromatogram；
Precision draws mixing reference substance stock solution 1ml, is placed in 10ml volumetric flasks, with dmso solution constant volume, as mixed
Reference substance solution is closed, 5ml mixed reference substance solutions is taken to be placed in ml headspace bottle, sample introduction is balanced under the conditions of sealing head space, records chromatography
Figure, by external standard method with ethyl alcohol in the polylactic acid-based guiding film of calculated by peak area, acetone, dichloromethane, ethyl acetate, dioxane
Content.
2. the method for a variety of residual organic solvents, feature in detection Bioabsorbable Polyesters film according to claim 1
It is：Step 1. in select chromatographic condition be：
Column temperature：Temperature programming, 100 DEG C of initial temperature keep 5min, are then warming up to 180 DEG C with the heating rate of 30 DEG C/min
After keep 5min；
Injector temperature：200℃；
Detector temperature：250℃；
Carrier gas：Nitrogen, flow velocity 3.0mL/min；
Split ratio：10:1；
Head space equilibrium temperature：100 DEG C, equilibration time 30min.
3. the method for a variety of residual organic solvents, feature in detection Bioabsorbable Polyesters film according to claim 1
It is：Step 2. in the preparation process of reference substance stock solution be：
Take ethyl alcohol 1.00g, acetone 1.00g, ethyl acetate 1.00g, it is accurately weighed, respectively plus dmso solution and constant volume in
In 100mL measuring bottles, as ethyl alcohol, acetoneand ethyl acetate reference substance stock solution；Take dichloromethane 1.20g, dioxane
0.76g, it is accurately weighed, add dmso solution respectively and constant volume is in 100mL measuring bottles, takes 10mL in 100mL measuring bottles, point
Not plus dmso solution and constant volume are used as dichloromethane and dioxane reference substance stock solution in 100mL measuring bottles.
4. the method for a variety of residual organic solvents, feature in detection Bioabsorbable Polyesters film according to claim 3
It is：5. linear test is step：
The accurate reference substance stock solution 0.20ml for measuring ethyl alcohol, acetone, ethyl acetate, dichloromethane and dioxane of difference,
0.40ml, 0.60ml, 0.80ml, 1.00ml and 1.20ml are respectively placed in 10ml volumetric flasks, are added dmso solution and are determined
Hold, prepares a series of linear test solution.
5. the method for a variety of residual organic solvents, feature in detection Bioabsorbable Polyesters film according to claim 3
It is：6. recovery test is step：
It takes 0.80ml, 1.00ml and 1.20ml mixing reference substance stock solution to be respectively placed in 10ml volumetric flasks, it is sub- that dimethyl is added
Sulfone dissolving and constant volume, take the above-mentioned solution of 5ml to be placed in the ml headspace bottle equipped with the polylactic acid-based guiding films of 1.00g respectively, seal, 80 DEG C
Heating water bath to polylactic acid-based guiding film is completely dissolved, and is cooled to room temperature, and the sample-adding solution of 3 concentration is obtained, and each concentration is flat
Row prepares 3 parts, and sample introduction is balanced under the conditions of head space, calculates each component rate of recovery.
6. the method for a variety of residual organic solvents, feature in detection Bioabsorbable Polyesters film according to claim 3
It is：8. sample detection is step：
Precision weighs polylactic acid-based guiding film 1.00g, is placed in ml headspace bottle, and after dimethyl sulfoxide (DMSO) sealing is added, 80 DEG C of water-baths add
Heat to polylactic acid-based guiding film is completely dissolved, and is cooled to room temperature as product to be tested solution, then by product to be tested solution and ethyl alcohol, third
The mixed reference substance solution difference headspace sampling of ketone, dichloromethane, ethyl acetate and dioxane, records chromatogram, by external standard
Method is with the content of ethyl alcohol, acetone, dichloromethane, ethyl acetate, dioxane in the polylactic acid-based guiding film of calculated by peak area.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111458416A (en) * | 2019-01-18 | 2020-07-28 | 辽宁远大诺康生物制药有限公司 | Method for detecting impurities in poly (p-dioxanone) |
| CN113092607A (en) * | 2021-03-26 | 2021-07-09 | 山东省药学科学院 | Detection method for residual solvent in loratinib raw material medicine |
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| CN103487519A (en) * | 2013-09-05 | 2014-01-01 | 上海新亚药业有限公司 | Method for detecting multiple residual solvents in medicament |
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| CN103487519A (en) * | 2013-09-05 | 2014-01-01 | 上海新亚药业有限公司 | Method for detecting multiple residual solvents in medicament |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111458416A (en) * | 2019-01-18 | 2020-07-28 | 辽宁远大诺康生物制药有限公司 | Method for detecting impurities in poly (p-dioxanone) |
| CN111458416B (en) * | 2019-01-18 | 2022-08-09 | 沈阳恒生医用科技有限公司 | Method for detecting impurities in poly (p-dioxanone) |
| CN113092607A (en) * | 2021-03-26 | 2021-07-09 | 山东省药学科学院 | Detection method for residual solvent in loratinib raw material medicine |
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