CN108760951B - Method for detecting various residual organic solvents in bioabsorbable polyester film - Google Patents
Method for detecting various residual organic solvents in bioabsorbable polyester film Download PDFInfo
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Abstract
The invention discloses a method for detecting various residual organic solvents in a bioabsorbable polyester film, which adopts headspace gas chromatography to simultaneously detect five organic solvents, namely ethanol, acetone, dichloromethane, ethyl acetate and dioxane, in the bioabsorbable polyester film, and the detection method has the advantages of high sensitivity, good repeatability and high accuracy; because the external standard method is adopted, other standard substances are not needed to be used as internal standard substances, only pure substances of the components are needed to be detected, the requirement on the sampling precision is low, and the operation is simple; due to the adoption of the headspace gas chromatography, the interference of a polylactic acid product on detection is avoided, a gas instrument system cannot be polluted, and short-chain hydrocarbon micromolecule compounds generated after decomposition cannot interfere the detection result; the detection method can avoid the interference of small molecular impurities such as lactic acid, cyclic monomer and the like in the polylactic acid polymer material on dioxane, and can accurately detect the residual amount of the dioxane.
Description
Technical Field
The invention relates to the technical field of analysis and detection, in particular to a method for detecting various residual organic solvents in a bioabsorbable polyester film.
Background
Polylactic acid guide membranes are bioabsorbable polyester films, which are prepared from polylactic acid bioabsorbable polymers as raw materials through a special process, are used for Guiding Tissue Regeneration (GTR) or bone regeneration (GBR), and can be completely bioabsorbable without being taken out after the guiding action is finished, so that high safety is required. In addition, an organic solvent is inevitably used in the production process of raw materials and products, since the polylactic acid bio-absorbable polymer material is a mixed system of homologues with different molecular weights but not fixed molecular weights, in the production process of the polylactic acid bio-absorbable polymer material, in order to improve the uniformity of the molecular weight of the polymer material, an appropriate solvent is often selected for purification, and in the preparation process of the guide membrane, appropriate organic volatile matters are also used as the solvent or pore-forming agent, and since the volatile matters are probably not completely removed in later treatment, the use safety of the product is potentially dangerous, so that a method for accurately analyzing and detecting various residual solvents in the polylactic acid absorbable guide membrane is necessary.
The current detection method has the following defects: firstly, only one or two solvents of polylactic acid materials can be detected, and because the boiling points of small molecular impurities such as lactic acid, cyclic monomers and the like are close to the boiling point of dioxane, the detection of dioxane can be interfered by small molecules in a polylactic acid product, and the content of dioxane cannot be accurately detected by adopting the conventional method; secondly, the particularity of the polylactic acid material can interfere the detection of the solvent residue, because the decomposition temperature of the polylactic acid material is high, the polylactic acid polymer directly introduced into the polylactic acid material can pollute a gas phase instrument system such as a sample inlet, a liner tube, a chromatographic column and the like, and short-chain hydrocarbon micromolecule compounds can be generated after decomposition, which can interfere the detection; thirdly, according to the requirement of residual solvent content in the determination method of 0861 residual solvent specified in the pharmacopoeia 2015 edition of the people's republic of china and the raw materials and preparation process of the polylactic acid absorbable guide membrane, the residual amounts of ethanol (third solvent), acetone (third solvent), dichloromethane (second solvent), ethyl acetate (third solvent) and dioxane (second solvent) must be controlled to ensure the use safety of the polylactic acid absorbable guide membrane. The limit of ethanol, acetone and ethyl acetate is 0.5%, the limit of dichloromethane is 0.06% and the limit of dioxane is 0.038% in the 0861 residual solvent determination method according to the pharmacopoeia 2015 edition of the people's republic of China.
Disclosure of Invention
To solve the above problems, it is an object of the present invention to provide a method for detecting various residual organic solvents in a bioabsorbable polyester film.
In order to achieve the purpose, the invention is realized by the following technical scheme:
a method for detecting a plurality of residual organic solvents in a bioabsorbable polyester film simultaneously detects five organic solvents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the bioabsorbable polyester film by adopting a headspace gas chromatography, wherein the bioabsorbable polyester film is a polylactic acid guide film; the method specifically comprises the following steps:
selecting chromatographic conditions:
agilent 6890N gas chromatograph (FID detector), Agilent 7697A headspace sampler;
a chromatographic column: DB-624 with specification of 30m × 0.530mm × 3.0 μm;
column temperature: carrying out temperature programming, wherein the initial temperature is 95-105 ℃, keeping for 4-7 min, then heating to 175-185 ℃ at the heating rate of 30 ℃/min, and keeping for 4-7 min;
sample inlet temperature: 195-210 ℃;
detector temperature: 240-260 ℃;
carrier gas: nitrogen with the flow rate of 2.0-4.0 mL/min;
the split ratio is as follows: 5-15: 1;
headspace equilibrium temperature: the temperature is 95-110 ℃, and the balancing time is 20-40 min;
and (3) sample introduction mode: a headspace sample introduction mode is adopted, and the sample introduction amount is 1 mL;
preparation of solution
Preparation of a control stock solution: accurately weighing 0.98-1.02 g of ethanol, 0.98-1.02 g of acetone and 0.98-1.02 g of ethyl acetate, respectively adding dimethyl sulfoxide to dissolve the ethanol, the acetone and the ethyl acetate, and fixing the volume in a 100mL measuring flask to serve as reference substance storage solutions of the ethanol, the acetone and the ethyl acetate; taking 1.18-1.22 g of dichloromethane and 0.74-0.78 g of dioxane, precisely weighing, respectively adding dimethyl sulfoxide to dissolve and fix the volume in a 100mL measuring flask, taking 10mL of the solution in a 100mL measuring flask, respectively adding dimethyl sulfoxide to dissolve and fix the volume in the 100mL measuring flask to serve as dichloromethane and dioxane reference substance storage solutions;
preparation of mixed control stock solution:
accurately weighing 0.98-1.02 g of ethanol, 0.98-1.02 g of acetone and 0.98-1.02 g of ethyl acetate, placing the weighed materials in a first volumetric flask of 100ml for later use, then accurately weighing 1.18-1.22 g of dichloromethane and 0.74-0.78 g of dioxane, placing the weighed materials in a second volumetric flask of 100ml, adding dimethyl sulfoxide to dissolve and fix the volume, placing 10ml of the solution in a first volumetric flask, adding the dimethyl sulfoxide to dissolve the ethanol, the acetone and the ethyl acetate in the first volumetric flask, and fixing the volume to obtain a mixed reference substance storage solution;
third System suitability test
Respectively placing 10ml of reference substance stock solution and mixed reference substance stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane into 100ml volumetric flasks, diluting with dimethyl sulfoxide and fixing volume, placing 5ml of reference substance stock solution into a headspace flask, sealing, performing balanced sample injection under the headspace condition, and recording the map;
(iv) precision test
Precisely measuring 5mL of reference substance stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane, placing the reference substance stock solution into a 50mL volumetric flask, dissolving the reference substance stock solution by using dimethyl sulfoxide, fixing the volume, placing 5mL of the reference substance stock solution into a headspace bottle, sealing the headspace bottle, carrying out balanced sample injection for 6 times under the headspace condition, and recording the relative standard deviation RSD of each reference substance;
linear test
Precisely measuring reference substance storage solutions of ethanol, acetone, ethyl acetate, dichloromethane and dioxane according to volume gradient, respectively placing the reference substance storage solutions in volumetric flasks with the same volume, adding dimethyl sulfoxide to dissolve and fix the volume to prepare a series of linear test solutions, respectively placing 5ml of the linear test solutions in a headspace bottle to seal, carrying out balanced sample injection under the headspace condition, and establishing a linear regression curve by taking the peak areas of the linear test solutions of the ethanol, the acetone, the ethyl acetate, the dichloromethane and the dioxane as vertical coordinates and the concentration as horizontal coordinates;
recovery test
Precisely measuring 3 parts of mixed reference product stock solution according to volume gradient, respectively placing the mixed reference product stock solution into volumetric flasks with the same volume, dissolving by using dimethyl sulfoxide and fixing the volume, precisely measuring 5ml of each solution, placing the solution into a 10ml headspace flask containing 0.98-1.02 g of a sample to be detected, sealing, heating in a water bath until the sample to be detected is completely dissolved, cooling to room temperature to obtain sample adding solutions with 3 concentrations, preparing 3 parts of each concentration in parallel, carrying out balanced sample injection under a headspace condition, and calculating the recovery rate of each component;
test for detecting limit and quantifying limit
Sequentially and respectively diluting reference substance stock solutions of ethanol, acetone, dichloromethane, ethyl acetate and dioxane with dimethyl sulfoxide, gradually diluting, calculating detection limit with signal-to-noise ratio S/N being more than or equal to 3, and calculating quantification limit with signal-to-noise ratio S/N being more than or equal to 10;
detection of sample
Accurately weighing 0.98-1.02 g of polylactic acid guide membrane, placing the polylactic acid guide membrane in a headspace bottle, adding 5ml of dimethyl sulfoxide for sealing, heating in a water bath (the temperature is below 90 ℃) until the polylactic acid guide membrane is completely dissolved, cooling to room temperature to be used as a solution to be tested, carrying out balanced sample injection under the headspace condition, and recording a chromatogram;
precisely sucking 1ml of mixed reference substance storage solution, placing the mixed reference substance storage solution in a 10ml volumetric flask, dissolving dimethyl sulfoxide to a constant volume to obtain a mixed reference substance solution, placing 5ml of the mixed reference substance solution in a headspace flask, carrying out balanced sample injection under the condition of sealing the headspace, recording a chromatogram, and calculating the contents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the polylactic acid guide film by using a peak area according to an external standard method.
Preferably, the chromatographic conditions selected in step (i) are:
column temperature: column temperature: temperature programming is carried out, the initial temperature is 100 ℃, the temperature is kept for 5min, then the temperature is raised to 180 ℃ at the temperature raising rate of 30 ℃/min, and then the temperature is kept for 5 min;
sample inlet temperature: 200 ℃;
detector temperature: 250 ℃;
carrier gas: nitrogen with the flow rate of 3.0 mL/min;
the split ratio is as follows: 10: 1;
headspace equilibrium temperature: equilibration time 30min at 100 ℃.
Preferably, the preparation of the reference stock solution in the second step comprises the following steps:
precisely weighing 1.00g of ethanol, 1.00g of acetone and 1.00g of ethyl acetate, respectively adding dimethyl sulfoxide to dissolve and fix the volume in a 100mL measuring flask to serve as reference stock solutions of ethanol, acetone and ethyl acetate; 1.20g of dichloromethane and 0.76g of dioxane are precisely weighed, and are respectively dissolved in dimethyl sulfoxide and added with constant volume in a 100mL measuring flask, 10mL of the solution is added in the 100mL measuring flask, and the solution is respectively dissolved in dimethyl sulfoxide and added with constant volume in the 100mL measuring flask to serve as dichloromethane and dioxane reference substance storage solutions.
Preferably, the linear test of the step (c) is as follows:
accurately measuring reference substance stock solutions of ethanol, acetone, ethyl acetate, dichloromethane and dioxane to obtain 0.20ml, 0.40ml, 0.60ml, 0.80ml, 1.00ml and 1.20ml, respectively placing in 10ml volumetric flasks, adding dimethyl sulfoxide to dissolve and fix the volume, and preparing a series of linear test solutions.
Preferably, the recovery test comprises the following steps:
respectively placing 0.80ml, 1.00ml and 1.20ml of mixed reference stock solutions into a 10ml volumetric flask, adding dimethyl sulfoxide to dissolve and fix the volume, respectively placing 5ml of the solutions into a headspace flask filled with 1.00g of polylactic acid guide membrane, sealing, heating in a water bath at 80 ℃ until the polylactic acid guide membrane is completely dissolved, cooling to room temperature to obtain sample adding solutions with 3 concentrations, preparing 3 parts in parallel for each concentration, carrying out balanced sample injection under the headspace condition, and calculating the recovery rate of each component.
Preferably, the step of testing the sample is:
precisely weighing 1.00g of polylactic acid guide membrane, placing the polylactic acid guide membrane in a headspace bottle, adding dimethyl sulfoxide for sealing, heating in a water bath at 80 ℃ until the polylactic acid guide membrane is completely dissolved, cooling to room temperature to obtain a solution of a sample to be detected, respectively carrying out headspace sample injection on the solution of the sample to be detected and a reference sample stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane, recording a chromatogram, and calculating the contents of the ethanol, the acetone, the dichloromethane, the ethyl acetate and the dioxane in the polylactic acid guide membrane by using a peak area according to an external standard method.
Compared with the prior art, the invention has the following advantages:
according to the method for detecting various residual organic solvents in the bioabsorbable polyester film, five solvents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane can be detected simultaneously by adopting a headspace gas chromatography, and the method is high in sensitivity, good in repeatability and high in accuracy; because the external standard method is adopted, other standard substances are not needed to be used as internal standard substances, only pure substances of the components are needed to be detected, the requirement on the sampling precision is low, and the operation is simple; due to the adoption of the headspace gas chromatography, the interference of a polylactic acid product on detection is avoided, a gas instrument system cannot be polluted, and short-chain hydrocarbon micromolecule compounds generated after decomposition cannot interfere the detection result; the detection method can avoid the interference of small molecular impurities such as lactic acid, cyclic monomer and the like in the polylactic acid polymer material on dioxane, and can accurately detect the residual amount of the dioxane.
Drawings
FIG. 1 gas chromatogram for ethanol system suitability test (reference numeral 1. ethanol; 2. dimethyl sulfoxide);
FIG. 2 gas chromatogram for acetone system suitability test (reference numeral 1. acetone; 2. dimethyl sulfoxide);
FIG. 3 gas chromatogram for adaptability test of methylene chloride system (reference numeral 1. methylene chloride; 2. dimethyl sulfoxide);
FIG. 4 gas chromatogram for suitability test of ethyl acetate system (reference numeral 1. ethyl acetate; 2. dimethyl sulfoxide);
FIG. 5 gas chromatogram for suitability test of dioxane system (reference numeral 1. dioxane; 2. dimethyl sulfoxide);
FIG. 6 gas chromatogram for suitability test of ethanol, dichloromethane, acetone, ethyl acetate and dioxane mixing system (reference numeral 1. ethanol; 2. dichloromethane; 3. acetone; 4. ethyl acetate; 5. dioxane; 6. dimethyl sulfoxide).
Detailed Description
The invention is further described with reference to specific examples.
Example 1
A method for detecting a plurality of residual organic solvents in a bioabsorbable polyester film simultaneously detects five organic solvents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the bioabsorbable polyester film by adopting a headspace gas chromatography, wherein the bioabsorbable polyester film is a polylactic acid guide film; the method specifically comprises the following steps:
selecting chromatographic conditions:
the instrument comprises the following steps: agilent 6890N gas chromatograph (FID detector), Agilent 7697A headspace sampler; an Agilent chromatography workstation;
all the reagents are chromatographically pure, polylactic acid guides bone regeneration membrane (batch No. 20170112);
a chromatographic column: DB-624 with specification of 30m × 0.530mm × 3.0 μm;
column temperature: temperature programming is carried out, the initial temperature is 100 ℃, the temperature is kept for 5min, then the temperature is raised to 180 ℃ at the temperature raising rate of 30 ℃/min, and then the temperature is kept for 5 min;
sample inlet temperature: 200 ℃;
detector temperature: 250 ℃;
carrier gas: nitrogen with the flow rate of 3.0 mL/min;
the split ratio is as follows: 10: 1;
headspace equilibrium temperature: balancing for 30min at 100 ℃;
and (3) sample introduction mode: a headspace sample introduction mode is adopted, and the sample introduction amount is 1 mL;
preparation of solution
Preparation of a control stock solution: accurately weighing 1.00g of ethanol, 1.00g of acetone and 1.00g of ethyl acetate, respectively adding dimethyl sulfoxide to dissolve the ethanol, the acetone and the ethyl acetate, and fixing the volume in a 100mL measuring flask to be used as reference substance stock solutions of the ethanol, the acetone and the ethyl acetate; taking 1.20g of dichloromethane and 0.76g of dioxane, precisely weighing, respectively adding dimethyl sulfoxide to dissolve and fix the volume in a 100mL measuring flask, taking 10mL in the 100mL measuring flask, respectively adding dimethyl sulfoxide to dissolve and fix the volume in the 100mL measuring flask to serve as dichloromethane and dioxane reference substance storage solutions;
preparation of mixed control stock solution:
accurately weighing 1.00g of ethanol, 1.00g of acetone and 1.00g of ethyl acetate, placing the ethanol, the acetone and the ethyl acetate into a first volumetric flask of 100ml for later use, then accurately weighing 1.20g of dichloromethane and 0.76g of dioxane, placing the dichloromethane and the dioxane into a second volumetric flask of 100ml, adding dimethyl sulfoxide to dissolve and fix the volume, placing 10ml of the solution into a first volumetric flask, adding the dimethyl sulfoxide into the first volumetric flask to dissolve the ethanol, the acetone and the ethyl acetate, and fixing the volume to obtain a mixed reference stock solution;
third System suitability test
Respectively placing 10ml of reference substance stock solution and mixed reference substance stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane into 100ml volumetric flasks, diluting with dimethyl sulfoxide and fixing volume, placing 5ml of reference substance stock solution into a headspace flask, sealing, performing balanced sample injection under the headspace condition, and recording the map; the retention time and separation results of each component are shown in table 1, and the system adaptability profiles of each component are shown in fig. 1-6.
TABLE 1 retention time and separation results for each component
(iv) precision test
Precisely measuring 5mL of reference substance stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane, placing the reference substance stock solution into a 50mL volumetric flask, dissolving the reference substance stock solution by using dimethyl sulfoxide, fixing the volume, taking 5mL of the reference substance stock solution into a headspace bottle, sealing the headspace bottle, carrying out balanced sample injection for 6 times under the headspace condition, and recording the relative standard deviation RSD of each reference substance, wherein the RSD value of each component is within 5% as shown in a table 2.
Table 2 RSD results table for each control (n ═ 6)
Linear test
Respectively and precisely measuring 0.20ml, 0.40ml, 0.60ml, 0.80ml, 1.00ml and 1.20ml of reference substance stock solutions of ethanol, acetone, ethyl acetate, dichloromethane and dioxane, respectively placing the reference substance stock solutions into a 10ml volumetric flask, adding dimethyl sulfoxide for dissolving and fixing the volume to prepare a series of linear test solutions, respectively placing 5ml of the linear test solutions into a headspace flask for sealing, carrying out balanced sample injection under the headspace condition, establishing a linear regression curve by taking the peak areas of the linear test solutions of the ethanol, the acetone, the ethyl acetate, the dichloromethane and the dioxane as vertical coordinates and the concentrations as horizontal coordinates, and obtaining the results shown in Table 3.
TABLE 3 results of the Linear test
Recovery test
Respectively placing 0.80ml, 1.00ml and 1.20ml of mixed reference stock solutions into a 10ml volumetric flask, adding dimethyl sulfoxide to dissolve and fix the volume, respectively placing 5ml of the solutions into a headspace flask containing 1g of polylactic acid guide membrane, sealing, heating in water bath until the polylactic acid guide membrane is completely dissolved, cooling to room temperature at the water bath temperature below 90 ℃ to obtain 3 sample adding solutions with 3 concentrations, preparing 3 parts in parallel for each concentration, carrying out balanced sample injection under headspace conditions, and calculating the recovery rate of each component, wherein the results are shown in Table 4.
TABLE 4 recovery test results
Test for detecting limit and quantifying limit
Sequentially and respectively diluting reference substance stock solutions of ethanol, acetone, dichloromethane, ethyl acetate and dioxane with dimethyl sulfoxide, gradually diluting, calculating detection limit with signal-to-noise ratio S/N being more than or equal to 3, and calculating quantification limit with signal-to-noise ratio S/N being more than or equal to 10; respectively taking 5mL of the sample, sealing the sample in a headspace bottle, carrying out balanced sample injection under the headspace condition, and recording a chromatogram. The results of the detection limit and the quantification limit are shown in Table 5.
TABLE 5 detection limit and quantitation limit results for each component
Detection of sample
Precisely weighing 1.00g of polylactic acid guide membrane, placing the polylactic acid guide membrane in a headspace bottle, adding 5ml of dimethyl sulfoxide, sealing, heating in a water bath until the polylactic acid guide membrane is completely dissolved, wherein the water bath temperature is generally below 90 ℃, the optimal temperature is 80 ℃, cooling to room temperature to be used as a solution of a sample to be tested, carrying out balanced sample injection under the headspace condition, and recording a chromatogram;
precisely sucking 1ml of mixed reference substance storage solution, placing the mixed reference substance storage solution in a 10ml volumetric flask, dissolving dimethyl sulfoxide to a constant volume to obtain a mixed reference substance solution, placing 5ml of the mixed reference substance solution in a headspace flask, carrying out balanced sample injection under the condition of sealing the headspace, recording a chromatogram, and calculating the contents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the polylactic acid guide film by using a peak area according to an external standard method. According to the limit requirement of common residual solvents in the pharmacopoeia of the people's republic of China 2015 edition, ethanol is not more than 0.5 percent, acetone is not more than 0.5 percent, dichloromethane is not more than 0.06 percent, ethyl acetate is not more than 0.5 percent, and dioxane is not more than 0.038 percent.
The method for detecting the residual quantity of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the sample comprises the following steps: 0.019%, 0.0021%, 0.00057%, 0.00014% and 0.0045%, and the residual amounts of the five solvents all meet the safety limit requirements of pharmacopoeia of the people's republic of China.
Example 2
A method for detecting a plurality of residual organic solvents in a bioabsorbable polyester film simultaneously detects five organic solvents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the bioabsorbable polyester film by adopting a headspace gas chromatography, wherein the bioabsorbable polyester film is a polylactic acid guide film; the method specifically comprises the following steps:
selecting chromatographic conditions:
the instrument comprises the following steps: agilent 6890N gas chromatograph (FID detector), Agilent 7697A headspace sampler; an Agilent chromatography workstation;
reagent: all the reagents are chromatographically pure; polylactic acid absorbable guided bone regeneration membrane (lot No. 20170517);
a chromatographic column: DB-624 with specification of 30m × 0.530mm × 3.0 μm;
column temperature: temperature programming is carried out, the initial temperature is 95 ℃, the temperature is kept for 4min, then the temperature is raised to 175 ℃ at the temperature raising rate of 30 ℃/min, and then the temperature is kept for 4 min;
sample inlet temperature: 195 ℃;
detector temperature: 240 ℃;
carrier gas: nitrogen with the flow rate of 2.0 mL/min;
the split ratio is as follows: 5: 1;
headspace equilibrium temperature: equilibrating at 95 deg.C for 20 min;
and (3) sample introduction mode: a headspace sample introduction mode is adopted, and the sample introduction amount is 1 mL;
preparation of solution
Preparation of a control stock solution: accurately weighing 0.98g of ethanol, 0.98g of acetone and 0.98g of ethyl acetate, respectively adding dimethyl sulfoxide to dissolve, and fixing the volume in a 100mL measuring flask to obtain ethanol, acetone and ethyl acetate reference substance stock solutions; taking 1.18g of dichloromethane and 0.74g of dioxane, precisely weighing, respectively adding dimethyl sulfoxide to dissolve and fix the volume in a 100mL measuring flask, taking 10mL in the 100mL measuring flask, respectively adding dimethyl sulfoxide to dissolve and fix the volume in the 100mL measuring flask to serve as dichloromethane and dioxane reference substance storage solutions;
preparation of mixed control stock solution:
accurately weighing 0.98g of ethanol, 0.98g of acetone and 0.98g of ethyl acetate, placing the weighed materials in a first volumetric flask of 100ml for later use, then accurately weighing 1.18g of dichloromethane and 0.74g of dioxane, placing the weighed materials in a second volumetric flask of 100ml, adding dimethyl sulfoxide to dissolve and fix the volume, placing 10ml of the solution in a first volumetric flask, adding dimethyl sulfoxide to the first volumetric flask to dissolve ethanol, acetone and ethyl acetate, and fixing the volume to obtain a mixed reference stock solution;
third System suitability test
Respectively placing 10ml of reference substance stock solution and mixed reference substance stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane into 100ml volumetric flasks, diluting with dimethyl sulfoxide and fixing volume, placing 5ml of reference substance stock solution into a headspace flask, sealing, performing balanced sample injection under the headspace condition, and recording the map;
(iv) precision test
Precisely measuring 5mL of reference substance storage solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane, placing the reference substance storage solution in a 50mL volumetric flask, dissolving the reference substance storage solution by using dimethyl sulfoxide, fixing the volume, placing 5mL in a headspace bottle, sealing, carrying out balanced sample injection under the headspace condition, carrying out continuous sample injection for 6 times, carrying out headspace sample injection, and recording the relative standard deviation RSD of each reference substance;
linear test
Precisely measuring reference substance storage solutions of ethanol, acetone, ethyl acetate, dichloromethane and dioxane according to volume gradient, respectively placing the reference substance storage solutions into volumetric flasks with the same volume, adding dimethyl sulfoxide to dissolve and fix the volume to prepare a series of linear test solutions, respectively placing 5ml of the linear test solutions into a headspace bottle to seal, carrying out balanced sample injection under a headspace condition, and establishing a linear regression curve by taking the peak areas of the linear test solutions of the ethanol, the acetone, the ethyl acetate, the dichloromethane and the dioxane as vertical coordinates and the concentrations as horizontal coordinates;
recovery test
Precisely measuring 3 parts of mixed reference product stock solution according to volume gradient, respectively placing the mixed reference product stock solution into volumetric flasks with the same volume, dissolving by using dimethyl sulfoxide and fixing the volume, precisely measuring 5ml of each solution, placing the solution into a 10ml headspace flask containing 0.98g of a sample to be detected, sealing, heating in a water bath at 80 ℃ until the sample to be detected is completely dissolved, cooling to room temperature to obtain sample adding solutions with 3 concentrations, preparing 3 parts of each concentration in parallel, carrying out balanced sample injection under the headspace condition, and calculating the recovery rate of each component;
test for detecting limit and quantifying limit
Sequentially and respectively diluting reference substance stock solutions of ethanol, acetone, dichloromethane, ethyl acetate and dioxane with dimethyl sulfoxide, gradually diluting, calculating detection limit with signal-to-noise ratio S/N being more than or equal to 3, and calculating quantification limit with signal-to-noise ratio S/N being more than or equal to 10;
detection of sample
Accurately weighing 0.98g of polylactic acid guide membrane, placing the polylactic acid guide membrane in a headspace bottle, adding 5ml of dimethyl sulfoxide, sealing, heating in a water bath at 80 ℃ until the polylactic acid guide membrane is completely dissolved, cooling to room temperature to obtain a solution to be measured, carrying out balanced sample injection under the headspace condition, and recording a chromatogram;
precisely sucking 1ml of mixed reference stock solution, placing the mixed reference stock solution in a 10ml volumetric flask, dissolving dimethyl sulfoxide to a constant volume to obtain a mixed reference solution, placing 5ml of the mixed reference solution in a headspace flask, carrying out balanced sample injection under the condition of sealing the headspace, recording a chromatogram, and calculating the contents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the polylactic acid guide film respectively to be 0.023%, 0.0029%, 0.00066%, 0.00025% and 0.0052% by using a peak area according to an external standard method.
Example 3
A method for detecting a plurality of residual organic solvents in a bioabsorbable polyester film simultaneously detects five organic solvents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the bioabsorbable polyester film by adopting a headspace gas chromatography, wherein the bioabsorbable polyester film is a polylactic acid guide film; the method specifically comprises the following steps:
selecting chromatographic conditions:
agilent 6890N gas chromatograph (FID detector), Agilent 7697A headspace sampler;
a chromatographic column: DB-624 with specification of 30m × 0.530mm × 3.0 μm;
column temperature: temperature programming is carried out, the initial temperature is 105 ℃, the temperature is kept for 7min, then the temperature is raised to 185 ℃ at the temperature raising rate of 30 ℃/min, and then the temperature is kept for 7 min;
sample inlet temperature: at 210 ℃;
detector temperature: 260 ℃;
carrier gas: nitrogen with the flow rate of 4.0 mL/min;
the split ratio is as follows: 15: 1;
headspace equilibrium temperature: keeping the temperature at 110 ℃ for 40 min;
and (3) sample introduction mode: and (4) adopting a headspace sample introduction mode, wherein the sample introduction amount is 1 mL.
Preparation of solution
Preparation of a control stock solution: accurately weighing 1.02g of ethanol, 1.02g of acetone and 1.02g of ethyl acetate, respectively adding dimethyl sulfoxide to dissolve the ethanol, the acetone and the ethyl acetate, and fixing the volume in a 100mL measuring flask to be used as reference substance storage solutions of the ethanol, the acetone and the ethyl acetate; taking 1.22g of dichloromethane and 0.78g of dioxane, precisely weighing, respectively adding dimethyl sulfoxide to dissolve and fix the volume in a 100mL measuring flask, taking 10mL in a 100mL measuring flask, respectively adding dimethyl sulfoxide to dissolve and fix the volume in the 100mL measuring flask to serve as dichloromethane and dioxane reference substance storage solutions;
preparation of mixed control stock solution:
accurately weighing 1.02g of ethanol, 1.02g of acetone and 1.02g of ethyl acetate, placing the weighed materials in a first volumetric flask of 100ml for later use, then accurately weighing 1.22g of dichloromethane and 0.78g of dioxane, placing the weighed materials in a second volumetric flask of 100ml, adding dimethyl sulfoxide to dissolve and fix the volume, placing 10ml of the solution in a first volumetric flask, adding dimethyl sulfoxide to the first volumetric flask to dissolve ethanol, acetone and ethyl acetate, and fixing the volume to obtain a mixed reference substance storage solution.
The other operations were the same as in example 2.
The contents of ethanol, acetone, methylene chloride, ethyl acetate, and dioxane in the polylactic acid based guide film (run No. 20170719) were 0.031%, 0.0019%, 0.00075%, 0.00011%, and 0.0059%, respectively, as calculated by peak area according to the external standard method.
Claims (5)
1. A method of detecting a plurality of residual organic solvents in a bioabsorbable polyester film, comprising: simultaneously detecting five organic solvents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in a bioabsorbable polyester film by adopting a headspace gas chromatography, wherein the bioabsorbable polyester film is a polylactic acid guide film; the method specifically comprises the following steps:
selecting chromatographic conditions:
agilent 6890N gas chromatograph, FID detector, Agilent 7697A headspace sampler;
a chromatographic column: DB-624 with specification of 30m × 0.530mm × 3.0 μm;
column temperature: temperature programming is carried out, the initial temperature is 100 ℃, the temperature is kept for 5min, then the temperature is raised to 180 ℃ at the temperature raising rate of 30 ℃/min, and then the temperature is kept for 5 min;
sample inlet temperature: 200 ℃;
detector temperature: 250 ℃;
carrier gas: nitrogen with the flow rate of 3.0 mL/min;
the split ratio is as follows: 10: 1;
headspace equilibrium temperature: balancing for 30min at 100 ℃;
and (3) sample introduction mode: a headspace sample introduction mode is adopted, and the sample introduction amount is 1 mL;
preparation of solution
Preparation of a control stock solution: accurately weighing 0.98-1.02 g of ethanol, 0.98-1.02 g of acetone and 0.98-1.02 g of ethyl acetate, respectively adding dimethyl sulfoxide to dissolve the ethanol, the acetone and the ethyl acetate, and fixing the volume in a 100mL measuring flask to serve as reference substance storage solutions of the ethanol, the acetone and the ethyl acetate; taking 1.18-1.22 g of dichloromethane and 0.74-0.78 g of dioxane, precisely weighing, respectively adding dimethyl sulfoxide to dissolve and fix the volume in a 100mL measuring flask, taking 10mL of the solution in a 100mL measuring flask, respectively adding dimethyl sulfoxide to dissolve and fix the volume in the 100mL measuring flask to serve as dichloromethane and dioxane reference substance storage solutions;
preparation of mixed control stock solution:
accurately weighing 0.98-1.02 g of ethanol, 0.98-1.02 g of acetone and 0.98-1.02 g of ethyl acetate, placing the weighed materials in a first volumetric flask of 100ml for later use, then accurately weighing 1.18-1.22 g of dichloromethane and 0.74-0.78 g of dioxane, placing the weighed materials in a second volumetric flask of 100ml, adding dimethyl sulfoxide to dissolve and fix the volume, placing 10ml of the solution in a first volumetric flask, adding the dimethyl sulfoxide to dissolve the ethanol, the acetone and the ethyl acetate in the first volumetric flask, and fixing the volume to obtain a mixed reference substance storage solution;
third System suitability test
Respectively placing 10ml of reference substance stock solution and mixed reference substance stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane into 100ml volumetric flasks, diluting with dimethyl sulfoxide and fixing volume, placing 5ml of reference substance stock solution into a headspace flask, sealing, performing balanced sample injection under the headspace condition, and recording the map;
(iv) precision test
Precisely measuring 5mL of reference substance stock solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane, placing the reference substance stock solution into a 50mL volumetric flask, dissolving the reference substance stock solution by using dimethyl sulfoxide, fixing the volume, placing 5mL of the reference substance stock solution into a headspace bottle, sealing the headspace bottle, carrying out balanced sample injection for 6 times under the headspace condition, and recording the relative standard deviation RSD of each reference substance;
linear test
Precisely measuring reference substance storage solutions of ethanol, acetone, ethyl acetate, dichloromethane and dioxane according to volume gradient, respectively placing the reference substance storage solutions into volumetric flasks with the same volume, adding dimethyl sulfoxide to dissolve and fix the volume to prepare a series of linear test solutions, respectively placing 5ml of the linear test solutions into a headspace bottle to seal, carrying out balanced sample injection under a headspace condition, and establishing a linear regression curve by taking the peak areas of the linear test solutions of the ethanol, the acetone, the ethyl acetate, the dichloromethane and the dioxane as vertical coordinates and the concentrations as horizontal coordinates;
recovery test
Precisely measuring 3 parts of mixed reference product stock solution according to volume gradient, respectively placing the mixed reference product stock solution into volumetric flasks with the same volume, dissolving by using dimethyl sulfoxide and fixing the volume, precisely measuring 5ml of each solution, placing the solution into a 10ml headspace flask containing 0.98-1.02 g of a sample to be detected, sealing, heating in a water bath until the sample to be detected is completely dissolved, cooling to room temperature to obtain sample adding solutions with 3 concentrations, preparing 3 parts of each concentration in parallel, carrying out balanced sample injection under a headspace condition, and calculating the recovery rate of each component;
test for detecting limit and quantifying limit
Sequentially and respectively diluting reference substance stock solutions of ethanol, acetone, dichloromethane, ethyl acetate and dioxane with dimethyl sulfoxide, gradually diluting, calculating detection limit with signal-to-noise ratio S/N being more than or equal to 3, and calculating quantification limit with signal-to-noise ratio S/N being more than or equal to 10;
detection of sample
Accurately weighing 0.98-1.02 g of polylactic acid guide membrane, placing the polylactic acid guide membrane in a headspace bottle, adding 5ml of dimethyl sulfoxide for sealing, heating in a water bath until the polylactic acid guide membrane is completely dissolved, cooling to room temperature to be used as a solution to be tested, carrying out balanced sample injection under the headspace condition, and recording a chromatogram;
precisely sucking 1ml of mixed reference substance storage solution, placing the mixed reference substance storage solution in a 10ml volumetric flask, dissolving dimethyl sulfoxide to a constant volume to obtain a mixed reference substance solution, placing 5ml of the mixed reference substance solution in a headspace flask, carrying out balanced sample injection under the condition of sealing the headspace, recording a chromatogram, and calculating the contents of ethanol, acetone, dichloromethane, ethyl acetate and dioxane in the polylactic acid guide film by using a peak area according to an external standard method.
2. The method of detecting multiple residual organic solvents in a bioabsorbable polyester film of claim 1, wherein: the preparation of the reference substance storage solution in the step II comprises the following steps:
precisely weighing 1.00g of ethanol, 1.00g of acetone and 1.00g of ethyl acetate, respectively adding dimethyl sulfoxide to dissolve and fix the volume in a 100mL measuring flask to serve as reference stock solutions of ethanol, acetone and ethyl acetate; 1.20g of dichloromethane and 0.76g of dioxane are precisely weighed, and are respectively dissolved in dimethyl sulfoxide and added with constant volume in a 100mL measuring flask, 10mL of the solution is added in the 100mL measuring flask, and the solution is respectively dissolved in dimethyl sulfoxide and added with constant volume in the 100mL measuring flask to serve as dichloromethane and dioxane reference substance storage solutions.
3. The method of detecting a plurality of residual organic solvents in a bioabsorbable polyester film of claim 2, wherein: the linear test is as follows:
accurately measuring reference substance stock solutions of ethanol, acetone, ethyl acetate, dichloromethane and dioxane to obtain 0.20ml, 0.40ml, 0.60ml, 0.80ml, 1.00ml and 1.20ml, respectively placing in 10ml volumetric flasks, adding dimethyl sulfoxide to dissolve and fix the volume, and preparing a series of linear test solutions.
4. The method of detecting a plurality of residual organic solvents in a bioabsorbable polyester film of claim 2, wherein: step sixthly, the recovery rate test is as follows:
respectively placing 0.80ml, 1.00ml and 1.20ml of mixed reference stock solutions into a 10ml volumetric flask, adding dimethyl sulfoxide to dissolve and fix the volume, respectively placing 5ml of the solutions into a headspace flask filled with 1.00g of polylactic acid guide membrane, sealing, heating in a water bath at 80 ℃ until the polylactic acid guide membrane is completely dissolved, cooling to room temperature to obtain sample adding solutions with 3 concentrations, preparing 3 parts in parallel for each concentration, carrying out balanced sample injection under the headspace condition, and calculating the recovery rate of each component.
5. The method of detecting a plurality of residual organic solvents in a bioabsorbable polyester film of claim 2, wherein: step eight, sample detection:
precisely weighing 1.00g of polylactic acid guide membrane, placing the polylactic acid guide membrane in a headspace bottle, adding dimethyl sulfoxide for sealing, heating in a water bath at 80 ℃ until the polylactic acid guide membrane is completely dissolved, cooling to room temperature to obtain a solution of a to-be-detected product, respectively carrying out headspace sample injection on the solution of the to-be-detected product and a mixed reference product solution of ethanol, acetone, dichloromethane, ethyl acetate and dioxane, recording a chromatogram, and calculating the contents of the ethanol, the acetone, the dichloromethane, the ethyl acetate and the dioxane in the polylactic acid guide membrane by using a peak area according to an external standard method.
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