Method for determining residual monomers of polyglycolic acid

Abstract

The invention provides a polyglycolic acid residual monomer determination method, and belongs to the technical field of coal chemical industry determination, and the method comprises the following steps: carrying out low temperature embrittlement and crushing pretreatment on a polyglycolic acid sample; dissolving the pretreated polyglycolic acid sample in a hexafluoroisopropanol reagent to obtain a dissolved sample; preparing an internal standard substance with the mass concentration of 0.5-5% by using a 4-chlorobenzophenone reagent and an acetone reagent; mixing the internal standard substance with the dissolved sample, separating out and filtering to obtain a to-be-analyzed sample; presetting a standard solution in a gas chromatograph, and establishing an internal standard method curve; a to-be-analyzed sample is placed in a sample injection bottle, and chromatographic analysis and data processing are performed on the to-be-analyzed sample through a gas chromatograph internal standard method to obtain a chromatogram, residual sheet data, an average relative error and a relative standard deviation. The polyglycolic acid residual monomer determination method provided by the invention is simple and efficient, and the determination accuracy is relatively high.

Description

Technical Field

[0001] The present invention relates to the technical field of coal chemical industry determination, in particular to a method for determining polyglycolic acid residues. Background Art

[0002] Polyglycolic acid (PGA) is an aliphatic polyester polymer material with the least carbon number per unit, a completely decomposable ester structure, and the fastest degradation rate. It is a polymer compound formed by the polymerization of glycolide.

[0003] Residual polyglycolic acid refers to the content of glycolide (GL) monomer remaining in polyglycolic acid (PGA) samples, expressed as a mass percentage (unit: %). During the production of polyglycolic acid in the coal chemical industry, the glycolide content in polyglycolic acid needs to be measured. This is used to analyze whether the production equipment of polyglycolic acid is running smoothly, whether its production process parameters need to be optimized and adjusted, and whether the monitoring process of the polymerization reaction is in place, so as to determine whether the quality of the end product meets the requirements.

[0004] However, there is currently no relevant national standard to follow for the determination of polyglycolic acid (PGA) residues, and the determination of polyglycolic acid (PGA) residues is still in a technical blank in the coal chemical industry and the field of coal-based biodegradable materials.

[0005] Therefore, it is necessary to provide a method for determining polyglycolic acid residues that is simple, efficient, and has high accuracy. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a method for determining polyglycolic acid residues which is simple, efficient and has high determination accuracy.

[0007] To solve the above technical problems, the present invention provides a method for determining the content of residual glycolide monomer in a polyglycolic acid sample, which comprises the following steps:

[0008] Pretreatment of polyglycolic acid samples for low-temperature embrittlement and crushing;

[0009] The pretreated polyglycolic acid sample is dissolved in hexafluoroisopropanol reagent to obtain a dissolved sample;

[0010] An internal standard with a mass concentration of 0.5-5% is prepared using 4-chlorobenzophenone reagent and acetone reagent;

[0011] The internal standard substance is mixed with the dissolved sample, and then precipitated and filtered to obtain a sample to be analyzed;

[0012] Preset the standard solution in the gas chromatograph to establish the internal standard curve;

[0013] The sample to be analyzed is placed in an injection bottle, and the sample to be analyzed is chromatographically analyzed and the data is processed by the internal standard method of gas chromatography to obtain the chromatogram, residual data, average relative error and relative standard deviation.

[0014] Furthermore, the polyglycolic acid sample pretreatment step includes:

[0015] Place the polyglycolic acid sample in a sample cup and add liquid nitrogen until the sample is completely covered to embrittle the sample at low temperature;

[0016] The embrittled polyglycolic acid sample is crushed in a crusher to obtain a granular or / and powdered polyglycolic acid sample.

[0017] Furthermore, the step of dissolving the pretreated polyglycolic acid sample in a hexafluoroisopropanol reagent to dissolve the sample comprises:

[0018] Take a pretreated polyglycolic acid sample with a mass of m1 and put it into a sample dissolution bottle;

[0019] Add hexafluoroisopropanol reagent with a volume of V1 to the sample dissolution bottle;

[0020] The sample dissolving bottle is placed on a polymer dissolver to dissolve the pretreated polyglycolic acid sample to obtain a dissolved sample.

[0021] Furthermore, the dissolution temperature of the polymer dissolver is set to 25-59° C., and the stirring speed of the polymer dissolver is set to 50-600 rpm.

[0022] Furthermore, the step of preparing an internal standard with a mass concentration of 0.5-5% using a 4-chlorobenzophenone reagent and an acetone reagent comprises:

[0023] 4-Chlorobenzophenone reagent m2 and acetone reagent m3 are prepared respectively in a mass ratio of 1:19-1:199;

[0024] Add the 4-chlorobenzophenone reagent m2 and the acetone reagent m3 into a screw-capped sample bottle and mix them evenly to obtain an internal standard with a mass concentration of 0.5-5%.

[0025] Furthermore, the steps of mixing the internal standard with the dissolved sample, precipitating and filtering to obtain the sample to be analyzed include:

[0026] Take the internal standard substance of mass m4 and put it into the sample dissolution bottle;

[0027] Add volume V2 of acetone reagent to the sample dissolution bottle and mix until the mixture becomes white and turbid;

[0028] After the precipitation is complete, the mixed solution is filtered with a syringe filter to obtain the sample to be analyzed.

[0029] Furthermore, the standard solution comprises:

[0030] Glycolide, mass 0.0012g;

[0031] Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g);

[0032] Weigh 0.1004 g of the internal standard with a concentration of 1.0052%;

[0033] Acetone, volume 5ml;

[0034] Hexafluoroisopropanol, volume 10 ml;

[0035] The mass of 4-chlorobenzophenone in the standard solution is 0.0010.

[0036] Furthermore, the standard solution comprises:

[0037] glycolide, mass 0.0024 g;

[0038] Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g);

[0039] Weigh 0.1085 g of the internal standard with a concentration of 1.0052%;

[0040] Acetone, volume 5ml;

[0041] Hexafluoroisopropanol, volume 10 ml;

[0042] The mass of 4-chlorobenzophenone in the standard solution is 0.0011.

[0043] Furthermore, the standard solution comprises:

[0044] glycolide, mass 0.0062g;

[0045] Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g);

[0046] Weigh 0.1105 g of the internal standard with a concentration of 1.0052%;

[0047] Acetone, volume 5ml;

[0048] Hexafluoroisopropanol, volume 10 ml;

[0049] The mass of 4-chlorobenzophenone in the standard solution is 0.0011.

[0050] Furthermore, the crushing time is ≤1 min.

[0051] The present invention provides a method for determining residual monomers in polyglycolic acid, which can accurately determine the content of residual glycolide monomer in a polyglycolic acid sample, thereby enabling accurate analysis of the residual monomers in the polyglycolic acid sample, ensuring the smooth operation of a production device, providing a reference basis for optimizing and adjusting process parameters, and efficiently assisting in process monitoring of polymerization reactions. This plays a vital role in quality judgment of end products and comparative procurement by downstream manufacturers, and is also directly related to the market prospects and market share of subsequent promotion of polyglycolic acid products, playing a decisive role and providing guiding significance.

[0052] Furthermore, the present invention provides a method for determining polyglycolic acid residues, which pre-treats the polyglycolic acid sample by low-temperature embrittlement and crushing, thereby increasing the contact area between the sample and the organic solvent, accelerating its dissolution, shortening the analysis time, and thus improving the determination efficiency.

[0053] At the same time, the present invention provides a method for determining the residual monomers of polyglycolic acid, which uses hexafluoroisopropanol reagent as a dissolving reagent, and can completely dissolve the residual glycolide monomer in the polyglycolic acid sample, thereby ensuring the accuracy of the determination of the residual monomers of polyglycolic acid, and also ensuring the representativeness and integrity of the determination of the polyglycolic acid sample. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 A flow chart of a method for determining polyglycolic acid residues provided in an embodiment of the present invention;

[0055] Figure 2 This is a chromatogram of the residual monomers of a polyglycolic acid sample in the method for determining the residual monomers of polyglycolic acid provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0056] See also Figure 1 The present invention provides a method for determining the residual glycolide monomer in a polyglycolic acid sample. This method utilizes an internal standard method for quantification. 4-Chlorobenzophenone is added to the polyglycolic acid sample as an internal standard. Both are then introduced into a gas chromatograph. The mass fraction of the glycolide monomer can be calculated using the internal standard method based on the peak area of the glycolide monomer, the peak area of the internal standard, and the mass of the internal standard in the chromatogram. The method specifically includes the following steps:

[0057] Step 1) Pretreatment of the polyglycolic acid sample for low-temperature embrittlement and crushing.

[0058] The pretreatment steps of the polyglycolic acid sample include:

[0059] First, place the polyglycolic acid sample in a sample cup and add liquid nitrogen until the sample is completely covered to embrittle the sample at low temperature.

[0060] The embrittled polyglycolic acid sample is then crushed in a crusher to obtain a granular or / and powdered polyglycolic acid sample.

[0061] Because polyglycolic acid, produced by the polymerization of glycolide (GL), has a simple, regular linear molecular structure, high crystallinity, and a large molecular weight, it cannot be dissolved by common solvents. Its internal structure must be altered under low-temperature liquid nitrogen conditions to facilitate dissolution. Therefore, the present invention provides a method for determining residual monomers in polyglycolic acid. This method pre-treats the polyglycolic acid sample by low-temperature embrittlement and fragmentation. This increases the contact area between the sample and the organic solvent, accelerates dissolution, shortens analysis time, and thus improves measurement efficiency.

[0062] Among them, the crushing time of the embrittled polyglycolic acid sample in the crusher is ≤1min.

[0063] Since glycolide monomer easily absorbs moisture in the air and undergoes hydrolysis, and temperature also promotes hydrolysis, the crushing time must be strictly controlled within 1 minute during the crushing process to avoid overheating of the crusher and affecting the sample composition.

[0064] Step 2) The pretreated polyglycolic acid sample is dissolved in hexafluoroisopropanol reagent to obtain a dissolved sample.

[0065] The step of dissolving the pretreated polyglycolic acid sample in a hexafluoroisopropanol reagent to dissolve the sample comprises:

[0066] First, take a pretreated polyglycolic acid sample with a mass of m1 and put it into the sample dissolution bottle.

[0067] Then add hexafluoroisopropanol reagent with a volume of V1 into the sample dissolution bottle.

[0068] Finally, the sample dissolving bottle is placed on a polymer dissolver to dissolve the pretreated polyglycolic acid sample to obtain a dissolved sample.

[0069] Since the chemical properties of the polyglycolic acid sample are relatively stable, this application uses hexafluoroisopropanol reagent as a dissolving reagent, which can completely dissolve the residual glycolide monomer in the polyglycolic acid sample and ensure the representativeness and integrity of the polyglycolic acid sample.

[0070] The dissolving temperature of the polymer dissolver is set to 25-59° C., and the stirring speed of the polymer dissolver is set to 50-600 rpm.

[0071] Since the boiling point of hexafluoroisopropanol is 59°C, the heating temperature should be below the boiling point. Therefore, controlling the dissolution temperature between 25-59°C can prevent the loss of organic solvents by volatilization. During the stirring process, the speed should not be too high. Controlling the stirring speed of the polymer dissolver between 50-600 rpm can avoid the formation of stirring vortexes and generate a large amount of bubbles and splashing.

[0072] The present invention provides a method for determining residual polyglycolic acid monomers. Hexafluoroisopropanol is used as a dissolving reagent and dissolved at a certain temperature and stirring speed. This method can completely dissolve the residual glycolide monomer in the polyglycolic acid sample, thereby ensuring the accuracy of the determination of residual polyglycolic acid monomers and also ensuring the representativeness and integrity of the determination of the polyglycolic acid sample.

[0073] Step 3) preparing an internal standard with a mass concentration of 0.5-5% using 4-chlorobenzophenone reagent and acetone reagent.

[0074] The step of preparing an internal standard with a mass concentration of 0.5-5% using a 4-chlorobenzophenone reagent and an acetone reagent comprises:

[0075] Take 4-chlorobenzophenone reagent m2 and acetone reagent m3 respectively in a mass ratio of 1:19-1:199.

[0076] Add the 4-chlorobenzophenone reagent m2 and the acetone reagent m3 into a screw-capped sample bottle and mix them evenly to obtain an internal standard with a mass concentration of 0.5-5%.

[0077] As a specific embodiment of the present invention, when the internal standard substance is prepared using the 4-chlorobenzophenone reagent and the acetone reagent, it is best to prepare the internal standard substance with a mass concentration of 1%.

[0078] As a specific embodiment of the present invention, when preparing an internal standard with a mass concentration of 1%, first take 4-chlorobenzophenone reagent m2 and acetone reagent m3 at a mass ratio of 1:99, and then add 4-chlorobenzophenone reagent m2 and acetone reagent m3 to a screw-capped sample bottle and mix evenly to obtain an internal standard with a mass concentration of 1%.

[0079] The internal standard prepared by the method of the present invention has high purity, will not introduce the substance to be tested, will not react with the substance to be tested, and will not interfere with the detection of the substance to be tested.

[0080] Step 4) The internal standard is mixed with the dissolved sample, precipitated and filtered to obtain a sample to be analyzed.

[0081] The steps of mixing the internal standard with the dissolved sample, precipitating and filtering to obtain the sample to be analyzed include:

[0082] First, take an internal standard substance of mass m4 and put it into the sample dissolution bottle.

[0083] Then add acetone reagent with a volume of V2 to the sample dissolution bottle and mix until the mixture becomes white and turbid.

[0084] Finally, after the precipitation is complete, the mixed solution is filtered with a syringe filter to obtain the sample to be analyzed.

[0085] Because hexafluoroisopropanol is a highly polar, fluorinated, protic solvent with strong hydrogen bond donor ability, it can effectively disrupt the hydrogen bonds and van der Waals forces between PGA molecular chains, causing it to dissolve. Acetone, on the other hand, is a moderately polar solvent. While it can dissolve some polymers, it has a weaker solubility for polyglycolic acid, especially high-molecular-weight polyglycolic acid.

[0086] Adding acetone reduces the polarity of the mixed solvent, resulting in a decrease in the solubility of polyglycolic acid and the aggregation and precipitation of molecular chains. Polyglycolic acid dissolves in organic reagents, and large amounts of soluble polyglycolic acid can interfere with the determination of glycolide monomer. The reagent is used to completely precipitate and filter the dissolved polyglycolic acid, ensuring the homogeneity of the sample components.

[0087] Step 5) Preset a standard solution in the gas chromatograph to establish an internal standard curve.

[0088] As a specific embodiment of the present invention, the prepared standard solution includes:

[0089] Glycolide, mass 0.0012g;

[0090] Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g);

[0091] Weigh 0.1004 g of the internal standard with a concentration of 1.0052%;

[0092] Acetone body, volume 5ml;

[0093] Hexafluoroisopropanol, volume 10 ml;

[0094] The mass of 4-chlorobenzophenone in the standard solution is 0.0010.

[0095] As another specific embodiment of the present invention, the prepared standard solution comprises:

[0096] glycolide, mass 0.0024 g;

[0097] Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g);

[0098] Weigh 0.1085 g of the internal standard with a concentration of 1.0052%;

[0099] Acetone body, volume 5ml;

[0100] Hexafluoroisopropanol, volume 10 ml;

[0101] The mass of 4-chlorobenzophenone in the standard solution is 0.0011.

[0102] As another specific embodiment of the present invention, the prepared standard solution comprises:

[0103] glycolide, mass 0.0062g;

[0104] Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g);

[0105] Weigh 0.1105 g of the internal standard with a concentration of 1.0052%;

[0106] Acetone body, volume 5ml;

[0107] Hexafluoroisopropanol, volume 10 ml;

[0108] The mass of 4-chlorobenzophenone in the standard solution is 0.0011.

[0109] The above three standard solutions are loaded into the gas chromatograph respectively, and internal standard methods for analyzing glycolide can be established respectively to perform quantitative analysis.

[0110] Step 6) The sample to be analyzed is placed in a sample injection bottle, and the sample to be analyzed is chromatographed and processed using a gas chromatograph internal standard method to obtain a chromatogram, residual monomer data, average relative error, and relative standard deviation. The residual monomer data is the weight percentage of the residual glycolide monomer in the analyzed sample.

[0111] The present invention provides a method for determining the residual polyglycolic acid, wherein the chromatogram of the residual polyglycolic acid sample is as follows: Figure 2 shown. Figure 2 It can reflect the chromatographic peaks of each component in the sample analysis process of the gas chromatography internal standard method.

[0112] The present invention provides a method for determining residual monomers in polyglycolic acid, which can accurately determine the content of residual glycolide monomer in a polyglycolic acid sample, thereby enabling accurate analysis of the residual monomers in the polyglycolic acid sample, ensuring the smooth operation of a production device, providing a reference basis for optimizing and adjusting process parameters, and efficiently assisting in process monitoring of polymerization reactions. This plays a vital role in quality judgment of end products and comparative procurement by downstream manufacturers, and is also directly related to the market prospects and market share of subsequent promotion of polyglycolic acid products, playing a decisive role and providing guiding significance.

[0113] Furthermore, the present invention provides a method for determining polyglycolic acid residues, which first pre-treats the polyglycolic acid sample by low-temperature embrittlement and crushing, thereby increasing the contact area between the sample and the organic solvent, accelerating its dissolution, shortening the analysis time, and improving the determination efficiency.

[0114] At the same time, the present invention provides a method for determining the residual monomers of polyglycolic acid, which uses hexafluoroisopropanol as a dissolving reagent, and can completely dissolve the residual glycolide monomer in the polyglycolic acid sample, thereby ensuring the accuracy of the determination of the residual monomers of polyglycolic acid, and also ensuring the representativeness and integrity of the determination of the polyglycolic acid sample.

[0115] The following examples illustrate a method for determining the residual content of polyglycolic acid provided by the present invention. The materials and instruments required for the present invention are as follows:

[0116] Gas chromatograph (with FID detector, DB-624 chromatographic column or equivalent), analytical balance (accuracy 0.0001g), polymer dissolver, crusher, 75ml sample bottle, 25ml graduated cylinder, 0.22um needle filter, 5ml disposable syringe, weighing paper, stainless steel sample cup, anti-freeze gloves, 1.5ml chromatographic injection bottle, 20ml screw-capped sample bottle, liquid nitrogen, acetone (GR), 4-chlorobenzophenone (>98%), hexafluoroisopropanol (>98%), glycolide (>98%).

[0117] Example 1

[0118] A method for determining the content of residual glycolide monomer in a polyglycolic acid sample comprises the following steps:

[0119] S101 Sample Pretreatment: First, place the polyglycolic acid sample in a stainless steel sample cup. Measure a certain volume of liquid nitrogen to completely submerge the sample to perform low-temperature embrittlement. The embrittled sample is then placed in a crusher and rapidly crushed within 1 minute to obtain a granular polyglycolic acid sample, a powdered polyglycolic acid sample, or a mixture of granules and powder.

[0120] S102 Sample dissolution: First, weigh 0.1025 g of polyglycolic acid sample into a 75 ml sample dissolution bottle; then use a measuring cylinder to transfer 10 mL of hexafluoroisopropanol reagent and add it to the sample dissolution bottle; set the temperature T1 of the polymer dissolver to 25°C and the stirring speed r1 to 600 rpm; after the temperature of the polymer dissolver stabilizes, place the sample dissolution bottle on the polymer dissolver and dissolve the sample to obtain a dissolved sample.

[0121] S103 Adding internal standard: First, weigh m2 of 4-chlorobenzophenone reagent and m3 of acetone reagent in a mass ratio of 1:99. Then, add the weighed 4-chlorobenzophenone reagent and acetone reagent to a 20 ml screw-cap sample bottle, mix well, and obtain a 1.0% internal standard.

[0122] S104 Interference Separation: Weigh 1.0% of the internal standard (m4) by mass and place it into the sample vial containing the dissolved sample. Then, add a volume of acetone (V2) to the sample vial using a graduated cylinder and mix. A white, turbid precipitate will appear after mixing. This white precipitate is the polyglycolic acid precipitated from the polyglycolic acid sample. After precipitation is complete, filter the sample using a 5ml disposable syringe and a 0.22µm syringe filter to obtain the sample to be analyzed.

[0123] S105 Establish internal standard curve: preset standard solution in gas chromatograph, establish internal standard curve, the standard solution prepared in the embodiment of the present invention is shown in Table 1. The standard solution is loaded into the gas chromatograph, establish internal standard method for analyzing glycolide and perform quantitative analysis.

[0124] Table 1 Internal standard method standard solution established

[0125] Standard solution 1 2 3 Glycolide mass / g 0.0012 0.0024 0.0062 4-Chlorobenzophenone mass / g 0.1007 0.1007 0.1007 Acetone mass / g 9.9178 9.9178 9.9178 Concentration of prepared internal standard / % 1.0052 1.0052 1.0052 Weigh 1% internal standard mass / g 0.1004 0.1085 0.1105 Mass of 4-chlorobenzophenone in standard solution / g 0.0010 0.0011 0.0011 Acetone volume / ml (for precipitation of polyglycolic acid) 5 5 5 Hexafluoroisopropanol volume / ml 10 10 10

[0126] At the same time, the gas chromatograph parameter conditions are set, and the gas chromatograph parameter conditions are shown in Table 2.

[0127] Table 2 Gas chromatograph parameter conditions

[0128]

[0129]

[0130] S106 Chromatographic Analysis: Add the sample to be analyzed to a 1.5 ml injection vial and perform chromatographic analysis and data processing using the internal standard method on the gas chromatograph to obtain a chromatogram, residual monomer data, average relative error, and relative standard deviation. The residual monomer data represents the weight percentage of glycolide monomer remaining in the sample.

[0131] The calculation formula involved in the data processing process is as follows:

[0132]

[0133] Among them A s and A r are the peak areas of the internal standard and control components, m s and m r The amounts of internal standard and control components added are respectively expressed in grams (g).

[0134]

[0135] Among them A s and A i are the peak areas of the internal standard and the component to be measured, m sTo add the amount of internal standard, calculate the component to be tested m by the formula i The amount by mass in grams (g).

[0136]

[0137] Wherein m is the weight of the polyglycolic acid (PGA) sample, in grams (g).

[0138] Apply formula (1)-(3) to process the data, A in (1) S and m s are the peak area and mass of the known internal standard 4-benzophenone, A r and m r The peak area and mass of glycolide monomer are known, and the coefficient f is obtained by calculation. S and m s is the peak area and mass of the known internal standard 4-benzophenone in the sample, A i and m i is the known peak area and unknown mass of glycolide monomer in the sample, f is obtained in formula (1), and formula (2) mainly requires the mass m of glycolide monomer in the sample i Formula (3) is used to obtain the ratio of glycolide monomer in the sample to the sample mass m to obtain the residual monomer data as shown in Table 2.

[0139] S106 adds the sample to be analyzed to a 1.5 ml injection bottle, and performs chromatographic analysis on the sample to be analyzed using the internal standard method in the gas chromatograph to obtain a chromatogram. Formulas (1)-(3) are used to perform data processing to obtain residual single data, and the standard solution is loaded into the gas chromatograph, and an internal standard method for analyzing glycolide is established to perform quantitative analysis. Finally, the average relative error and relative standard deviation are calculated. The relevant data of the embodiment of the present invention are shown in Table 3.

[0140] Table 3 Polyglycolic acid sample residual data table

[0141]

[0142] S107 spike recovery experiment

[0143] A certain amount of glycolide, the component to be tested, was added to the polyglycolic acid sample and the above method was followed to calculate the spiked recovery rate. The recovery rates of the examples of the present invention are shown in Table 4.

[0144] Table 4 Recovery data of spiked polyglycolic acid samples

[0145]

[0146]

[0147] Example 2

[0148] This example provides a method for determining residual monomers in polyglycolic acid. This method differs from Example 1 in that the mass of the pretreated polyglycolic acid sample, the mass of added glycolide, the mass of the 1% internal standard, the mass of 4-chlorobenzophenone in the sample, and the instrument readings before and after spike addition are slightly different. The relevant data for this example are shown in Tables 3 and 4. Furthermore, in this example, the polymer dissolver temperature T1 was set to 58.9°C and the stirring speed r1 was set to 50 rpm. The residual monomers, average relative error, and relative standard deviation measured in this example are shown in Table 3. The recovery rates in the spike recovery experiments in this example are shown in Table 4.

[0149] Example 3

[0150] This example provides a method for determining residual monomers in polyglycolic acid. This method differs from Example 1 in that the mass of the pretreated polyglycolic acid sample, the mass of added glycolide, the mass of the 1% internal standard, the mass of 4-chlorobenzophenone in the sample, and the instrument readings before and after spike addition are slightly different. The relevant data for this example are shown in Tables 3 and 4. Furthermore, in this example, the polymer dissolver temperature T1 was set to 42°C and the stirring speed r1 was set to 275 rpm. The residual monomers, average relative error, and relative standard deviation measured in this example are shown in Table 3. The recovery rates in the spike recovery experiments in this example are shown in Table 4.

[0151] Example 4

[0152] This example provides a method for determining residual monomers in polyglycolic acid. This method differs from Example 1 in that the mass of the pretreated polyglycolic acid sample, the mass of added glycolide, the mass of the 1% internal standard, the mass of 4-chlorobenzophenone in the sample, and the instrument readings before and after spike addition are slightly different. The relevant data for this example are shown in Tables 3 and 4. Furthermore, in this example, the polymer dissolver temperature T1 was set at 50°C and the stirring speed r1 was set at 400 rpm. The residual monomers, average relative error, and relative standard deviation measured in this example are shown in Table 3. The recovery rates in the spike recovery experiments in this example are shown in Table 4.

[0153] Example 5

[0154] This example provides a method for determining residual monomers in polyglycolic acid. This method differs from Example 1 in that the mass of the pretreated polyglycolic acid sample, the mass of added glycolide, the mass of the 1% internal standard, the mass of 4-chlorobenzophenone in the sample, and the instrument readings before and after spike addition are slightly different. The relevant data for this example are shown in Tables 3 and 4. Furthermore, in this example, the polymer dissolver temperature T1 was set at 59°C and the stirring speed r1 was set at 50 rpm. The residual monomers, average relative error, and relative standard deviation measured in this example are shown in Table 3. The recovery rates in the spike recovery experiments in this example are shown in Table 4.

[0155] As shown in Tables 3 and 4, the average relative error, relative standard deviation, and spike recovery data for the polyglycolic acid samples of various embodiments of the present invention further demonstrate that the polyglycolic acid residual monomer determination method provided by the present invention has relatively high precision and accuracy, meeting the specific RSD requirements of national standards such as the Chinese Pharmacopoeia, GB5009 series, HJ series, and GB / T223 series, and meeting analytical requirements. The resulting residual monomer analysis data is accurate and reliable, with high precision and accuracy. Therefore, the determination method provided by the embodiments of the present invention can be used as an analytical method for the residual monoglycolide monomer content of polyglycolic acid.

[0156] The method for determining the residual polyglycolic acid provided in the embodiment of the present invention has the following advantages:

[0157] 1. Use liquid nitrogen to embrittle the sample at low temperature, change the internal molecular structure of the substance, and enable the sample to be effectively dissolved in the reagent solution.

[0158] 2. Crushing samples with larger particle sizes and reducing the particle size will facilitate sample dissolution and reduce analysis time.

[0159] 3. The results of the internal standard method are more accurate and, to a certain extent, eliminate the errors caused by changes in operating conditions.

[0160] 4. As long as the ratio of the amount of the component to be measured to the amount of the internal standard in the mixed solution is constant, changes in the sample volume will not affect the quantitative results.

[0161] Therefore, the method for determining polyglycolic acid residues provided in this embodiment can effectively fill the gap in residue analysis projects in the industry and field. The method is simple to operate, has low energy consumption, fast analysis, and can provide analysis data in a timely and accurate manner.

[0162] Finally, it should be noted that the above specific implementation methods are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to examples, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A method for determining the content of residual glycolide monomer in a polyglycolic acid sample, characterized in that: The steps include: Pretreatment of polyglycolic acid samples for low-temperature embrittlement and crushing; The pretreated polyglycolic acid sample is dissolved in hexafluoroisopropanol reagent to obtain a dissolved sample; An internal standard with a mass concentration of 0.5-5% is prepared using 4-chlorobenzophenone reagent and acetone reagent; The internal standard substance is mixed with the dissolved sample, and then precipitated and filtered to obtain a sample to be analyzed; Preset the standard solution in the gas chromatograph to establish the internal standard curve; The sample to be analyzed is placed in an injection bottle, and the sample to be analyzed is chromatographically analyzed and the data is processed by the internal standard method of gas chromatography to obtain the chromatogram, residual data, average relative error and relative standard deviation.

2. The method for determining the residual polyglycolic acid according to claim 1, wherein: The polyglycolic acid sample pretreatment step comprises: Place the polyglycolic acid sample in a sample cup and add liquid nitrogen until the sample is completely covered to embrittle the sample at low temperature; The embrittled polyglycolic acid sample is crushed in a crusher to obtain a granular or / and powdered polyglycolic acid sample.

3. The method for determining the residual polyglycolic acid according to claim 2, wherein: The step of dissolving the pretreated polyglycolic acid sample in a hexafluoroisopropanol reagent to dissolve the sample comprises: Take a pretreated polyglycolic acid sample with a mass of m1 and put it into a sample dissolution bottle; Add hexafluoroisopropanol reagent with a volume of V1 into the sample dissolution bottle; The sample dissolving bottle is placed on a polymer dissolver to dissolve the pretreated polyglycolic acid sample to obtain a dissolved sample.

4. The method for determining the residual polyglycolic acid according to claim 3, wherein: The dissolving temperature of the polymer dissolver is set to 25-59° C., and the stirring speed of the polymer dissolver is set to 50-600 rpm.

5. The method for determining the residual polyglycolic acid according to claim 3, wherein: The step of preparing an internal standard with a mass concentration of 0.5-5% by using a 4-chlorobenzophenone reagent and an acetone reagent comprises: 4-Chlorobenzophenone reagent m2 and acetone reagent m3 are prepared respectively in a mass ratio of 1:19-1:199; Add the 4-chlorobenzophenone reagent m2 and the acetone reagent m3 into a screw-capped sample bottle and mix them evenly to obtain an internal standard with a mass concentration of 0.5-5%.

6. The method for determining the residual polyglycolic acid according to claim 5, wherein: The steps of mixing the internal standard with the dissolved sample, precipitating and filtering to obtain the sample to be analyzed include: Take the internal standard substance of mass m4 and put it into the sample dissolution bottle; Add volume V2 of acetone reagent to the sample dissolution bottle and mix until the mixture becomes white and turbid; After the precipitation is complete, the mixed solution is filtered with a syringe filter to obtain the sample to be analyzed.

7. The method for determining the residual polyglycolic acid according to claim 1, wherein: The standard solution comprises: Glycolide, mass 0.0012g; Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g); Weigh 0.1004 g of the internal standard with a concentration of 1.0052%; Acetone, volume 5ml; Hexafluoroisopropanol, volume 10 ml; The mass of 4-chlorobenzophenone in the standard solution is 0.0010.

8. The method for determining the residual polyglycolic acid according to claim 1, wherein: The standard solution comprises: Glycolide, mass 0.0024g; Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g); Weigh 0.1085 g of the internal standard with a concentration of 1.0052%; Acetone, volume 5ml; Hexafluoroisopropanol, volume 10 ml; The mass of 4-chlorobenzophenone in the standard solution is 0.0011.

9. The method for determining the residual polyglycolic acid according to claim 1, wherein: The standard solution comprises: glycolide, mass 0.0062g; Internal standard, concentration 1.0052%: 4-chlorobenzophenone (mass 0.1007 g), acetone (mass 9.9178 g); Weigh 0.1105 g of the internal standard with a concentration of 1.0052%; Acetone, volume 5ml; Hexafluoroisopropanol, volume 10 ml; The mass of 4-chlorobenzophenone in the standard solution is 0.0011.

10. The method for determining the residual polyglycolic acid according to claim 2, wherein: The crushing time is ≤1 min.

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