Method for simultaneously detecting residual quantity of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical material

Abstract

The invention discloses a method for simultaneously detecting the residual quantity of 1-vinyl-2-pyrrolidone and a photoinitiator 2959 in a medical material. According to the method, the medical material is subjected to extraction treatment by adding methanol, then an extraction solution is detected by using a gas chromatograph-mass spectrometer, and according to a linear regression equation and logarithm values of peak areas represented by 1-vinyl-2-pyrrolidone and a photoinitiator 2959 in a chromatogram of the extraction solution, the content of the medical material is determined according to the logarithm values of peak areas represented by the 1-vinyl-2-pyrrolidone and the photoinitiator 2959. And calculating the residual quantity of the 1-vinyl-2-pyrrolidone and the photoinitiator 2959 in the medical material. The detection method disclosed by the invention is good in repeatability, high in sensitivity, simple and rapid, accurate in result and suitable for detecting the residual quantity of the 1-vinyl-2-pyrrolidone and the photoinitiator 2959 in a medical material (especially a medical instrument).

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medical material detection, and particularly relates to a method for simultaneously detecting residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials. BACKGROUND

[0002] 1-vinyl-2-pyrrolidone (NVP, CAS No 88-12-0) is an important nitrogen-containing heterocyclic compound with vinyl and pyrrolidone structures. Due to its high reactivity and good solubility, NVP is widely used in polymer synthesis, medicine, cosmetics, industrial aids and other fields. Although NVP is widely used in the pharmaceutical, cosmetic and food industries, NVP monomer itself has certain toxicity. Therefore, it is necessary to monitor and control the residual amount of 1-vinyl-2-pyrrolidone.

[0003] 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (photoinitiator 2959, CAS No 106797-53-9) is a highly efficient photoinitiator, which is widely used in light-cured materials in medical devices, and the photoinitiator is also used in microfluidic devices and wound dressings to improve production efficiency and product performance. For example, the photoinitiator 2959 is used for the preparation of a biomimetic dermis layer in the patent application "Biomimetic skin model for drug transdermal release research" CN202510208992.5. The photoinitiator 2959 has excellent photosensitivity, stability, low volatility, low odor, high reactivity and good compatibility with various resins. It belongs to low toxicity to moderate toxicity, has no significant genetic toxicity or carcinogenicity, but its toxicological properties are of concern because it may directly or indirectly contact the human body (such as implant material residues).

[0004] At present, there is no relevant national standard or industry standard detection method for 1-vinyl-2-pyrrolidone and photoinitiator 2959, and the commonly used detection methods are mostly liquid chromatography. SUMMARY

[0005] The purpose of the present application is to provide a simple and efficient method for simultaneously detecting the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials (especially medical devices).

[0006] The technical solution adopted by the present application is as follows: a method for simultaneously detecting residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials, the method comprising the following steps:

[0007] S1. Sample pretreatment: the sample is placed in a polytetrafluoroethylene bottle, a methanol extraction solution is added, and after sealing, the sample is oscillated and extracted in a constant temperature oscillation incubator to obtain a sample extraction solution; similarly, a methanol extraction solution without the sample is used as a sample blank extraction solution;

[0008] The sample is extracted with methanol, the extraction solution does not need pretreatment and can be directly tested on the machine; the solvent delay is 5.5 min, which can prolong the service life of the filament; and the single needle operation time is only 13 min.

[0009] S2. Solution preparation: a mixed standard working solution of 1-vinyl-2-pyrrolidone and photoinitiator 2959 is prepared with a methanol solution, and a repeatability solution, a detection limit solution, a limit of quantification solution, a mixed standard curve solution and an accuracy solution are prepared; the repeatability solution is a 0.60 μg / mL mixed standard working solution; the detection limit solution is a 0.01 μg / mL mixed standard working solution, the limit of quantification solution is a 0.05 μg / mL mixed standard working solution, the concentration range of the mixed standard curve solution is set to 0.05 μg / mL-1.0 μg / mL, and the accuracy solution is a mixed standard working solution with low, medium and high concentrations;

[0010] S3. Qualitative analysis: the series of mixed standard working solutions are analyzed by using a gas chromatograph-mass spectrometer to obtain chromatograms and mass spectra of 1-vinyl-2-pyrrolidone and photoinitiator 2959, and the peak time, qualitative ions and quantitative ions are analyzed by using a NEST database;

[0011] S4. Establishment of a test method: a quantitative method is established according to the peak time, qualitative ions and quantitative ions of 1-vinyl-2-pyrrolidone and photoinitiator 2959 standard substances, and the repeatability solution, the detection limit solution, the limit of quantification solution, the mixed standard curve solution and the accuracy solution are analyzed by using a gas chromatograph-mass spectrometer;

[0012] S5. Method verification data analysis: the repeatability solution is injected for 6 times to obtain a repeatability result; the detection limit solution is repeatedly injected for 3 times for analysis to calculate a signal-to-noise ratio; the limit of quantification solution is repeatedly injected for 3 times for analysis to calculate a signal-to-noise ratio; the mixed standard curve solution is subjected to linear regression analysis to obtain a linear regression equation and establish a standard curve; and the mixed standard working solution with low, medium and high concentrations is analyzed to obtain an accuracy result;

[0013] S6. Quantitative analysis: the sample solution is determined by using a gas chromatograph-mass spectrometer to quantitatively analyze the residual amount of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in the sample solution.

[0014] The method has good repeatability, high sensitivity, high efficiency, fast speed, accurate results and convenient operation.

[0015] 1-Vinyl-2-pyrrolidone and photoinitiator 2959 are volatile and readily soluble in organic solvents such as methanol. Therefore, this invention utilizes this property to describe a simple and efficient gas chromatography-mass spectrometry method for the detection of 1-vinyl-2-pyrrolidone and photoinitiator 2959.

[0016] In step S1, the sample is placed in a polytetrafluoroethylene bottle, the extraction solution is methanol solvent (99.9%), and after the bottle cap is sealed, it is extracted in a constant temperature shaking incubator at 37°C at a rate of 60 r / min for 24 h.

[0017] In step S2, the concentration of the mixed standard working solution is 10 μg / mL; the concentration of the repeatability solution is 0.60 μg / mL (n=6); the detection limit solution is 0.01 μg / mL of the mixed standard working solution; the quantitation limit solution is 0.05 μg / mL of the mixed standard working solution; the concentration range of the mixed standard curve solution is set to 0.05 μg / mL, 0.10 μg / mL, 0.20 μg / mL, 0.40 μg / mL, 0.6 μg / mL, and 1.0 μg / mL; the accuracy solution is prepared by adding standard solutions to the sample blank solution to prepare mixed standard working solutions with concentrations of 0.15 μg / mL, 0.40 μg / mL, and 0.60 μg / mL.

[0018] In step S3, the mixed standard working solution is analyzed by gas chromatography-mass spectrometry to obtain chromatograms and mass spectra of 1-vinyl-2-pyrrolidone and photoinitiator 2959. Analysis using the NEST database determines that the peak time of the 1-vinyl-2-pyrrolidone standard is 6.78 min, the qualitative ion is 111 m / z, and the quantitative ions are 56 m / z and 68 m / z. The peak time of the photoinitiator 2959 standard is determined to be 12.34 min, the qualitative ion is 121 m / z, and the quantitative ions are 59 m / z and 165 m / z.

[0019] In step S4, the chromatographic conditions for the gas chromatography-mass spectrometry (GC-MS) are as follows:

[0020] Flow rate: 1 mL / min; Column: HP-5MS UI, 30 m × 250 μm × 0.25 μm; Temperature program: Initial temperature 60 °C, hold for 3 min, increase to 220 °C at a rate of 20 °C / min, hold for 2 min; Injector temperature: 280 °C; Injection volume: 1 μL; Split mode: Splitless; Carrier gas: He; Mass transfer line temperature: 300 °C.

[0021] In step S4, the mass spectrometry conditions for the gas chromatography-mass spectrometry (GC-MS) are as follows:

[0022] Ion source: EI; Ion source temperature: 230 °C; Quadrupole temperature: 150 °C; Solvent delay time: 5.5 min; Scan mode and range: SCAN / SIM; Range: 29-550 m / z.

[0023] In the step S5, the repeatability solution is analyzed to obtain a repeatability result; the detection limit solution is repeatedly injected for 3 times and analyzed to calculate a signal-to-noise ratio; the quantification limit solution is repeatedly injected for 3 times and analyzed to calculate a signal-to-noise ratio; the series of mixed standard working solutions are analyzed by linear regression to obtain a linear regression equation and establish a standard curve; the mixed standard working solutions with concentrations of 0.15 μg / mL, 0.40 μg / mL and 0.60 μg / mL are analyzed to obtain an accuracy result.

[0024] In summary, by adopting the technical solutions described above, the present application has the following beneficial effects:

[0025] 1. In the present application, the standard solutions of 1-vinyl-2-pyrrolidone and photoinitiator 2959 are determined by using a gas chromatograph-mass spectrometer to obtain corresponding chromatograms and mass spectra, qualitative analysis is performed by using a NIST database, the peak time, qualitative ions and quantitative ions of the 1-vinyl-2-pyrrolidone and photoinitiator 2959 standard substances are determined, and a quantitative detection method can be quickly established.

[0026] 2. In the present application, a strict experimental design and verification process are adopted to ensure the accuracy and reliability of the detection of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical material (especially medical devices) leaching solutions.

[0027] 3. In the present application, the detection method established can simultaneously detect the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials, the sample is extracted with methanol, the extraction solution does not need to be pretreated and can be directly tested on the machine, the solvent delay time is 5.5 min, the service life of the filament can be prolonged, the single needle operation time is only 13 min, and the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials can be simply, quickly and simultaneously detected. The method has good repeatability, high sensitivity, high efficiency, fast speed, accurate results and convenient operation. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 The figure is a specific gas chromatogram provided in the embodiments of the present application.

[0029] Figure 2 The figure is a mass spectrum of 1-vinyl-2-pyrrolidone in the embodiments of the present application.

[0030] Figure 3 The figure is a mass spectrum of photoinitiator 2959 in the embodiments of the present application.

[0031] Figure 4 The standard curve diagram of 1-vinyl-2-pyrrolidinone in the embodiment of the present application.

[0032] Figure 5 The standard curve solution gas chromatogram of 1-vinyl-2-pyrrolidinone in the embodiment of the present application.

[0033] Figure 6 The standard curve diagram of photoinitiator 2959 in the embodiment of the present application.

[0034] Figure 7 The standard curve solution gas chromatogram of photoinitiator 2959 in the embodiment of the present application.

[0035] Figure 8 The sample solution and sample blank solution gas chromatogram in the embodiment of the present application. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical scheme and advantages of the present application more clear, the present application is further described in detail below in combination with the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and do not limit the present application.

[0037] Embodiment:

[0038] In this embodiment, a short-term contact medical device disposable scale guide wire is selected to detect the residual amount of 1-vinyl-2-pyrrolidinone and photoinitiator 2959 in the disposable scale guide wire extract, and the steps are as follows:

[0039] 1. Sample pretreatment: the sample is placed in a polytetrafluoroethylene bottle, 17 mL of methanol solution is added, the bottle is sealed and incubated in a 37°C constant temperature shaking incubator at a shaking speed of 60 r / min for 24 h to obtain the sample extract, and two samples are prepared in parallel, and the methanol extract solution without sample is used as a blank extract solution.

[0040] 2. Solution preparation: 10 μg / mL mixed standard working solution, 0.60 μg / mL repeatability solution (n=6), 0.05 μg / mL, 0.10 μg / mL, 0.20 μg / mL, 0.40 μg / mL, 0.60 μg / mL, 1.0 μg / mL mixed standard curve solution, 0.01 μg / mL detection limit solution, 0.05 μg / mL limit of quantification solution, 0.15 μg / mL, 0.40 μg / mL, 0.60 μg / mL accuracy solution are prepared with methanol solution.

[0041] Table 1 Solution preparation information

[0042]

[0043] 3. Qualitative analysis: 10 pg / mL mixed standard working solution was analyzed by gas chromatography-mass spectrometry to obtain the chromatogram and mass spectrum of 1-vinyl-2-pyrrolidone and photoinitiator 2959. Through NEST database analysis, it was determined that:

[0044] The peak time of 1-vinyl-2-pyrrolidone standard substance was 6.78 min, the qualitative ion was 111 m / z, and the quantitative ion was 56 m / z, 68 m / z; the peak time of photoinitiator 2959 standard substance was 12.34 min, the qualitative ion was 121 m / z, and the quantitative ion was 59 m / z, 165 m / z. The chromatogram results are shown in Figure 1 , the mass spectrum results are shown in Figure 2 、 Figure 3 .

[0045] 4. Establishment of test method: According to the peak time, qualitative ion and quantitative ion of 1-vinyl-2-pyrrolidone and photoinitiator 2959 standard substance, a quantitative method was established, and the repeatability solution, detection limit solution, quantification limit solution, mixed standard curve solution, accuracy solution were analyzed by gas chromatography-mass spectrometry. The test method is shown in Table 2.

[0046] Table 2 GC-MS instrument conditions

[0047]

[0048]

[0049] 5. Method validation data analysis: 6 injections of repeatability solution were obtained, the repeatability results were obtained; 3 injections of detection limit solution were analyzed, the signal-to-noise ratio was calculated; 3 injections of quantification limit solution were analyzed, the signal-to-noise ratio was calculated; the mixed standard curve solution was linearly regressed to obtain the linear regression equation and establish the standard curve; the mixed standard working solution of low, medium and high concentration was analyzed to obtain the accuracy result. The method validation data analysis results are shown in Tables 3-6, the standard curve diagram is shown in Figure 4 、 Figure 6 , the chromatogram of the standard curve solution is shown in Figure 5 、 Figure 7 . According to the results of method validation data, it is proved that the method has good repeatability, linearity and accuracy, and the specific lower detection limit.

[0050] Table 3 Repeatability results

[0051]

[0052] Table 4 Detection limit and quantification limit results

[0053]

[0054]

[0055] Table 5 linear results

[0056] Serial Number CAS Number Name Linear Equation Correlation Coefficient R 1 88-12-0 1 -Vinyl-2-pyrrolidinone y = 65484.341393 * x - 2187.731906 0.9993 2 106797-53-9 Photoinitiator 2959 y = 6460.401968 * x - 410.047645 0.9974

[0057] Table 6 accuracy results

[0058]

[0059] 6. Quantitative analysis: the sample solution is determined by using a gas chromatograph-mass spectrometer, so as to quantitatively analyze the residual amount of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in the sample solution; the detection results are shown in Table 7, and the chromatograms of the sample solution and the sample blank solution are shown in Figure 8 .

[0060] Table 7 detection results of the leaching solution

[0061]

[0062] It can be known from the above that the present application can detect the residual amount of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials (especially medical devices), and a strict experimental design and verification process are adopted to ensure the accuracy and reliability of the detection of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials. In the present application, the medical materials are subjected to leaching treatment by adding methanol, and then the leaching solution is detected by using a gas chromatograph-mass spectrometer, and according to the linear regression equation and the logarithmic value of the peak area of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in the chromatogram of the leaching solution, the residual amount of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in the medical materials is calculated. The detection method of the present application has good repeatability, high sensitivity, is simple, rapid and accurate, and is suitable for the detection of the residual amount of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials (especially medical devices).

[0063] It is to be noted that, in the present text, relational terms such as first and second and the like can be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises", "comprising", or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can also include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element proceeded by "comprises... a" does not, without more constraints, exclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0064] The above embodiments are only used to illustrate the technical solutions of the present application, rather than limit the present application; even though the present application has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacement for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for simultaneously detecting the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials, characterized in that: The method includes the following steps: S1. Sample pretreatment: Place the samples in polytetrafluoroethylene bottles, add methanol extraction solution, seal and then shake in a constant temperature shaking incubator to obtain sample extract; similarly, use the methanol extraction solution without sample as sample blank extract. S2. Solution Preparation: Prepare a mixed standard working solution, a repeatability solution, a limit of detection solution, a limit of quantitation solution, a mixed standard curve solution, and an accuracy solution using methanol solution; the repeatability solution is a 0.60 μg / mL mixed standard working solution; the limit of detection solution is a 0.01 μg / mL mixed standard working solution; the limit of quantitation solution is a 0.05 μg / mL mixed standard working solution; the concentration range of the mixed standard curve solution is set to 0.05 μg / mL to 1.0 μg / mL; and the accuracy solution is a mixed standard working solution with low, medium, and high concentrations. S3. Qualitative analysis: The series of mixed standard working solutions were analyzed using gas chromatography-mass spectrometry to obtain chromatograms and mass spectra of 1-vinyl-2-pyrrolidone and photoinitiator 2959. The peak times, qualitative ions and quantitative ions were analyzed using the NEST database. S4. Establish test method: Based on the peak time, qualitative ions and quantitative ions of 1-vinyl-2-pyrrolidone and photoinitiator 2959 standard material, establish a quantitative method, and use gas chromatography-mass spectrometry to analyze the repeatability solution, detection limit solution, quantitation limit solution, mixed standard curve solution and accuracy solution; S5. Method Validation Data Analysis: Six injections of the repeatability solution were performed to obtain repeatability results; three injections of the detection limit solution were performed for analysis, and the signal-to-noise ratio was calculated; three injections of the quantitation limit solution were performed for analysis, and the signal-to-noise ratio was calculated; linear regression analysis was performed on the mixed standard curve solution to obtain the linear regression equation and establish a standard curve; the mixed standard working solutions of low, medium, and high concentrations were analyzed to obtain accuracy results; S6. Quantitative analysis: The sample solution was analyzed by gas chromatography-mass spectrometry to quantitatively determine the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in the sample solution.

2. The method for simultaneously detecting the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials as described in claim 1, characterized in that: In step S1, the sample is placed in a polytetrafluoroethylene bottle, the extraction solution is methanol solvent (99.9%), and after the bottle cap is sealed, it is extracted in a constant temperature shaking incubator at 37°C at a rate of 60 r / min for 24 h.

3. The method for simultaneously detecting the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials as described in claim 1, characterized in that: In step S2, the concentration of the mixed standard working solution is 10 μg / mL; the concentration of the repeatability solution is 0.60 μg / mL (n=6); the detection limit solution is 0.01 μg / mL of the mixed standard working solution; the quantitation limit solution is 0.05 μg / mL of the mixed standard working solution; the concentration range of the mixed standard curve solution is set to 0.05 μg / mL, 0.10 μg / mL, 0.20 μg / mL, 0.40 μg / mL, 0.60 μg / mL, and 1.0 μg / mL; the accuracy solution is prepared by adding standard solutions to the sample blank solution to prepare mixed standard working solutions with concentrations of 0.15 μg / mL, 0.40 μg / mL, and 0.60 μg / mL.

4. The method for simultaneously detecting the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials as described in claim 1, characterized in that: In step S4, the chromatographic conditions for the gas chromatography-mass spectrometry (GC-MS) are as follows: Flow rate: 1 mL / min; Column: HP-5MS UI, 30 m × 250 μm × 0.25 μm; Temperature program: Initial temperature 60 °C, hold for 3 min, increase to 220 °C at a rate of 20 °C / min, hold for 2 min; Injector temperature: 280 °C; Injection volume: 1 μL; Split mode: Splitless; Carrier gas: He; Mass transfer line temperature: 300 °C.

5. The method for simultaneously detecting the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials as described in claim 1, characterized in that: In step S4, the mass spectrometry conditions for the gas chromatography-mass spectrometry (GC-MS) are as follows: Ion source: EI; Ion source temperature: 230℃; Quadrupole temperature: 150℃; Solvent delay time: 5.5 min; Scan mode and range: SCAN / SIM; Range: 29~550m / z.

6. The method for simultaneously detecting the residual amounts of 1-vinyl-2-pyrrolidone and photoinitiator 2959 in medical materials as described in claim 1, characterized in that: In step S5, the repeatability solution is analyzed to obtain repeatability results; the detection limit solution is analyzed after three repeated injections and the signal-to-noise ratio is calculated; the quantitation limit solution is analyzed after three repeated injections and the signal-to-noise ratio is calculated; the series of mixed standard curve solutions are subjected to linear regression analysis to obtain a linear regression equation and establish a standard curve; the accuracy solutions with concentrations of 0.15 μg / mL, 0.40 μg / mL, and 0.60 μg / mL are analyzed to obtain accuracy results.

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