Method for measuring extractable amount of organic silicon in contact lens

Abstract

The invention relates to the technical field of contact lens detection, in particular to a method for measuring the extractable amount of organic silicon in a contact lens, which comprises the following steps: S1, preparing a series of standard solutions; s2, establishing a standard curve, injecting the series of standard solutions prepared in the step S1 into a gas chromatograph for gas chromatographic determination, and establishing a linear regression equation, namely the standard curve; s3, taking a contact lens to-be-detected product, and preparing a test solution after extraction; and S4, injecting the test solution prepared in the step S3 into a gas chromatograph for gas chromatographic determination, recording to obtain a relative response value of the peak area of the organic silicon and the internal standard substance, substituting the relative response value into the linear regression equation, and calculating to obtain the concentration of the organic silicon in the contact lens, namely the extractable amount. The organic silicon is methacryloyloxypropyl tri (trimethylsiloxane) silane; the internal standard substance is n-octadecane; according to the method provided by the invention, the accurate detection of the extractable amount of the methacryloyloxypropyl tri (trimethylsilyl) silane in the contact lens is realized.

Description

Technical Field

[0001] The present invention relates to the technical field of contact lens detection, and specifically, to a method for determining the extractable amount of organosilicon in contact lenses. Background Art

[0002] Methacryloxypropyltris(trimethylsiloxy)silane is an important organosilicon, which is often added to contact lenses as a crosslinking agent. This organosilicon contains two functional groups, acryloxy group and trimethylsiloxy group. The former is easy to copolymerize with the acrylate matrix monomer in the contact lens, making the contact lens have good mechanical properties; the latter will form a large number of oxygen-permeable voids during polymerization, improving the oxygen permeability of the contact lens. At the same time, this organosilicon has good hydration and biocompatibility. Therefore, this organosilicon is usually added during the preparation of contact lenses, especially in the preparation of rigid gas-permeable contact lenses. Patent documents CN111062535A, CN106932920A and CN104877068A all use this organosilicon to prepare contact lenses.

[0003] However, the siloxy group in the organosilicon has strong fluidity and is easy to migrate to the surface of the contact lens, which will reduce the comfort of the user wearing the contact lens and may cause other adverse reactions such as eye redness and blurred vision (references include Li Fan. Preparation and Properties of Methacryloylethylsulfobetaine Modified Contact Lenses [D]. Changchun University of Technology, 2023; Cai Libin. Research on Organosilicon Modified Hydrogel Contact Lens Materials [D]. Northwestern Polytechnical University, 2006; Matsumoto Eiri; Nakata Atsuko. Ophthalmic Composition for Silicone Hydrogel Contact Lenses [P]. CN102470115A, 2023-05-23). In addition, the national standard GB / T11417.7-2012 "Ophthalmic Optics - Contact Lenses - Part 7: Test Methods for Physical and Chemical Properties" requires that the extractables in the lens be enriched by Soxhlet extraction and the content of the extractables in the lens be accurately determined by appropriate analytical methods. However, there is currently no detection method for the extractable amount of methacryloxypropyltris(trimethylsiloxy)silane in contact lenses, which will reduce the credibility of the chemical characterization evaluation of contact lenses and cause ophthalmic medical risks.

[0004] Therefore, it is necessary to establish a detection method that can accurately determine the extractable amount of methacryloxypropyltris(trimethylsiloxy)silane in contact lenses. Summary of the Invention

[0005] The purpose of the present invention is to overcome the above-mentioned deficiencies of the prior art and provide a method for detecting the extractable amount of methacryloxypropyltris(trimethylsiloxy)silane in contact lenses. This method is simple to operate, highly specific, and sensitive, and can fill the gaps in the existing domestic and foreign technologies.

[0006] To achieve the above technical effects, the present invention adopts the following technical solutions:

[0007] A method for determining the extractable amount of silicone in a contact lens, comprising the following steps:

[0008] S1. Preparation of a series of standard solutions

[0009] Take the internal standard substance and dissolve it in dichloromethane to obtain an internal standard solution. Take the standard substance of silicone and dissolve it in dichloromethane to obtain a standard stock solution. Take the internal standard solution and the standard stock solution to prepare a series of standard solutions with a concentration of 0.1 μg / mL - 1.6 μg / mL, wherein the internal standard concentration is 1 μg / mL;

[0010] S2. Establish a standard curve

[0011] Inject the series of standard solutions prepared in step S1 into a gas chromatograph for gas chromatographic determination. Respectively measure the relative response values of the peak areas of silicone and the internal standard substance in the series of standard solutions with different concentrations. Take the silicone concentration as the abscissa and the relative response value of the peak areas of silicone and the internal standard substance as the ordinate to establish a linear regression equation, that is, the standard curve;

[0012] S3. Take the contact lens sample to be tested, extract it, and prepare a test solution;

[0013] S4. Inject the test solution prepared in step S3 into a gas chromatograph for gas chromatographic determination. Record the relative response value of the peak areas of silicone and the internal standard substance, substitute it into the linear regression equation, and calculate the concentration of silicone in the contact lens, which is the extractable amount;

[0014] The silicone is methacryloxypropyltris(trimethylsiloxy)silane;

[0015] The internal standard substance is n-octadecane (C18);

[0016] The gas chromatographic conditions are as follows:

[0017] The stationary phase is a chromatographic column of 5% phenyl - 95% methyl polysiloxane (HP-5MS), 30 m × 250 μm × 0.25 μm; the initial column temperature is 35°C - 45°C, maintained for 1 min - 5 min, heated to 270°C - 300°C at a rate of 8°C / min - 15°C / min, and maintained for 5 min - 10 min; the carrier gas is nitrogen, the flow rate is 0.6 mL / min - 1.2 mL / min, the inlet temperature is 270°C - 290°C; the FID detector temperature: 280°C - 310°C; splitless injection, the injection volume is 0.6 μL - 1.2 μL.

[0018] In the existing technologies at home and abroad, there is no gas chromatography detection method for this silicone. Moreover, according to the comparison of different documents, even for silane-based silicone substances, their gas chromatography detection methods are not the same. For example, in documents such as "Gas Chromatographic Analysis of Vinyltri(t-butyldioxime)silane", "Chromatographic Analysis and Comprehensive Utilization of Azeotropic By-products of Silicone", and "Experimental Study on the Direct Synthesis of Dimethyldichlorosilane", completely different gas chromatography conditions are given for different types of silanes. Therefore, it is necessary to re-find suitable gas chromatography conditions to test the extractable amount of this silicone, which is the result that can only be obtained through creative labor.

[0019] In the method provided by the present invention, a reasonable and feasible detection method and detection conditions are set for the extractable methacryloxypropyltris(trimethylsiloxy)silane in the contact lens, realizing the accurate detection of the extractable amount of this silicone in the contact lens, and the detection limit can be as low as 0.04 μg / mL at the lowest.

[0020] Preferably, in step S1, the preparation method of the internal standard solution is as follows:

[0021] Weigh 25 mg of C18 into a 10 mL volumetric flask, and make up to the scale line with dichloromethane to obtain the internal standard solution.

[0022] Preferably, in step S1, the preparation method of the standard stock solution is as follows:

[0023] Weigh 25 mg of methacryloxypropyltris(trimethylsiloxy)silane into a 100 mL volumetric flask, and make up to the scale line with dichloromethane to obtain the standard stock solution.

[0024] Preferably, in step S1, the preparation method of the series of standard solutions is as follows:

[0025] Transfer 1 mL of the standard stock solution into a 100 mL volumetric flask, and make up to the scale line with dichloromethane to obtain the standard solution; respectively transfer different volumes of the standard solution into 10 mL volumetric flasks, add 4 μL of the internal standard solution respectively, and dilute to a series of standard solutions with the concentration of methacryloxypropyltris(trimethylsiloxy)silane being 0.1 μg / mL - 1.6 μg / mL with dichloromethane.

[0026] Preferably, in step S3, the preparation method of the extract is as follows:

[0027] Put the contact lens to be tested into the extraction sleeve and transfer it into the Soxhlet extractor. After adding the extraction solvent and anti-bumping glass beads to the round-bottom flask, fix it on the heating device, assemble the round-bottom flask, Soxhlet extractor and condenser in sequence, connect the water source and start the heating program, control the extraction rate and maintain a certain extraction duration. After the extraction solvent cools to room temperature, finally obtain the sample extract;

[0028] The preparation method of the blank control solution is the same as above, but the contact lens is not added.

[0029] Further preferably, the extraction solvent is any one of pure water, n-hexane or dichloromethane.

[0030] Further preferably, the number of contact lenses is 5 to 10, the volume of the extraction solvent is 100 mL to 200 mL, the extraction rate is 4 times / h to 6 times / h, and the extraction duration is 4 h to 6 h.

[0031] Preferably, in step S3, the preparation method of the test solution is as follows:

[0032] When the extraction solvent is pure water, 10 mL of each of the sample extraction solution and the blank control solution are respectively taken into a 20 mL headspace vial, 0.8 μL of the internal standard solution and 2 mL of dichloromethane are added. After extraction and standing for layering, the lower organic phase is the sample test solution and the blank test solution;

[0033] When the extraction solvent is n-hexane or dichloromethane, 0.2 mL of each of the sample extraction solution and the blank control solution are respectively taken into a 10 mL volumetric flask, 4 μL of the internal standard solution is added, and then it is made up to 10 mL with the corresponding extraction solvent to obtain the sample test solution and the blank test solution.

[0034] The beneficial effects of the present invention are as follows:

[0035] The method provided by the present invention realizes the accurate detection of the extractable amount of methacryloxypropyltris(trimethylsiloxy)silane in contact lenses, and the detection limit can be as low as 0.04 μg / mL at the lowest, making up for the relevant technical blanks at home and abroad, providing important technical support for the safety risk assessment of contact lenses, and also laying a technical foundation for pre-clinical review. Description of the Drawings

[0036] Figure 1 It is the gas chromatogram of the standard solution measured in Example 1;

[0037] Figure 2 It is the standard curve of methacryloxypropyltris(trimethylsiloxy)silane provided in Example 1. Detailed Embodiments

[0038] The present invention will be further described below in conjunction with the embodiments and the drawings.

[0039] In the specific implementation, all the reagents and experimental equipment used are commonly available commercially available reagents and experimental equipment in the art. For example, an Agilent 7890B gas chromatograph was used. The pure water was prepared by a Milli-Q water purification system. Dichloromethane was purchased from Shanghai Xingke High-Purity Solvents Co., Ltd. n-Hexane was purchased from ACS ENCO Chemical, USA. 3-(Trimethoxysilyl)propyl methacrylate and n-octadecane were purchased from TCI (Shanghai) Chemical Industry Development Co., Ltd. The specific sources of other reagents and experimental equipment are not elaborated here.

[0040] Example 1

[0041] In this example, contact lenses were used as the test samples, and the extractable amount of 3-(Trimethoxysilyl)propyl methacrylate in them was detected by the internal standard method of gas chromatography. The specific steps are as follows:

[0042] In this example, when detecting by the internal standard method of gas chromatography, the conditions of gas chromatography are as follows:

[0043] The chromatographic column with a stationary phase of 5% phenyl - 95% methyl polysiloxane (HP-5MS), 30 m × 250 μm × 0.25 μm; the initial column temperature is 40 °C, held for 2 min, heated to 300 °C at a rate of 10 °C / min, and held for 5 min; the carrier gas is nitrogen, with a flow rate of 0.9 mL / min, the inlet temperature is 280 °C; the temperature of the FID detector: 300 °C; splitless injection, and the injection volume is 1.0 μL.

[0044] S1. Preparation of a series of standard solutions

[0045] S1-1. Preparation of the internal standard solution

[0046] The internal standard used in the internal standard method is n-octadecane (C18). Weigh 25 mg of C18 into a 10 mL volumetric flask, dissolve it with dichloromethane and make up to the mark, then the internal standard solution is obtained;

[0047] S1-2. Preparation of the standard stock solution

[0048] Weigh 25 mg of 3-(Trimethoxysilyl)propyl methacrylate into a 100 mL volumetric flask, dissolve it with dichloromethane and make up to the mark, then the standard stock solution is obtained;

[0049] S1-3. Preparation of the standard solution

[0050] Transfer 1 mL of the standard stock solution into a 100 mL volumetric flask, make up to the mark with dichloromethane, then the standard solution is obtained.

[0051] S1-4. Preparation of a series of standard solutions

[0052] Transfer different volumes of the standard solution into 10 mL volumetric flasks respectively, add 4 μL of the internal standard solution, and dilute with dichloromethane to prepare a series of standard solutions with the concentration of methacryloxypropyltris(trimethylsiloxy)silane ranging from 0.1 μg / mL to 1.6 μg / mL;

[0053] S2. Gas Chromatography Test (Establishment of Standard Curve)

[0054] Inject the series of standard solutions into the gas chromatograph for testing, and obtain the chromatogram as shown in Figure 1 Establish the standard curve as shown in Figure 2 with the concentration of organosilicon as the abscissa and the relative response value of the peak area of organosilicon to the internal standard as the ordinate. The linear regression equation is y = 0.568236x + 0.0008210239, and the linear correlation coefficient is r = 0.9999. The results show that in the range of 0.1 μg / mL to 1.6 μg / mL, the linear relationship of methacryloxypropyltris(trimethylsiloxy)silane is good;

[0055] S3. Preparation of Test Solution for Contact Lenses

[0056] S3-1 Preparation of Extract

[0057] Take 6 contact lenses to be tested and put them into the extraction sleeve, then transfer them to the Soxhlet extractor. Add 180 mL of dichloromethane and anti-bumping glass beads to the round-bottom flask, fix it on the heating device, assemble the round-bottom flask, Soxhlet extractor and condenser in sequence, turn on the water source and start the heating program. The extraction rate is 4 times / h, and the extraction duration is 4 h. After the extraction solvent cools to room temperature, the sample extract is obtained. The preparation method of the blank control solution is the same as above, but without adding contact lenses;

[0058] S3-2 Preparation of Test Solution

[0059] Take 0.2 mL of the sample extract and the blank control solution respectively into 10 mL volumetric flasks, add 4 μL of the internal standard solution, and then dilute to 10 mL with dichloromethane to obtain the sample test solution and the blank test solution;

[0060] S4. Gas Chromatography Test (Test of Test Solution)

[0061] Inject the test solution into the gas chromatograph for testing, collect the relative response value of the peak area of organosilicon to the internal standard in the contact lens test solution, substitute it into the linear regression equation y = 0.568236x + 0.0008210239, and obtain the concentration of methacryloxypropyltris(trimethylsiloxy)silane in the test solution as 0.6924 μg / mL.

[0062] Experimental Example 1

[0063] Quantitation Limit and Detection Limit

[0064] The quantitative limit and detection limit of methacryloxypropyltris(trimethylsiloxy)silane were obtained by calculating the signal-to-noise ratio. The instrumental detection limit was taken as 3 times the signal-to-noise ratio, and the instrumental quantitative limit was taken as 10 times the signal-to-noise ratio. The instrumental quantitative limit of methacryloxypropyltris(trimethylsiloxy)silane was 0.1 μg / mL, and the instrumental detection limit was 0.04 μg / mL.

[0065] Experimental Example 2

[0066] Specificity test

[0067] According to Figure 1 It can be seen that the retention time of methacryloxypropyltris(trimethylsiloxy)silane was 17.735 min, and the retention time of the internal standard C18 was 19.294 min. The organosilicon and the internal standard could be completely separated, and the blank test solution had no interference, indicating that the method had good specificity.

[0068] Experimental Example 3

[0069] Precision test

[0070] According to the steps provided in step S1-4 of Example 1, standard solutions with three concentrations of 0.11 μg / mL, 0.64 μg / mL, and 1.29 μg / mL were prepared. Each concentration of the standard solution was injected continuously for 6 times, and the relative standard deviation (RSD) of the relative response value was calculated. The test results are shown in Table 1.

[0071] Table 1 Precision

[0072]

[0073]

[0074] It can be seen from the data in Table 1 that the RSD values of the organosilicon were in the range of 0.1% - 1.2%, all meeting the requirements specified in Part IV 9101 of the Pharmacopoeia of the People's Republic of China (2020 Edition), indicating that the method provided by the present invention had good precision.

[0075] Experimental Example 4

[0076] Accuracy test

[0077] 1) Using pure water as the extraction solvent: Accurately pipette 10 mL of the pure water blank control solution into a 20 mL headspace vial, add 0.51 mL of the standard solution and 0.8 μL of the internal standard solution, vortex and mix well. Accurately add 2 mL of dichloromethane, vortex extract and let it stand for stratification, then take the upper organic phase for injection analysis.

[0078] 2) Using dichloromethane as the extraction solvent: Accurately pipette 0.20 mL of the dichloromethane sample extract into a 10 mL volumetric flask, add 2.55 mL of the standard solution and 4 μL of the internal standard solution, dilute to 10 mL with dichloromethane, and perform injection analysis.

[0079] 3) Using n-hexane as the extraction solvent: Accurately pipette 0.20 mL of the n-hexane sample extract into a 10 mL volumetric flask, add 2.55 mL of the standard solution and 4 μL of the internal standard solution, dilute to 10 mL with n-hexane, and perform injection analysis.

[0080] For each recovery rate test, inject 6 needles continuously, calculate the average recovery rate and relative standard deviation (RSD) of silicone, and the results are shown in Table 2.

[0081] Table 2 Accuracy

[0082]

[0083] As can be seen from the data in Table 2, the average recovery rate of silicone is in the range of 94.8% - 104.5%, and the RSD value is in the range of 1.7% - 3.7%, meeting the requirements specified in Part 4, 9101 of the Pharmacopoeia of the People's Republic of China (2020 Edition), indicating that the method provided by the present invention has good accuracy.

Claims

1. A method for determining the extractable amount of silicone in a contact lens, characterized in that: The steps include: S1. Preparation of series of standard solutions Dissolve the internal standard substance in dichloromethane to obtain an internal standard solution, dissolve the organosilicon standard substance in dichloromethane to obtain a standard stock solution, and prepare a series of standard solutions with concentrations of 0.1 μg / mL-1.6 μg / mL using the internal standard solution and the standard stock solution, wherein the internal standard concentration is 1 μg / mL; S2. Establishing a standard curve The series of standard solutions prepared in step S1 are injected into a gas chromatograph for gas chromatography determination, and the relative response values ​​of the peak areas of organosilicon and the internal standard substance in the series of standard solutions with different concentrations are respectively determined, and a linear regression equation, i.e., a standard curve, is established with the organosilicon concentration as the abscissa and the relative response value of the peak areas of organosilicon and the internal standard substance as the ordinate; S3. Take the contact lens to be tested, extract it and prepare the test solution; S4. Inject the test solution prepared in step S3 into a gas chromatograph for gas chromatography measurement, record the relative response value of the peak area of ​​the organic silicon and the internal standard, substitute it into the linear regression equation, and calculate the concentration of the organic silicon in the contact lens, which is the extractable amount; The silicone is methacryloxypropyl tris(trimethylsiloxy)silane; The internal standard was n-octadecane; The gas chromatography conditions were as follows: The stationary phase is an HP-5MS chromatographic column, 30m×250μm×0.25μm; the initial column temperature is 35℃~45℃, maintained for 1min~5min, heated to 270℃~300℃ at 8℃ / min~15℃ / min, and maintained for 5min~10min; the carrier gas is nitrogen, the flow rate is 0.6mL / min~1.2mL / min, the injection port temperature is 270℃~290℃; FID detector temperature: 280℃~310℃; non-split injection, the injection volume is 0.6μL~1.2μL.

2. The method according to claim 1, characterized in that In step S1, the preparation method of internal standard solution is as follows: Weigh 25 mg of C18 into a 10 mL volumetric flask and dilute to the mark with dichloromethane to obtain the internal standard solution.

3. The method according to claim 2, characterized in that In step S1, the preparation method of the standard stock solution is as follows: Weigh 25 mg of methacryloyloxypropyl tris(trimethylsiloxy)silane into a 100 mL volumetric flask and dilute to the mark with dichloromethane to obtain a standard stock solution.

4. The method according to claim 3, characterized in that In step S1, the preparation method of the series of standard solutions is as follows: Pipette 1 mL of standard stock solution into a 100 mL volumetric flask, dilute to the mark with dichloromethane to obtain a standard solution; pipette different volumes of standard solution into 10 mL volumetric flasks, add 4 μL of internal standard solution respectively, and dilute with dichloromethane to a series of standard solutions with a concentration of 0.1 μg / mL to 1.6 μg / mL.

5. The method according to claim 1, characterized in that In step S3, the extract is prepared as follows: Place the contact lens to be tested into the extraction sleeve and transfer it to the Soxhlet extractor. After adding the extraction solvent and anti-boiling glass beads into the round-bottom flask, fix it on the heating device, assemble the round-bottom flask, Soxhlet extractor and condenser in sequence, connect the water source and start the heating program, control the extraction rate and maintain a certain extraction time, and finally obtain the sample extract after the extraction solvent is cooled to room temperature; The blank control solution was prepared in the same manner as above, but without the addition of contact lenses.

6. The method according to claim 5, characterized in that The extraction solvent is any one of pure water, n-hexane or dichloromethane.

7. The method according to claim 5, characterized in that The number of contact lenses is 5 to 10, the volume of the extraction solvent is 100 mL to 200 mL, the extraction rate is 4 times / h to 6 times / h, and the extraction time is 4 h to 6 h.

8. The method according to claim 6, characterized in that In step S3, the test solution is prepared as follows: When pure water is used as the extraction solvent, take 10 mL of the sample extract and blank solution respectively in a 20 mL headspace bottle, add 0.8 μL of internal standard solution and 2 mL of dichloromethane, extract and stand for stratification, and the lower organic phase is the sample test solution and the blank test solution; When n-hexane or dichloromethane is used as the extraction solvent, take 0.2 mL of the sample extract and blank control solution respectively into a 10 mL volumetric flask, add 4 μL of the internal standard solution, and then dilute to 10 mL with the corresponding extraction solvent to obtain the sample test solution and blank test solution.

Images