CN117783314A - Method for measuring sulfur and 14 antioxidant additives in medical rubber plug - Google Patents
Method for measuring sulfur and 14 antioxidant additives in medical rubber plug Download PDFInfo
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- CN117783314A CN117783314A CN202311599900.8A CN202311599900A CN117783314A CN 117783314 A CN117783314 A CN 117783314A CN 202311599900 A CN202311599900 A CN 202311599900A CN 117783314 A CN117783314 A CN 117783314A
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- 239000003963 antioxidant agent Substances 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 30
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 239000011593 sulfur Substances 0.000 title claims abstract description 25
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 25
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 39
- 239000007788 liquid Substances 0.000 claims abstract description 22
- 239000000523 sample Substances 0.000 claims abstract description 22
- 239000012488 sample solution Substances 0.000 claims abstract description 12
- 239000012224 working solution Substances 0.000 claims abstract description 11
- 238000010812 external standard method Methods 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 12
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- CFXCGWWYIDZIMU-UHFFFAOYSA-N Octyl-3,5-di-tert-butyl-4-hydroxy-hydrocinnamate Chemical compound CCCCCCCCOC(=O)CCC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 CFXCGWWYIDZIMU-UHFFFAOYSA-N 0.000 claims description 7
- JKIJEFPNVSHHEI-UHFFFAOYSA-N Phenol, 2,4-bis(1,1-dimethylethyl)-, phosphite (3:1) Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=CC=C1OP(OC=1C(=CC(=CC=1)C(C)(C)C)C(C)(C)C)OC1=CC=C(C(C)(C)C)C=C1C(C)(C)C JKIJEFPNVSHHEI-UHFFFAOYSA-N 0.000 claims description 7
- BGYHLZZASRKEJE-UHFFFAOYSA-N [3-[3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoyloxy]-2,2-bis[3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoyloxymethyl]propyl] 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CCC(=O)OCC(COC(=O)CCC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)(COC(=O)CCC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)COC(=O)CCC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)=C1 BGYHLZZASRKEJE-UHFFFAOYSA-N 0.000 claims description 7
- 239000002035 hexane extract Substances 0.000 claims description 7
- SSDSCDGVMJFTEQ-UHFFFAOYSA-N octadecyl 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 SSDSCDGVMJFTEQ-UHFFFAOYSA-N 0.000 claims description 7
- QSRJVOOOWGXUDY-UHFFFAOYSA-N 2-[2-[2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propanoyloxy]ethoxy]ethoxy]ethyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propanoate Chemical compound CC(C)(C)C1=C(O)C(C)=CC(CCC(=O)OCCOCCOCCOC(=O)CCC=2C=C(C(O)=C(C)C=2)C(C)(C)C)=C1 QSRJVOOOWGXUDY-UHFFFAOYSA-N 0.000 claims description 6
- WJQOZHYUIDYNHM-UHFFFAOYSA-N 2-tert-Butylphenol Chemical compound CC(C)(C)C1=CC=CC=C1O WJQOZHYUIDYNHM-UHFFFAOYSA-N 0.000 claims description 6
- HCILJBJJZALOAL-UHFFFAOYSA-N 3-(3,5-ditert-butyl-4-hydroxyphenyl)-n'-[3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoyl]propanehydrazide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CCC(=O)NNC(=O)CCC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)=C1 HCILJBJJZALOAL-UHFFFAOYSA-N 0.000 claims description 6
- PVFQHGDIOXNKIC-UHFFFAOYSA-N 4-[2-[3-[2-(4-hydroxyphenyl)propan-2-yl]phenyl]propan-2-yl]phenol Chemical compound C=1C=CC(C(C)(C)C=2C=CC(O)=CC=2)=CC=1C(C)(C)C1=CC=C(O)C=C1 PVFQHGDIOXNKIC-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 6
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 6
- 239000011550 stock solution Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 238000010828 elution Methods 0.000 claims description 4
- 238000010298 pulverizing process Methods 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 238000005520 cutting process Methods 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000005259 measurement Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 239000012085 test solution Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 238000001514 detection method Methods 0.000 abstract description 18
- 238000004811 liquid chromatography Methods 0.000 abstract description 6
- 230000004907 flux Effects 0.000 abstract description 3
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 2
- 238000010586 diagram Methods 0.000 description 7
- 239000012086 standard solution Substances 0.000 description 4
- 229930185605 Bisphenol Natural products 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- -1 bisphenol a Chemical compound 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000009512 pharmaceutical packaging Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
Landscapes
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention discloses a method for measuring sulfur and 14 antioxidant additives in a medicinal rubber plug, which relates to the technical field of material detection and has the technical key points that: the method comprises the following steps: s1, preparing a sample to obtain a sample solution; s2, preparing a standard working solution; s3, measuring a standard working solution and a sample solution by using a liquid chromatograph, automatically drawing a standard curve by using chromatographic software, and quantitatively analyzing the content of the to-be-detected object in the sample solution by using an external standard method; s4, calculating the content of the sample to be measured by adopting a formula. The method can detect sulfur in the rubber plug and the antioxidant in the rubber plug 14 at the same time, so that the flux problem of detecting the antioxidant in the rubber plug by liquid chromatography is greatly improved; meanwhile, the method greatly reduces the problem of high cost caused by detection by adopting a high performance liquid chromatography tandem mass spectrometer; in addition, the invention has great popularization value for basic layers or enterprises, and effectively reduces the related detection cost.
Description
Technical Field
The invention relates to the technical field of material detection, in particular to a method for measuring sulfur and 14 antioxidant additives in a medicinal rubber plug.
Background
Rubber is widely used in the pharmaceutical industry because of its excellent properties, such as being processed into seal assemblies for pharmaceutical packaging. The rubber contains unsaturated double bonds, and environmental factors (light, heat, oxygen and the like) can cause the aging of rubber components and shorten the service life of the rubber components. For this reason, synthetic antioxidants are often used as protective additives for rubber seal components. The combination of the antioxidant and the rubber molecule is a physical combination, and the rubber seal assembly can migrate into the medicine from the antioxidant during use, and can be further ingested by a human body. The immigrants of antioxidants are difficult to find in a short time and have a latent nature to the harm of the human body. Relevant administrative departments and research institutions at home and abroad have formulated and issued regulations, standards and guidelines to strictly regulate the quality of rubber plugs. These regulations only specify the basic requirements for the production, use and quality control of the seals, while lacking limits on the antioxidant content of the rubber stopper and lacking detection methods for the detection of antioxidants.
By searching, the existing detection method of the antioxidants in the rubber plug is mainly carried out by adopting liquid phase and liquid chromatography mass spectrometry, the existing detection method adopting liquid chromatography is few in detection types, the detection types of the antioxidants adopting liquid quality method can reach more than ten types, but the use cost and the purchase cost of the liquid quality are much higher than those of the liquid phase, and meanwhile, the sulfur content in the rubber plug cannot be detected by the liquid quality.
Therefore, the invention aims to provide a method for measuring sulfur and 14 antioxidant additives in a medicinal rubber plug so as to solve the problems.
Disclosure of Invention
The invention aims to solve the problems that in the prior art, the detection types of antioxidants in a rubber plug are fewer, the use cost and the purchase cost of liquid are much higher than those of liquid, and meanwhile, the liquid can not detect the sulfur content in the rubber plug, and provides a method for measuring sulfur and 14 antioxidant additives in a medicinal rubber plug.
In order to achieve the above purpose, the technical scheme of the invention is as follows:
the invention provides a method for measuring sulfur and 14 antioxidant additives in a medicinal rubber plug, which comprises the following steps:
s1, sample preparation
S1-1, cutting a proper amount of a medicine rubber plug into particles with the size of 2-3 mm; after liquid nitrogen embrittlement treatment, pouring the mixture into a high-speed pulverizer to pulverize for about 1 minute, continuously adopting the liquid nitrogen embrittlement, pulverizing the mixture into fine and uniform particles by the high-speed pulverizer, and drying the particles at 60 ℃ for 1 hour to obtain a pulverized sample;
s1-2, accurately weighing 1.0g of a sample, placing in a 50mL centrifuge tube, adding 10mL of n-hexane, uniformly mixing by vortex, ultrasonically extracting for 60min, and standing to room temperature; taking n-hexane extract in a 10mL measuring flask, and fixing the volume to the scale; taking 1.0mL of n-hexane extract, concentrating to near dryness at 40 ℃ with nitrogen, and adding 1.0mL of methanol for dissolution to obtain a sample solution;
s2, preparation of standard working solution
Adopting methanol to dilute the standard stock solution step by step to prepare a standard working solution;
s3, measurement
Measuring standard working solution and sample solution by using a liquid chromatograph, automatically drawing a standard curve by using chromatographic software, and quantitatively analyzing the content of the to-be-detected object in the sample solution by using an external standard method;
s4, calculating
The content of the sample to be measured is calculated by adopting the following formula:
wherein: x represents the content of the sample to be detected, and the unit is: mg/kg;
c represents the measured value of the test solution, and the unit is: μg/mL;
v represents the constant volume, the unit is: mL;
m represents the mass of the sample, and the unit is: g.
further, the preparation method of the standard stock solution in the step S2 is as follows:
respectively weighing about 10mg of TBHQ, bisphenol A, 2-tertiary butyl phenol, bisphenol M, antioxidant 245, antioxidant 1024, antioxidant 246, antioxidant 1135, antioxidant 3114, antioxidant 1010, antioxidant 1330 and antioxidant 1076 standard substances, dissolving by adopting acetone, fixing the volume to 10mL, shaking uniformly, and preserving at 0-4 ℃ in a dark place;
about 10mg of standard products of sulfur, antioxidant 300 and antioxidant 168 are respectively weighed, dissolved by methylene dichloride and fixed to 10mL, and the mixture is uniformly shaken and stored at 0-4 ℃ in a dark place.
Further, the working conditions of the liquid chromatograph in step S3 are:
(a) Chromatographic column: agilent Eclipse XDB-C8, 4.6X105 mm,5.0 μm;
(b) Wavelength: 274nm;
(c) Flow rate: 1mL/min;
(d) Sample injection amount: 10. Mu.L;
(e) Column temperature: 35 ℃;
(f) Mobile phase: methanol: gradient elution with water (0.1% formic acid).
Compared with the prior art, the beneficial effect of this scheme:
1. according to the scheme, the sulfur in the rubber plug and the antioxidant in the rubber plug 14 can be detected simultaneously by optimizing and combining chromatographic conditions, extraction methods and the like, so that the problem of flux of the antioxidant in the rubber plug detected by liquid chromatography is greatly improved;
2. the method of the invention greatly reduces the problem of high cost caused by detection by adopting a high performance liquid chromatography tandem mass spectrometer; in addition, the method has great popularization value for basic layers or enterprises, and effectively reduces the related detection cost.
Drawings
FIG. 1 is a chromatogram in an embodiment of the invention;
FIG. 2 is a TBHQ-linear graph in an embodiment of the invention;
FIG. 3 is a bisphenol A-linear graph in an embodiment of the present invention;
FIG. 4 is a 2-tert-butylphenol-linear graph according to an embodiment of the present invention;
FIG. 5 is a graph of bisphenol M-linearity in an embodiment of the present invention;
FIG. 6 is a graph showing antioxidant 245-linearity in an embodiment of the present invention;
FIG. 7 is a graph of antioxidant 300-linearity in an embodiment of the present invention;
FIG. 8 is a 1024-linear diagram of an antioxidant in an embodiment of the present invention;
FIG. 9 is a graph of antioxidant 246-linearity in an embodiment of the present invention;
FIG. 10 is a sulfur-linear plot in an embodiment of the invention;
FIG. 11 is a linear diagram of antioxidant 1135 in an embodiment of the present invention;
FIG. 12 is a linear diagram of an antioxidant 3114 in an embodiment of the invention;
FIG. 13 is a linear diagram of an antioxidant 1010 in an embodiment of the present invention;
FIG. 14 is a linear diagram of antioxidant 1330 in an embodiment of the present invention;
FIG. 15 is a linear diagram of an antioxidant 1076 in an embodiment of the present invention;
fig. 16 is a linear diagram of antioxidant 168 in an embodiment of the present invention.
Detailed Description
In order that those skilled in the art will better understand the present invention, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings, wherein it is to be understood that the illustrated embodiments are merely exemplary of some, but not all, of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, shall fall within the scope of the present invention.
It should be noted that, without conflict, the embodiments of the present invention and features of the embodiments may be combined with each other. The present invention will be described in detail with reference to examples.
Examples:
the scheme provided by the embodiment of the invention is as described in the above summary of the invention, and provides a method for measuring sulfur and 14 antioxidant additives in a medical rubber plug, which is used for detecting sulfur and antioxidant additives in rubber products, such as detecting sulfur and 14 antioxidant additives in the medical rubber plug. The specific implementation process of the measuring method is as follows:
1. range of
The operation flow of the measuring method is suitable for measuring sulfur, TBHQ, bisphenol A, 2-tertiary butyl phenol, bisphenol M, antioxidant 245, antioxidant 300, antioxidant 1024, antioxidant 246, antioxidant 1135, antioxidant 3114, antioxidant 1010, antioxidant 1330, antioxidant 1076 and antioxidant 168 in the medical rubber plug.
2. Principle of
Pulverizing medicinal rubber plug, extracting with n-hexane, detecting by liquid chromatography, and quantifying by external standard method.
3. Reagent(s)
3.1 methanol: chromatographic purity;
3.2 n-hexane: chromatographic purity;
3.3 acetone: chromatographic purity;
3.4 dichloromethane: chromatographic purity;
3.5 liquid nitrogen: storing in a liquid nitrogen tank;
3.6 sulfur, TBHQ, bisphenol a, 2-t-butylphenol, bisphenol M, antioxidant 245, antioxidant 300, antioxidant 1024, antioxidant 246, antioxidant 1135, antioxidant 3114, antioxidant 1010, antioxidant 1330, antioxidant 1076, antioxidant 168 standard: the purity is more than or equal to 95 percent;
3.7 standard stock: about 10mg of TBHQ, bisphenol A, 2-tertiary butyl phenol, bisphenol M, antioxidant 245, antioxidant 1024, antioxidant 246, antioxidant 1135, antioxidant 3114, antioxidant 1010, antioxidant 1330 and antioxidant 1076 standard substances are respectively weighed, dissolved by acetone, fixed to volume to 10mL, uniformly shaken and stored at 0-4 ℃ in a dark place. About 10mg of standard products of sulfur, antioxidant 300 and antioxidant 168 are respectively weighed, dissolved by methylene dichloride and fixed to 10mL, shaken uniformly and stored in a dark place at 0-4 ℃.
4. Apparatus and device
4.1 Siemens flywheel Multimate 3000 liquid chromatograph, diode Array Detector (DAD). The working conditions of the liquid chromatograph are as follows:
(a) Chromatographic column: agilent Eclipse XDB-C8, 4.6X105 mm,5.0 μm;
(b) Wavelength: 274nm;
(c) Flow rate: 1mL/min;
(d) Sample injection amount: 10. Mu.L;
(e) Column temperature: 35 ℃;
(f) Mobile phase: methanol: gradient elution with water (0.1% formic acid) was performed with the procedure shown in table 1 below;
table 1 liquid chromatography gradient elution procedure
4.2 parts per million balance;
4.3 parts per million balance;
4.4 high speed pulverizer;
4.5 an ultrasonic cleaner;
4.6 vortex mixer;
4.7 nitrogen blowing instrument;
5. analytical procedure
5.1 sample preparation
And (5) taking a proper amount of the rubber plug for medicine, and cutting into particles with the size of 2-3 mm. After liquid nitrogen embrittlement treatment, pouring the mixture into a high-speed pulverizer to pulverize for about 1 minute, continuously adopting the liquid nitrogen embrittlement, pulverizing the mixture into fine and uniform particles by the high-speed pulverizer, and drying the particles at 60 ℃ for 1 hour to obtain a pulverized sample. 1.0g of sample is precisely weighed, placed in a 50mL centrifuge tube, 10mL of normal hexane is added, vortex mixed evenly, extracted by ultrasonic for 60min and cooled to room temperature. Taking n-hexane extract, and putting the n-hexane extract in a 10mL measuring flask to fix the volume to the scale. Taking 1.0mL of n-hexane extract, concentrating to near dryness at 40 ℃ with nitrogen, and adding 1.0mL of methanol for dissolution to obtain a sample solution.
5.2 preparation of Standard working solution
Standard working solutions were prepared by stepwise dilution of standard stock solutions (prepared as described in 3.7 above) with methanol, the linear range and correlation coefficients are shown in table 2 below.
TABLE 2 Sulfur and 14 antioxidants Linear Range, linear equation, correlation coefficient in pharmaceutical rubber plug
5.3 measurement
And measuring standard working solution and sample solution by using a liquid chromatograph, automatically drawing a standard curve by using chromatographic software, and quantitatively analyzing the content of the to-be-detected object in the sample solution by using an external standard method.
6. Calculation of
Wherein:
x represents the content of the sample to be detected, and the unit is: mg/kg;
c represents the measured value of the test solution, and the unit is: μg/mL;
v represents the constant volume, the unit is: mL;
m represents the mass of the sample, and the unit is: g.
7. quality control
7.1 Linear Range and correlation coefficient
The linear ranges of sulfur, TBHQ, bisphenol A, 2-t-butylphenol, bisphenol M, antioxidant 245, antioxidant 300, antioxidant 1024, antioxidant 246, antioxidant 1135, antioxidant 3114, antioxidant 1010, antioxidant 1330, antioxidant 1076, and antioxidant 168 in the process of the present invention are shown in Table 2.
7.2 detection and quantification limits
And (3) gradually diluting the standard solution according to the response value of the standard solution, taking the standard solution concentration with the signal to noise ratio equal to about 3 as a detection limit, and taking the standard solution concentration with the signal to noise ratio equal to about 10 as a quantification limit. The detection limit and the quantitative limit of the method are shown in Table 2.
Compared with the prior art, the measuring method can simultaneously detect sulfur in the rubber plug and the antioxidant in 14 by optimizing and combining chromatographic conditions, extraction methods and the like, and greatly improves the flux problem of detecting the antioxidant in the rubber plug by liquid chromatography; meanwhile, the method greatly reduces the problem of high cost caused by detection by adopting a high performance liquid chromatography tandem mass spectrometer; in addition, the method has great popularization value for basic layers or enterprises, and effectively reduces the related detection cost.
The above specific embodiments are provided for illustrative purposes only and are not intended to limit the invention, and modifications, no inventive contribution, will be made to the embodiments by those skilled in the art after having read the present specification, as long as they are within the scope of the patent statutes.
Claims (3)
1. The method for measuring sulfur and 14 antioxidant additives in the medical rubber plug is characterized by comprising the following steps: the method comprises the following steps:
s1, sample preparation
S1-1, cutting a proper amount of a medicine rubber plug into particles with the size of 2-3 mm; after liquid nitrogen embrittlement treatment, pouring the mixture into a high-speed pulverizer to pulverize for about 1 minute, continuously adopting the liquid nitrogen embrittlement, pulverizing the mixture into fine and uniform particles by the high-speed pulverizer, and drying the particles at 60 ℃ for 1 hour to obtain a pulverized sample;
s1-2, accurately weighing 1.0g of a sample, placing in a 50mL centrifuge tube, adding 10mL of n-hexane, uniformly mixing by vortex, ultrasonically extracting for 60min, and standing to room temperature; taking n-hexane extract in a 10mL measuring flask, and fixing the volume to the scale; taking 1.0mL of n-hexane extract, concentrating to near dryness at 40 ℃ with nitrogen, and adding 1.0mL of methanol for dissolution to obtain a sample solution;
s2, preparation of standard working solution
Adopting methanol to dilute the standard stock solution step by step to prepare a standard working solution;
s3, measurement
Measuring standard working solution and sample solution by using a liquid chromatograph, automatically drawing a standard curve by using chromatographic software, and quantitatively analyzing the content of the to-be-detected object in the sample solution by using an external standard method;
s4, calculating
The content of the sample to be measured is calculated by adopting the following formula:
wherein: x represents the content of the sample to be detected, and the unit is: mg/kg;
c represents the measured value of the test solution, and the unit is: μg/mL;
v represents the constant volume, the unit is: mL;
m represents the mass of the sample, and the unit is: g.
2. the method for determining sulfur and 14 antioxidant additives in a medical rubber plug as claimed in claim 1, wherein the method comprises the following steps: the preparation method of the standard stock solution in the step S2 comprises the following steps:
respectively weighing about 10mg of TBHQ, bisphenol A, 2-tertiary butyl phenol, bisphenol M, antioxidant 245, antioxidant 1024, antioxidant 246, antioxidant 1135, antioxidant 3114, antioxidant 1010, antioxidant 1330 and antioxidant 1076 standard substances, dissolving by adopting acetone, fixing the volume to 10mL, shaking uniformly, and preserving at 0-4 ℃ in a dark place;
about 10mg of standard products of sulfur, antioxidant 300 and antioxidant 168 are respectively weighed, dissolved by methylene dichloride and fixed to 10mL, and the mixture is uniformly shaken and stored at 0-4 ℃ in a dark place.
3. The method for determining sulfur and 14 antioxidant additives in a medical rubber plug as claimed in claim 1, wherein the method comprises the following steps: the working conditions of the liquid chromatograph in the step S3 are as follows:
(a) Chromatographic column: agilent Eclipse XDB-C8, 4.6X105 mm,5.0 μm;
(b) Wavelength: 274nm;
(c) Flow rate: 1mL/min;
(d) Sample injection amount: 10. Mu.L;
(e) Column temperature: 35 ℃;
(f) Mobile phase: methanol: gradient elution with water (0.1% formic acid).
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311599900.8A CN117783314A (en) | 2023-11-28 | 2023-11-28 | Method for measuring sulfur and 14 antioxidant additives in medical rubber plug |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311599900.8A CN117783314A (en) | 2023-11-28 | 2023-11-28 | Method for measuring sulfur and 14 antioxidant additives in medical rubber plug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117783314A true CN117783314A (en) | 2024-03-29 |
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ID=90400878
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311599900.8A Pending CN117783314A (en) | 2023-11-28 | 2023-11-28 | Method for measuring sulfur and 14 antioxidant additives in medical rubber plug |
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| Country | Link |
|---|---|
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