Method for detecting content of trichlorotert-butyl alcohol in packing material

Abstract

The invention discloses a method for detecting the content of trichlorotert-butyl alcohol in a packing material, and relates to the technical field of medicines. The detection method comprises the following steps: cutting a to-be-detected packing material into pieces, putting the cut to-be-detected packing material into a headspace bottle, adding a solvent into the headspace bottle, and then sealing the headspace bottle without soaking the to-be-detected packing material for a certain time; and detecting the gas in the headspace bottle by headspace-gas chromatography to obtain the content of trichlorotert-butyl alcohol in the to-be-detected packing material. The method is a method for directly detecting the trichlorotert-butyl alcohol in the packing material, and has the advantages of simplicity in sample treatment, short detection time, small operation error and the like.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a method for detecting the content of chlorobutanol in a packaging material. Background Art

[0002] Chlorobutanol is an alcohol antibacterial agent that has the effect of inhibiting bacteria and molds. Its principle is to coagulate bacterial proteins and protein balls. Chlorobutanol is often added to eye drops as a pharmaceutical excipient. However, chlorobutanol is volatile and easy to sublimate. After being stored for a certain period of time, the content of chlorobutanol in eye drops will decrease to varying degrees, often resulting in unqualified product content. Commonly used eye drops packaging bottles are mostly high molecular polymers. When the liquid medicine is filled into the bottle, the chlorobutanol molecules will be adsorbed on the surface of the packaging material and even embedded in the molecular gaps of the packaging material, resulting in a decrease in the content of chlorobutanol in the liquid medicine. There are literature reports that low-density polyethylene medicinal eye drop bottles have an adsorption effect on chlorobutanol, so this factor is one of the possible reasons for the reduction of chlorobutanol content in the product.

[0003] The existing method for detecting chlorobutanol is mainly for raw material samples, using gas chromatography, with a capillary column with polyethylene glycol (PEG-20M or its variant with similar polarity) as the stationary liquid as the chromatographic column; the starting temperature is 35°C, maintained for 5 minutes, and the temperature is increased to 135°C at a rate of 20°C per minute, and maintained for 10 minutes; the injection port temperature is 260°C; the detector temperature is 280°C, 2,2,2-trichloroethanol is used as the internal standard, and n-hexane is used as the solvent to detect the content of chlorobutanol in the sample, but this method is not suitable for the adsorption of chlorobutanol by the packaging material. There are documents that use different solvents to soak the packaging material for 7 days to detect the content of chlorobutanol in the soaking solution, but the detection method has the disadvantages of being time-consuming and complicated to operate. There are very few methods for directly detecting chlorobutanol in the packaging material. Summary of the invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art or related art.

[0005] To this end, the present invention provides a method for detecting the content of chlorobutanol in a packaging material, comprising:

[0006] Sample preparation: Cut the packaging material to be tested into pieces and put them into a headspace bottle, add a solvent into the headspace bottle, and then cap the headspace bottle, without soaking the packaging material to be tested for a certain period of time;

[0007] Headspace-gas chromatography detection: The gas in the headspace bottle is detected by headspace-gas chromatography to obtain the content of chlorobutanol in the packaging material to be tested.

[0008] Furthermore, the solvent is an ethanol aqueous solution with a mass fraction of 5% to 10%, preferably a 10% ethanol aqueous solution.

[0009] Furthermore, in the headspace-gas chromatography method, the headspace conditions are: heating temperature 85°C to 90°C, equilibration time 50min to 60min; quantitative loop temperature 98°C to 102°C, and transfer line temperature 105°C to 115°C.

[0010] Furthermore, when the detection method extracts chlorobutanol from the packaging material to be tested, the extraction error is less than 5%.

[0011] Furthermore, in the headspace-gas chromatography method, the injection port temperature of the gas chromatography is 210°C to 230°C.

[0012] Furthermore, in the headspace-gas chromatography method, the chromatographic column of the gas chromatography is: (5%-phenyl)-methylpolysiloxane capillary column, with a length of 30m×inner diameter of 0.32mm, a film thickness of 0.25μm, and a flow rate of 1.5mL / min.

[0013] Furthermore, in the headspace-gas chromatography method, the temperature rising program of the chromatographic column is: initial temperature 55°C~65°C, maintained for 8min~12min, then increased to 140°C~160°C at 18°C / min~22°C / min, maintained for 2min~4min, then increased to 220°C~240°C at 45°C / min~55°C / min, maintained for 2min~4min.

[0014] Furthermore, in the headspace-gas chromatography method, the detector of the gas chromatography is a hydrogen flame ionization detector, and the temperature of the detector is 245°C to 255°C.

[0015] Furthermore, in the headspace-gas chromatography method, the carrier gas is nitrogen, the headspace injection duration is 28s to 32s, and the gas chromatography cycle time is 25min to 27min.

[0016] Furthermore, the packaging material is a polypropylene medicinal eye drop bottle or a polyethylene medicinal eye drop bottle.

[0017] Compared with the prior art, the present invention has at least the following beneficial effects:

[0018] The method for detecting the content of chlorobutanol in a packaging material provided by the present invention adopts head space-gas chromatography to detect the content of chlorobutanol adsorbed in the packaging material. The method is a method for directly detecting chlorobutanol in the packaging material, that is, when preparing the sample, the packaging material to be tested does not need to be immersed for a certain period of time, and the head space-gas chromatography can be used to detect the gas in the head space bottle. The method has the advantages of simple sample processing, short detection time, small operation error, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The linear result graph of chlorobutanol in a polypropylene medicinal eye drop bottle using the head space-gas chromatography method of the present invention is provided in an embodiment of the present invention.

[0020] Figure 2 The gas chromatogram of the reference substance in the repeatability results provided in the embodiments of the present invention.

[0021] Figure 3 The gas chromatogram of the repetitive sample in the repetitive results provided in the embodiments of the present invention. DETAILED DESCRIPTION

[0022] In order to better understand the above technical solution, the technical solution of the present invention is described in detail below through specific embodiments.

[0023] The embodiment of the present invention provides a method for detecting the content of chlorobutanol in a packaging material, comprising:

[0024] (1) Sample preparation: Cut the packaging material to be tested into pieces and put them into a headspace bottle, add a solvent into the headspace bottle, and then seal the headspace bottle without soaking the packaging material to be tested for a certain period of time;

[0025] The solvent is an ethanol aqueous solution with a mass fraction of 5% to 10%, preferably a 10% ethanol aqueous solution. The packaging material to be tested is a polypropylene medicinal eye drop bottle or a polyethylene medicinal eye drop bottle, and the polyethylene medicinal eye drop bottle is a low-density polyethylene medicinal eye drop bottle or a high-density polyethylene medicinal eye drop bottle.

[0026] (2) Head space-gas chromatography detection: The gas in the head space bottle is detected by head space-gas chromatography to obtain the content of chlorobutanol in the packaging material to be tested.

[0027] Among them, in headspace-gas chromatography:

[0028] The injection method is headspace injection, the carrier gas is nitrogen, and the headspace injection duration is 28s to 32s, preferably, the headspace injection duration is 30s.

[0029] Headspace conditions: heating temperature 85°C to 90°C, equilibration time 50min to 60min; preferably, heating temperature 85°C, equilibration time 60min. Quantitative loop temperature 98°C to 102°C, transfer line temperature 105°C to 115°C; preferably, quantitative loop temperature 100°C, transfer line temperature 110°C.

[0030] Chromatographic conditions: The injection port temperature of the gas chromatograph is 210° C. to 230° C., preferably 220° C. The carrier gas is nitrogen.

[0031] The chromatographic column of the gas chromatography is: (5%-phenyl)-methyl polysiloxane capillary column, length 30m×inner diameter 0.32mm, film thickness 0.25μm, flow rate 1.5mL / min. Optionally, the chromatographic column is Agilent's HP-5, Thermo Fisher's TG-5, Shimadzu's SH-5, etc.

[0032] The temperature raising program of the chromatographic column is as follows: initial temperature 55°C-65°C, maintained for 8-12 min, then increased to 140°C-160°C at 18°C / min-22°C / min, maintained for 2-4 min, then increased to 220°C-240°C at 45°C / min-55°C / min, maintained for 2-4 min; preferably, the initial temperature is 60°C, maintained for 10 min, then increased to 150°C at 20°C / min, maintained for 3 min, then increased to 230°C at 50°C / min, maintained for 2 min.

[0033] The detector of the gas chromatography is a hydrogen flame ionization detector, the temperature of the detector is 245°C to 255°C, and the preferred detection temperature is 250°C.

[0034] The gas chromatography cycle time is 25min to 27min.

[0035] The method for detecting the content of chlorobutanol in a packaging material provided by an embodiment of the present invention uses head space-gas chromatography to detect the content of chlorobutanol adsorbed in the packaging material. It is a method for directly detecting chlorobutanol in the packaging material, that is, when preparing the sample, there is no need to soak the packaging material to be tested for a certain period of time, and the head space-gas chromatography can be used to detect the gas in the head space bottle. The method has the advantages of simple sample processing, short detection time, small operation error, etc.

[0036] Specifically, the detection method of chlorobutanol content in the packaging material provided by the embodiment of the present invention has the following beneficial effects: 1. The detection method is headspace-gas chromatography, which flexibly uses the headspace sampling method of the gas chromatograph. 2. The pretreatment of the packaging material is simple and time-consuming; only the packaging material to be tested needs to be taken, the liquid medicine is poured out, the ultrapure water is rinsed and wiped dry, the bottle body and the bottle stopper are cut into pieces, and put into the headspace bottle, and 5% to 10% ethanol aqueous solution is accurately transferred thereto, and the headspace bottle is capped. There is no need to soak the packaging material to be tested for a certain period of time, and the chlorobutanol can be extracted by high temperature through the headspace; while the prior art uses anhydrous ethanol, chloroform, tetrahydrofuran and other solvents to soak and extract chlorobutanol, and then takes the soaking liquid for detection, and the detection cycle is long. 3. The present invention uses ethanol aqueous solution as a solvent, and the solvent is safe and friendly to the operator, and is simple and easy to obtain. 4. Through the verification of the extraction method in 1.4 (recovery experiment), we confirmed that the extraction method of the present invention can completely extract the trichlorobutanol adsorbed by the packaging material, and thus the detection method of the present invention can detect the true mass of the adsorbed trichlorobutanol; through the methodological verification in 2.2, we confirmed the detection method of the present invention, and the detection results are true and accurate.

[0037] The following is a more detailed introduction to the method for detecting the content of chlorobutanol in the packaging material provided by the present invention.

[0038] 1. Extraction

[0039] 1.1 Sample preparation

[0040] Place the sample containing the volatile component chlorobutanol (packaging material to be tested) in a headspace bottle, and at a certain temperature, make the distribution of the volatile component chlorobutanol in the sample in the gas-liquid or gas-solid two-phase or even gas-liquid-solid three-phase reach equilibrium, and then take the gas at the top of the condensed phase and send it to the gas chromatograph for analysis, so that the volatile component chlorobutanol in the sample can be directly determined. The specific method is:

[0041] Take the packaging material to be tested (eye drop bottle to be tested), pour out the liquid medicine, rinse with ultrapure water and wipe dry, cut the eye drop bottle and the eye drop bottle stopper into pieces, put them into the headspace bottle, accurately transfer the solvent into the headspace bottle, and seal the headspace bottle.

[0042] 1.2 Solvent selection

[0043] This method uses gas phase-headspace to detect chlorobutanol. Since ethanol can dissolve chlorobutanol well, this method considers using ethanol as a solvent. Since the furnace temperature of the headspace is between 80℃-90℃, and the boiling point of ethanol is 78.3℃, the solvent cannot be completely ethanol to ensure that the gas in the headspace bottle will not explode due to the complete evaporation of the solvent. Therefore, the proportion of water phase in the solvent is increased to ensure the safety of the experiment.

[0044] Referring to the boiling point table of ethanol aqueous solution and ethanol water vapor-liquid equilibrium data (normal pressure) in the "Solvent Handbook", when the mass fraction of ethanol is 10%, its boiling point is 91.3°C. Therefore, the diluent selected for this experiment is 5%-10% ethanol aqueous solution, preferably 10% ethanol aqueous solution is more suitable.

[0045] Table 1 Boiling point of ethanol aqueous solution (Boiling point of ethanol aqueous solution in "Solvent Handbook")

[0046]

[0047] 1.3 Headspace parameter selection

[0048] Since this method is headspace sampling, the actual extraction process is carried out in the gas phase headspace sampling furnace. Since chlorobutanol is adsorbed in the packaging material, it is heated as high as possible to desorb it from the packaging material. The heating time of the headspace sampling furnace is usually 30-60 minutes. If it exceeds 60 minutes, the airtightness of the headspace bottle may be poor, thereby reducing the detection content; if the time is too short, it cannot ensure that the gas-liquid-solid phase reaches equilibrium. Therefore, after repeated experiments, this method selects a heating time of 50-60 minutes, preferably 60 minutes.

[0049] Taking into account the solvent of this method, the headspace temperature should not exceed 91.3℃. If the temperature is too low, it is not conducive to the decomposition of chlorobutanol in the packaging material. If the temperature is too high, it is easy to cause the liquid in the headspace bottle to boil, resulting in bottle explosion. The durability test results in 2.3.5 show that the RSD% of the results from 85℃ to 90℃ meet the requirements. For safety reasons, the headspace oven temperature is preferably 85℃.

[0050] 1.4 Validation of extraction method (recovery rate experiment)

[0051] 1.4.1 Extraction of Chlorobutanol Adsorbed on Polypropylene Packaging

[0052] In order to prove that this extraction method can completely extract chlorobutanol adsorbed by polypropylene packaging materials, the following experiment was designed.

[0053] Preparation of simulated samples: Take 2.0 ml of 1 mg / ml chlorobutanol aqueous solution, put it in a blank packaging material (polypropylene medicinal eye drop bottle (capacity 10 ml)), plug it, seal it and leave it at room temperature for 22 days. When preparing the simulated sample, the detection content is 1.08 mg / ml. Take out the simulated sample after 22 days and use Agilent HP-5 (30m×0.32mm, 0.25μm) chromatographic column; the initial temperature is 60℃, maintained for 10 minutes, and then heated to 150℃ at 20℃ / min, maintained for 3 minutes, and then heated to 230℃ at 50℃ / min, maintained for 2 minutes; injection port temperature: 220℃; carrier gas is nitrogen, column flow rate: 1.5ml / min, and a hydrogen flame ionization detector (FID) is used, and the detector temperature is 250℃ to detect the solution content in the packaging material, and the content of chlorobutanol adsorbed by the packaging material is detected by this method. The recovery rate is calculated using the following formula:

[0054]

[0055] Where C0 is the concentration of chlorobutanol at time 0 of the simulated sample, mg / ml;

[0056] V 样 ——Simulated sample volume;

[0057] m 包 ——The mass of chlorobutanol adsorbed by the packaging material tested by this method, mg;

[0058] C 样 ——Chlorobutanol concentration in the simulated sample after 22 days or 7 days, mg / ml.

[0059] Table 2-1 Adsorption results of polypropylene packaging materials

[0060]

[0061] The adsorption results of polypropylene packaging materials in Table 2-1 indicate that this method can completely extract the trichlorobutanol adsorbed in the polypropylene packaging materials.

[0062] In addition, theoretically, the total mass of chlorobutanol initially loaded into the packaging material should be equal to the mass of chlorobutanol adsorbed by the packaging material and the mass of chlorobutanol in the drug solution in the packaging material. That is to say, in this recovery experiment, the chlorobutanol content of the drug solution just prepared is C1, which is C0×V 样 , pour the drug solution into the packaging material, leave it for a certain period of time, and then detect the chlorobutanol content C2 in the drug solution in the packaging material, that is, C 样 ×V 样 , and the content of chlorobutanol adsorbed in the packaging material detected by this method C3, that is, m in the formula 包, comparing C2+C3 with C1, the recovery rate is basically between 95% and 105%, which meets the recovery rate requirements. After testing and calculation, the recovery rate of chlorobutanol in polypropylene packaging materials by this detection method is basically between 97% and 100%, which further shows that this method can completely extract chlorobutanol adsorbed by polypropylene packaging materials.

[0063] 1.4.2 Extraction of Chlorobutanol Adsorbed on Polyethylene Packaging Materials

[0064] In order to prove that this extraction method can completely extract chlorobutanol adsorbed by polyethylene packaging materials, the following experiment was designed.

[0065] Simulated sample preparation: Take 4.0 ml of 1 mg / ml chlorobutanol aqueous solution, put it into a blank polyethylene packaging material with a volume of 5 ml, plug it, seal it and leave it at room temperature for 7 days. When preparing the simulated sample, the detection content is 1.071 mg / ml. Take out the simulated sample after 7 days and use Agilent HP-5 (30m×0.32mm, 0.25μm) chromatographic column; the initial temperature is 60℃, keep it for 10min, increase the temperature to 150℃ at 20℃ / min, keep it for 3min, and then increase the temperature to 230℃ at 50℃ / min, keep it for 2min; the injection port temperature is 220℃; the carrier gas is nitrogen, the column flow rate is 1.5ml / min, and a hydrogen flame ionization detector (FID) is used, the detector temperature is 250℃, and the solution content in the packaging material is detected, and the chlorobutanol content adsorbed by the packaging material is detected by this method. The recovery rate is calculated using the formula in Section 1.4.1.

[0066] Table 2-2 Adsorption results of polyethylene packaging materials

[0067]

[0068] The adsorption results of polyethylene packaging materials in Table 2-2 indicate that this method is suitable for the adsorption detection of trichlorobutanol on polyethylene packaging materials.

[0069] After testing and calculation, the recovery rate of chlorobutanol in polyethylene packaging materials by this testing method is basically between 100% and 102%, which further shows that this method can completely extract chlorobutanol adsorbed by polyethylene packaging materials.

[0070] 2. Detection

[0071] 2.1 Detection Method

[0072] The headspace-gas chromatography method was used to directly detect the content of chlorobutanol adsorbed on the packaging material.

[0073] The reagents and drugs used were: anhydrous ethanol (Fisher), ultrapure water (homemade), packaging materials were polypropylene medicinal eye drop bottles (capacity 10 ml) or low-density polyethylene medicinal eye drop bottles (capacity 10 ml), chlorobutanol (Aladdin, content 99.721%).

[0074] The instruments used were: Agilent gas chromatograph (including headspace) 8890, Sartorius 1 / 100,000 balance SECURA225D-1CN SQP.

[0075] Chromatographic conditions: Agilent HP-5 (30m×0.32mm, 0.25μm) chromatographic column; initial temperature 60℃, maintained for 10min, heated to 150℃ at 20℃ / min, maintained for 3min, then heated to 230℃ at 50℃ / min, maintained for 2min; injection port temperature: 220℃; carrier gas: nitrogen, column flow rate: 1.5ml / ml, hydrogen flame ionization detector (FID) was used, and the detector temperature was 250℃.

[0076] Injection method: headspace injection, heating box temperature 85℃; quantitative loop temperature: 100℃; transfer line temperature: 110℃; sample bottle equilibration time: 60min; injection duration: 0.5min; GC cycle time: 26min. Water and ethanol were used as solvents.

[0077] Stock solution of reference substance: Accurately weigh 10 mg of chlorobutanol reference substance, place it in a 10 ml volumetric flask, add 1 ml of ethanol to dissolve it, and then dilute to the scale with ultrapure water.

[0078] Preparation of blank packaging materials: Take blank packaging materials of the same model that have never been filled with liquid medicine, cut up the bottle body and sealing plug, and set aside. (A set of blank packaging materials consists of a bottle body and a bottle plug)

[0079] Control solution-1: Place a set of blank packaging materials into a 20ml headspace bottle, accurately pipette 1.0ml of the reference substance stock solution into it, and seal the headspace bottle. (Prepare reference substance stock solution-2 and control solution-2 in parallel)

[0080] Blank sample: Place a set of blank packaging materials into a 20 ml headspace bottle, accurately pipette 1.0 ml of 10% ethanol solution into it, and seal the headspace bottle.

[0081] Sample preparation: Take a set of samples to be tested, pour out the liquid, rinse with ultrapure water twice, gently dry, cut the bottle body and stopper into pieces, put them into a 20ml headspace bottle, accurately transfer 1.0ml of 10% ethanol solution into it, and seal the headspace bottle.

[0082] The above samples were detected by headspace-gas chromatography and the spectra were recorded.

[0083] 2.2 Methodological validation

[0084] 2.2.1 Linear

[0085] Weigh 400 mg of chlorobutanol reference substance accurately, place it in a 20 ml volumetric flask, and dilute it to the mark with ethanol, i.e., linear 5 solution, 20.0 mg / ml. Accurately pipette 0.5 ml, 1.0 ml, 2.5 ml, and 5.0 ml of linear 5 solution, place them in different 10 ml volumetric flasks, dilute them to the mark with ethanol, and use them as linear 1 to 4 solutions, with concentrations of 1.0 mg / ml, 2.0 mg / ml, 5.0 mg / ml, and 10.0 mg / ml, respectively.

[0086] Accurately pipette 0.1 ml of each linear solution 1 to 5 and place them in 20 ml headspace bottles containing a set of blank packaging materials, add 0.9 ml of ultrapure water, and seal the headspace bottles to serve as linear samples 1 to 5.

[0087] 2.2.2 Repeatability

[0088] Preparation of simulated samples: Take 2.0 ml of 1 mg / ml chlorobutanol aqueous solution, put it into a blank packaging material, insert a stopper, seal it and place it at room temperature for 22 days.

[0089] Preparation of reference solution: Accurately weigh 100 mg of chlorobutanol reference substance, place it in a 10 ml volumetric flask, add ethanol to dissolve it and dilute it to the mark, i.e. 10 mg / ml. Accurately pipette 0.1 ml of the solution into a 20 ml headspace bottle containing a set of blank packaging materials, add 0.9 ml of ultrapure water, and seal the headspace bottle.

[0090] Repeatability sample preparation: Take a set of simulated samples, pour out the liquid, rinse with ultrapure water twice, gently dry, cut the bottle body and stopper into pieces, put them into a 20ml headspace bottle, accurately pipette 1.0ml of 10% ethanol solution into it, and cap the headspace bottle. Prepare 6 copies in parallel as repeatability samples 1 to 6.

[0091] 2.2.3 Accuracy

[0092] For the preparation of reference solution, see 2.2.2 Repeatability.

[0093] Weigh 400 mg of chlorobutanol reference substance accurately, place it in a 20 ml volumetric flask, dilute to scale with ethanol, accurately pipette 2.5 ml, 5.0 ml, and 7.5 ml of the solution, place them in different 10 ml volumetric flasks, dilute to scale with ethanol, and use them as 50% accuracy control solution, 100% accuracy control solution, and 150% accuracy control solution, with concentrations of 5.0 mg / ml, 10.0 mg / ml, and 15.0 mg / ml, respectively. Take 1 set of simulated samples (see 2.2.2 Repeatability), pour out the liquid, rinse with ultrapure water twice, wipe dry gently, cut the bottle body and cork into pieces, place them in a 20 ml headspace bottle, accurately pipette 0.9 ml of ultrapure water into it, and then accurately pipette 0.1 ml of accuracy control solution, and cap the headspace bottle. Each concentration was prepared in triplicate and named 50%-1, 50%-2, 50%-3, 100%-1, 100%-2, 100%-3, 150%-1, 150%-2, 150%-3, respectively.

[0094] 2.2.4 Precision

[0095] Weigh 100 mg of chlorobutanol reference substance accurately, place it in a 10 ml volumetric flask, add ethanol to dissolve it and dilute to the mark, i.e. 10 mg / ml. Accurately pipette 0.1 ml of the solution into a 20 ml headspace bottle containing a set of blank packaging materials, add 0.9 ml of ultrapure water, and cap the headspace bottle. Prepare 6 copies in parallel as precision samples 1 to 6.

[0096] 2.2.5 Durability

[0097] For the preparation of reference solution, see 2.2.2 Repeatability.

[0098] Take a set of simulated samples (see 2.2.2 Repeatability), pour out the liquid, rinse with ultrapure water twice, gently dry, cut the bottle body and stopper into pieces, put them into a 20ml headspace bottle, accurately pipette 1.0ml of 10% ethanol solution into it, and seal the headspace bottle. Test the sample in a heating box at 85℃ and 90℃ respectively, and compare the results.

[0099] 2.3 Methodological Validation Results

[0100] 2.3.1 Linear Results

[0101] Table 3 Concentration and area of ​​chlorobutanol in linear samples

[0102]

[0103] See Table 3 and Figure 1 ,The results show that the linear correlation coefficient r = 0.995, and the linearity of this method is good.

[0104] 2.3.2 Repeatability results

[0105] Table 4 Repeatability sample area and measured values

[0106]

[0107] See Table 4. Figure 2 and Figure 3 The results showed that the RSD% of the 6 repeatable samples was no more than 10.0%, indicating that the repeatability of this method was good.

[0108] 2.3.3 Accuracy Results

[0109] Table 5 Accuracy of each sample area and measured value

[0110]

[0111]

[0112] As shown in Table 5, the results show that the RSD% of the 9 accuracy samples is no more than 10.0%, and the accuracy of this method is good.

[0113] 2.3.4 Precision results

[0114] Table 6 Precision of each sample area

[0115]

[0116] As shown in Table 6, the results show that the RSD% of the 6 precision samples is no more than 10.0%, and the precision of this method is good.

[0117] 2.3.5 Durability Results

[0118] Table 7 Comparison of temperature measurements of different heating boxes

[0119]

[0120] As shown in Table 7, the results show that the RSD% of the six durability samples is no more than 10.0%, and the method has good durability.

[0121] In summary, the method for detecting the content of chlorobutanol in the packaging material provided in this application does not require immersion, which solves the problem of long detection cycle. In addition, in this application, the solvent is an ethanol aqueous solution with a mass fraction of 5% to 10%, which is more safe than other solvents; the detector used is FID, which has a more stable signal, lower detection cost, and is more operator-friendly than other methods. The detection method of this application has been verified by systematic methodology, indicating that the test results are true and accurate.

[0122] It is easy for those skilled in the art to understand that, under the premise of no conflict, the above-mentioned advantageous methods can be freely combined and superimposed. The above are only preferred embodiments of the present application and are not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the present application. The above are only preferred implementation methods of the present application. It should be pointed out that for ordinary technicians in this technical field, several improvements and variations can be made without departing from the technical principles of the present application, and these improvements and variations should also be regarded as the protection scope of the present application.

Claims

1. A method for detecting the content of chlorobutanol in a packaging material, characterized in that: include: Sample preparation: Cut the packaging material to be tested into pieces and put them into a headspace bottle, add a solvent into the headspace bottle, and then cap the headspace bottle, without soaking the packaging material to be tested for a certain period of time; Headspace-gas chromatography detection: The gas in the headspace bottle is detected by headspace-gas chromatography to obtain the content of chlorobutanol in the packaging material to be tested.

2. The method for detecting the content of chlorobutanol in packaging materials according to claim 1, characterized in that: The solvent is an ethanol aqueous solution with a mass fraction of 5% to 10%.

3. The method for detecting the content of chlorobutanol in packaging materials according to claim 2, characterized in that: In the headspace-gas chromatography method, the headspace conditions are: heating temperature 85°C to 90°C, equilibration time 50min to 60min; quantitative loop temperature 98°C to 102°C, and transfer line temperature 105°C to 115°C.

4. The method for detecting the content of chlorobutanol in packaging materials according to claim 3, characterized in that: When the detection method extracts chlorobutanol from the packaging material to be tested, the extraction error is less than 5%.

5. The method for detecting the content of chlorobutanol in packaging materials according to claim 1, characterized in that: In the headspace-gas chromatography method, the injection port temperature of the gas chromatograph is 210°C to 230°C.

6. The method for detecting the content of chlorobutanol in packaging materials according to claim 1, characterized in that: In the headspace-gas chromatography method, the chromatographic column of the gas chromatography is: (5%-phenyl)-methylpolysiloxane capillary column, with a length of 30m×inner diameter of 0.32mm, a film thickness of 0.25μm, and a flow rate of 1.5mL / min.

7. The method for detecting the content of chlorobutanol in packaging materials according to claim 6, characterized in that: In the headspace-gas chromatography method, the temperature rising program of the chromatographic column is: initial temperature 55°C-65°C, maintained for 8min-12min, then increased to 140°C-160°C at 18°C / min-22°C / min, maintained for 2min-4min, then increased to 220°C-240°C at 45°C / min-55°C / min, maintained for 2min-4min.

8. The method for detecting the content of chlorobutanol in packaging materials according to claim 1, characterized in that: In the headspace-gas chromatography method, the detector of the gas chromatography is a hydrogen flame ionization detector, and the temperature of the detector is 245°C to 255°C.

9. The method for detecting the content of chlorobutanol in packaging materials according to claim 1, characterized in that: In the headspace-gas chromatography method, the carrier gas is nitrogen, the headspace injection duration is 28s to 32s, and the gas chromatography cycle time is 25min to 27min.

10. The method for detecting the content of chlorobutanol in packaging materials according to claim 1, characterized in that: The packaging material is a polypropylene medicinal eye drop bottle or a polyethylene medicinal eye drop bottle.

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