Detection method and quality control method of thymol content in triamcinolone acetonide-neomycin plaster

Abstract

The invention discloses a method for detecting the thymol content of a triamcinolone acetonide-neomycin patch and a method for quality control. The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch comprises: (1) removing the cover lining of the triamcinolone acetonide-neomycin patch and cutting it into pieces, accurately weighing the preset amount, placing it in a volumetric flask, adding an organic solvent, and shaking to dissolve the sample to be tested; (2) continuing to add anhydrous ethanol, shaking while adding to slowly precipitate out the precipitate; (3) continuing to add the same organic solvent as step (1) to the volume of the volumetric flask; (4) centrifuging, taking the supernatant; (5) using a gas chromatograph to detect the supernatant obtained in step (4). The present invention uses an organic solvent to dissolve the paste and anhydrous ethanol to precipitate rubber to extract thymol from the triamcinolone acetonide-neomycin patch, and uses gas chromatography to accurately and accurately measure the content of thymol in the extract, which is simple and easy to implement, has high precision, and good reproducibility, and provides a new indicator for the quality control of the triamcinolone acetonide-neomycin patch.

Description

Technical Field

[0001] The invention belongs to the technical field of quality detection, and particularly relates to a thymol content detection method and a quality control method of a triamcinolone acetonide-neomycin patch. Background Art

[0002] Thymol, also known as thymol, is a common disinfectant and preservative. It exists in the volatile oil of plants such as thyme, and can also be synthesized from raw materials such as para-cymene, citronellal, or meta-cresol. Thymol has a stronger bactericidal effect than phenol and is less toxic. It has antibacterial, antifungal, insecticidal, and antioxidant effects. It is used as a preservative, bactericide, liver function reagent, etc. in medicine. In China, the drugs containing thymol are mainly compound preparations, including triamcinolone acetonide neomycin plaster, mint thymol ointment, etc.

[0003] Triamcinolone acetonide-neomycin patch is a compound preparation. It is a rubber paste made of triamcinolone acetonide acetate, neomycin sulfate, thymol and other excipients with natural rubber and other matrices. It was developed by Shanghai Sanitary Materials Factory in 1979. It is mainly used for localized neurodermatitis and chronic eczema, and can also be used for small areas of psoriasis. It can be seen that thymol plays a very important role in triamcinolone acetonide-neomycin patch.

[0004] The quality control of triamcinolone acetonide-neomycin plaster currently follows the National Drug Standard WS-10001-(HD-1079)-2002-2006 of the State Food and Drug Administration. This standard mainly implements the identification of the quality of triamcinolone acetonide-neomycin plaster from the following three aspects: (1) Take one tablet of this product, sprinkle about 50 mg of calcium oxide on the plaster surface, break it into small pieces, place it in a crucible and burn it until it is carbonized, cool it, add about 1 ml of nitric acid, boil it, and cool it; take another clean and dry test tube, add about 1 ml of 1% potassium dichromate sulfuric acid solution, rotate the test tube, so that the solution is evenly applied to the tube wall, then transfer the above solution into the test tube, slightly heat and rotate the test tube, the solution should no longer be evenly applied to the tube wall, and there should be oil-like dirt on the tube wall. (2) Take 15 tablets of this product and add 60 ml of ether to soak them twice, 40 ml for the first time and 20 ml for the second time, so that the matrix is ​​dissolved. The soaked solution is combined into a separatory funnel. The remaining cloth is soaked with 12 ml of water again. The soaked water is poured into the above solution and shaken gently. The water layer is separated and concentrated to about 1 ml as the test solution. Separately, take a neomycin standard and add water to make a solution containing 20 mg per 1 ml as the standard solution. According to the thin layer chromatography method (Appendix VB of Part II of the Chinese Pharmacopoeia 2000 Edition), 3 ml of each of the above two solutions are taken and applied to the same On a silica gel H thin layer plate (1.5 g silica gel H was slurried with 6 ml 0.25% sodium carboxymethyl cellulose solution to prepare the plate), methanol-ethyl acetate-acetone-8.8% ammonium acetate solution (25:15:10:40) was used as the developing agent. After development, it was air-dried and dried at 110°C for 20 minutes. While hot, it was sprayed with 10% sodium hypochlorite solution. The thin layer plate was cooled in a ventilated place for a while, and then sprayed with potassium iodide starch solution (0.5 g potassium iodide in 100 ml of 0.5% starch solution). Immediately check: the color and position of the main spot of the test solution should be the same as the main spot of the standard. (3) Take the above aqueous solution and develop the identification reaction of sulfate (Appendix III of Part II of the Chinese Pharmacopoeia 2000).

[0005] It can be seen that the current standard mainly identifies the liquid properties of the extract, and qualitatively identifies triamcinolone acetonide acetate and neomycin sulfate in the extract. However, triamcinolone acetonide-neomycin patch contains three active ingredients, but the current standard does not test the content of thymol, resulting in incomplete quality control of triamcinolone acetonide-neomycin patch; at the same time, the extraction of active ingredients in rubber plasters in the prior art mostly adopts reflux extraction and extraction methods, but reflux extraction and extraction methods are relatively cumbersome and complicated, and the extraction effect is not always good. Summary of the invention

[0006] The invention aims to provide a method for detecting the thymol content of a triamcinolone acetonide-neomycin patch and a method for quality control. The method is simple and easy to implement, has high precision and good reproducibility, and provides a new indicator for the quality control of the triamcinolone acetonide-neomycin patch.

[0007] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0008] A method for detecting the thymol content of triamcinolone acetonide-neomycin plaster, the method comprising the following steps:

[0009] (1) Remove the cover liner of the triamcinolone acetonide-neomycin patch and cut it into pieces. After accurately weighing a preset amount, place it in a volumetric flask, add an organic solvent, and shake or sonicate to dissolve the test product;

[0010] (2) Continue to add anhydrous ethanol, shaking while adding to allow the precipitate to slowly separate out;

[0011] (3) Continue to add the same organic solvent as in step (1) to the volume of the volumetric flask;

[0012] (4) Centrifugation and taking the supernatant;

[0013] (5) Using a gas chromatograph to detect the supernatant obtained in step (4).

[0014] The invention adopts a method of dissolving a paste with an organic solvent and precipitating rubber with anhydrous ethanol, so as to effectively and simply extract thymol, an active ingredient, from the triamcinolone acetonide-neomycin patch, and accurately and precisely measures the content of thymol in the extract by gas chromatography, thereby establishing a strict standard for controlling the quality of the triamcinolone acetonide-neomycin patch, being helpful for quality control of the triamcinolone acetonide-neomycin patch and optimizing the market of the triamcinolone acetonide-neomycin patch.

[0015] Preferably, in step (1) of the above-mentioned method for detecting the thymol content of the triamcinolone acetonide-neomycin patch, the organic solvent comprises at least one of chloroform, n-heptane, n-hexane and ether. According to tests, the above four organic solvents can dissolve the paste and extract thymol.

[0016] Preferably, in the above-mentioned method for detecting the thymol content of the triamcinolone acetonide-neomycin patch, in steps (1) and (2), the shaking or ultrasound required time is 25-35 minutes. Under the shaking or ultrasound time, the paste and thymol can be completely dissolved.

[0017] Preferably, in the above-mentioned method for detecting the thymol content of triamcinolone acetonide-neomycin patch, the volume ratio of the organic solvent to anhydrous ethanol is (1.5-7):1.

[0018] Preferably, in step (4) of the above-mentioned method for detecting the thymol content of triamcinolone acetonide-neomycin patch, centrifugation is performed at 10,000 r / min for 5 min.

[0019] Preferably, the method for detecting the thymol content of the above-mentioned triamcinolone acetonide-neomycin patch comprises the following steps:

[0020] (1) Remove the cover liner of the triamcinolone acetonide-neomycin patch and cut it into pieces. After accurately weighing the amount of one patch, place it in a 50 mL volumetric flask, add 25-35 mL of n-heptane, and shake or sonicate for 25-35 minutes to dissolve the test product;

[0021] (2) Continue to add 5-15 ml of anhydrous ethanol, shaking while adding to allow the precipitate to slowly precipitate;

[0022] (3) Continue to add n-heptane to the volume of the volumetric flask and shake well;

[0023] (4) Centrifuge at 10,000 rpm for 5 min and collect the supernatant;

[0024] (5) Using a gas chromatograph to detect the supernatant obtained in step (4).

[0025] Wherein, the gas chromatography conditions used in step (5) are:

[0026] Chromatographic column: a capillary column filled with (5%-phenyl)-methyl polysiloxane;

[0027] Carrier gas: nitrogen;

[0028] Column flow rate: 2.0 mL / min;

[0029] Split ratio: 5:1;

[0030] Injection volume: 1 μl;

[0031] Inlet temperature: 200°C;

[0032] Detector: Hydrogen flame ionization detector, operating temperature is 300℃;

[0033] Column temperature: ① Maintain at 70℃ for 2 min; ② Increase the temperature to 200℃ at 10-20℃ / min and maintain at 200℃ for 2 min; ③ Increase the temperature to 240℃ at 15-30℃ / min and maintain at 240℃ for 5 min.

[0034] Under the chromatographic conditions, the detection limit of the method of the present invention for thymol is 0.4416 μg / ml, the quantitative limit is 1.104 μg / ml, the detection sensitivity is high, the accuracy is high, and the reproducibility is good; during the detection process, the column temperature gradually increases, which can ensure that the target compound and impurities are fully separated.

[0035] As a further preference, the column temperature during detection is:

[0036] ① Maintain at 70℃ for 2min;

[0037] ② Raise the temperature to 200℃ at 15℃ / min and maintain at 200℃ for 2min;

[0038] ③ Raise the temperature to 240℃ at 20℃ / min and maintain at 240℃ for 5min.

[0039] The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch of the present invention further comprises the step of preparing a reference solution, which comprises: dissolving thymol with n-heptane to obtain a reference mother solution with a concentration of 2 mg / mL; and gradiently diluting the reference mother solution with a mixed solvent of n-heptane: anhydrous ethanol in a volume ratio of 42:8 to obtain a series of reference solutions.

[0040] The present invention also provides a quality control method for triamcinolone acetonide-neomycin patch, which comprises the step of detecting the thymol content in the triamcinolone acetonide-neomycin patch by the method of the present invention, and taking the measured thymol content as a quality control index; of course, it can also be used in combination with other indexes.

[0041] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0042] (1) The present invention adopts a method of dissolving the paste with an organic solvent and precipitating the rubber with anhydrous ethanol to effectively and simply extract the active ingredient thymol from the triamcinolone acetonide-neomycin patch, and uses gas chromatography to accurately and precisely measure the content of thymol in the extract, thereby establishing strict standards for controlling the quality of the triamcinolone acetonide-neomycin patch, which is helpful for quality control of the triamcinolone acetonide-neomycin patch and optimizing the market of the triamcinolone acetonide-neomycin patch.

[0043] (2) The present invention sets gas chromatography conditions specifically for thymol. Under the chromatographic conditions, the detection limit of the method of the present invention for thymol is 0.4416 μg / ml, and the quantitative limit is 1.104 μg / ml. The detection sensitivity, accuracy and reproducibility are high. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 A spectrum obtained by gas chromatography detection of an extraction solvent using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention;

[0045] Wherein, min represents retention time (minutes), pA is the current unit; the same below;

[0046] Figure 2 A spectrum obtained by gas chromatography detection of a reference substance using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention;

[0047] Figure 3A spectrum obtained by gas chromatography detection of the triamcinolone acetonide-neomycin patch produced by Enterprise A using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention;

[0048] Figure 4 A spectrum obtained by gas chromatography detection of the triamcinolone acetonide-neomycin patch produced by Enterprise B using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention;

[0049] Figure 5 A spectrum obtained by gas chromatography detection of the triamcinolone acetonide-neomycin patch produced by Enterprise C using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention;

[0050] Figure 6 A spectrum obtained by gas chromatography detection of the triamcinolone acetonide-neomycin patch produced by Enterprise D using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention;

[0051] Figure 7 A spectrum obtained by gas chromatography detection of the triamcinolone acetonide-neomycin patch produced by Enterprise E using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention;

[0052] Figure 8 The invention discloses a standard curve obtained by gas chromatography detection of a reference substance using the thymol content detection method of the triamcinolone acetonide-neomycin patch of the present invention. DETAILED DESCRIPTION

[0053] The technical solution of the present invention is further described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0054] Example 1

[0055] The present embodiment provides a method for detecting the thymol content of triamcinolone acetonide-neomycin plaster, the method comprising the following steps:

[0056] 1. Preparation of test solution

[0057] The specific steps include:

[0058] (1) Take ten pieces of the triamcinolone acetonide-neomycin patch to be tested, accurately weigh them, cut them into pieces, accurately weigh the amount of one piece of patch, put them into a 50 mL volumetric flask, add 25 mL of heptane, and shake them for 30 minutes using a KS4000icontrol constant temperature oscillator to dissolve the paste;

[0059] (2) Continue to add 8 mL of anhydrous ethanol, shaking while adding to allow the precipitate to slowly precipitate;

[0060] (3) Continue to add heptane to dilute to scale and shake well;

[0061] (4) Centrifuge at 10,000 r / min for 5 min and collect the supernatant to obtain the test solution.

[0062] 2. Preparation of reference solution

[0063] Dissolve thymol (China Inspection and Quarantine Institute, 100963-202004, content: 99.9%) in heptane to obtain a reference substance mother solution with a concentration of 2 mg / mL; use a heptane: anhydrous ethanol mixed solvent with a volume ratio of 42:8 to gradiently dilute the reference substance mother solution to obtain a series of reference substance solutions with concentrations of 11.04, 22.08, 44.16, 66.23, 88.31, and 110.39 μg / ml.

[0064] 3. Gas chromatography detection

[0065] (1) Gas chromatography detection

[0066] Take 20 μl of each of the solvent, reference solution and test solution, and use Agilent 7890B gas chromatograph for detection. The gas chromatography conditions are as follows:

[0067] Chromatographic column: Agilent DB-5, 30m×0.32mm×0.25μm;

[0068] Carrier gas: nitrogen;

[0069] Column flow rate: 2.0 mL / min, constant flow;

[0070] Split ratio: 5:1;

[0071] Injection volume: 1 μl;

[0072] Injection method: direct injection;

[0073] Inlet temperature: 200°C;

[0074] Detector: Hydrogen flame ionization detector (FID), operating temperature is 300°C;

[0075] Column temperature: ① Maintain at 70℃ for 2 min; ② Increase the temperature to 200℃ at 15℃ / min and maintain at 200℃ for 2 min; ③ Increase the temperature to 240℃ at 20℃ / min and maintain at 240℃ for 5 min.

[0076] The chromatographic analysis results of the solvent are as follows Figure 1 The chromatographic analysis results of the reference solution are shown in Figure 2 The chromatographic analysis results of the five test solutions are shown in Figure 3 , Figure 4 , Figure 5 , Figure 6 and Figure 7 shown.

[0077] Depend on Figures 1 to 7 As shown, the main peak - thymol in the chromatogram is clear, and the solvent and blank excipients will not interfere with the detection of thymol, and the specificity is good.

[0078] (2) Standard curve drawing

[0079] Take 20 μl of each series of reference solution, use the above gas chromatography conditions for detection, and use the concentration (μg / ml) as the horizontal axis and the corresponding peak area as the vertical axis for linear regression. The linear relationship is shown in Table 1 and the standard curve is shown in Figure 8 shown.

[0080] Table 1 Linear relationship of thymol standard

[0081] serial number Concentration (μg / ml) Peak area 1 11.04 37.38994 2 22.08 74.42765 3 44.16 151.13845 4 66.23 226.78944 5 88.31 304.62776 6 110.39 378.32447

[0082] like Figure 8 As shown, the regression equation is y = 3.4441x-0.9854, R 2 =1, the results showed that thymol had a good linear relationship in the range of 11.04-110.39 μg / ml.

[0083] (3) Quantification limit and detection limit testing

[0084] Accurately measure 1 ml of 11.04 μg / ml standard solution and place it in 10 ml and 25 ml volumetric flasks respectively, add chloroform: anhydrous ethanol mixed solvent with a volume ratio of 35:15 to dilute to the scale, shake well, and inject for determination. The S / N ratios are 19.6 and 7.5 respectively. According to calculation, the quantitative limit concentration of thymol detected by the detection method of the present invention is 1.104 μg / ml, and the detection limit concentration is 0.4416 μg / ml.

[0085] (4) Method accuracy test

[0086] Take half a tablet of triamcinolone acetonide-neomycin plaster, accurately weigh 6 portions, accurately add 0.75 ml of thymol reference substance mother solution to each portion, and then prepare the test solution according to the same method as "1. Preparation of test solution", and detect it according to the same method as "(1) Gas chromatography detection", and calculate the recovery of thymol. The calculation results are shown in Table 2.

[0087] Table 2 Spiked recovery test

[0088]

[0089] As can be seen from Table 2, the average recovery rate of thymol reached 98.91%, and the RSD was 0.9%, indicating that the method of the present invention has high accuracy.

[0090] (5) Repeatability test

[0091] The same triamcinolone acetonide-neomycin patch was divided into six portions, and then the test solution was prepared according to the same method as “1. Preparation of test solution”, and the test was performed according to the same method as “(1) Gas chromatography detection”. The content of thymol in the test solution was calculated. The results are shown in Table 3.

[0092] Table 3 Repeatability test results

[0093]

[0094] As can be seen from Table 3, the same triamcinolone acetonide-neomycin patch was subjected to a repeatability parallel test, and it was found that the RSD of the test results was 2.5%, indicating that the method of the present invention has good repeatability.

[0095] (6) Test solution stability test

[0096] Take the test solution No. 1 prepared under the above "Repeatability Test" and perform gas chromatography detection after 0 hours, 8 hours, 24 hours, and 48 hours respectively. The test results are shown in Table 4. Table 4 Test solution stability test results

[0097]

[0098] As can be seen from Table 4, after being placed for 48 hours, the peak area of ​​the test solution is still equivalent to that when it was just prepared, and the RSD is 3.0%, indicating that the test solution prepared by the method of the present invention has good stability and can maintain good stability within 48 hours, and even better within 24 hours.

[0099] (7) Sample measurement

[0100] A total of 20 batches of triamcinolone acetonide-neomycin patches produced by five companies were obtained, and then the test solutions were prepared according to the same method as “1. Preparation of test solution”. The solutions were tested according to the same method as “(1) Gas chromatography detection”, and the content of thymol therein was calculated. The test results are shown in Table 5.

[0101] Table 5 Thymol content in samples from different manufacturers

[0102] Production Company Production batch number <![CDATA[Content (μg / cm 2 )]]> A 210607 119.3 A 210901 117.0 A 220101 106.1 A 220303 126.8 A 220304 117.1 B 210601 79.5 B 210701 96.3 C 210505 120.1 D 20210105 120.3 E 200914 108.1 E 200916 117.1 E 210503 109.7 E 210608 108.1 E 210705 109.4 E 210715 106.2 E 210826 107.2 E 211001 104.4 E 211201 104.0 E 220102 114.7 E 220107 112.7

[0103] The thymol content of triamcinolone acetonide-neomycin patches of various companies was statistically analyzed, and the statistical results are shown in Table 6.

[0104] Table 6 Thymol content range in samples from different manufacturers

[0105] Manufacturer Batch number <![CDATA[Thymol content (μg / cm 2 )]]> Company A 5 106.1～126.8 Company B 2 79.5～96.3 Company C 1 120.1 Company D 1 120.3 Enterprise E 11 104.0～117.1

[0106] As can be seen from Table 6, there are certain differences in the thymol content in triamcinolone acetonide-neomycin patches produced by different manufacturers. The thymol content in the samples of companies C and D is the highest, and the samples of company A also have products with high thymol content. The thymol content in the samples of company B is the lowest.

[0107] Based on the analysis of the above experimental results, it can be seen that there are certain differences in the content of thymol, the active ingredient, in triamcinolone acetonide-neomycin patches from different manufacturers and batches. The determination item of thymol content should be added to the quality standard of triamcinolone acetonide-neomycin patches to increase the controllability of drug quality.

[0108] The thymol content detection method of the present invention was verified, and the results are shown in Table 7.

[0109] Table 7 Verification conclusion of the method of the present invention

[0110]

[0111] According to the statistics in Table 7, the thymol content detection method of the present invention meets the verification requirements of the United States Pharmacopoeia and the Chinese Pharmacopoeia, indicating that it can be used as a detection method for the thymol content in the quality standard of triamcinolone acetonide-neomycin patch.

[0112] Example 2

[0113] The present embodiment is a method for detecting the thymol content of a triamcinolone acetonide neomycin patch, which is substantially the same as that of Example 1, except that: the organic solvents used in step (1) are n-heptane, n-hexane, and ether; and the amounts of each organic solvent (n-heptane, n-hexane, ether, and chloroform) are set to 20 mL, 25 mL, 30 mL, and 35 mL, respectively. The test results of the thymol content in the triamcinolone acetonide neomycin patch under different organic solvents and different organic amounts are shown in Table 8.

[0114] Table 8 Effect of organic solvent type and dosage on thymol extraction

[0115]

[0116] It can be seen from Table 8 that when the volume of these four organic solvents is greater than 20 ml, they can all dissolve the paste and extract thymol.

[0117] Example 3

[0118] The present embodiment provides a method for detecting the thymol content of a triamcinolone acetonide-neomycin patch. The method is basically the same as that of Example 1, except that: 25 mL of chloroform or n-heptane is used in step (1), and the amount of anhydrous ethanol used in step (2) is set to 1 ml, 3 ml, 5 ml, 8 ml, 10 ml, 13 ml, 15 ml, and 20 ml, respectively; the extraction effect of thymol is shown in Table 9.

[0119] Table 9 Effect of different anhydrous ethanol dosage on thymol extraction effect

[0120]

[0121] It can be seen from Table 9 that when n-heptane is used as the extraction solvent and the amount of anhydrous ethanol added is less than 5 ml, the precipitation is not obvious. When the amount of anhydrous ethanol added is greater than 13 ml, the rubber precipitates too quickly, resulting in a low thymol content and poor extraction effect. That is, when n-heptane is used as the extraction solvent, the amount of anhydrous ethanol added is preferably between 5 and 13 ml. When chloroform is used as the extraction solvent and the amount of anhydrous ethanol added is less than 5 ml, the precipitation is not obvious, but different amounts of anhydrous ethanol added can effectively extract thymol.

[0122] Example 4

[0123] This embodiment provides a method for detecting the thymol content of triamcinolone acetonide-neomycin patch. The method is basically the same as that of Example 1, except that: in step (1), ultrasonic extraction is used instead of shaking extraction. The extraction effect of thymol is shown in Table 10.

[0124] Table 10 Extraction effect of thymol under ultrasonic mode

[0125]

[0126] As can be seen from Table 10, both shaking and ultrasonic methods can effectively extract thymol.

Claims

1. A method for detecting the thymol content of triamcinolone acetonide-neomycin plaster, characterized in that: The following steps are involved: (1) Remove the cover liner of the triamcinolone acetonide-neomycin patch and cut it into pieces. After accurately weighing the preset amount, place it in a volumetric flask, add an organic solvent, and shake or sonicate to dissolve the test product; (2) Continue to add anhydrous ethanol, shaking while adding to allow the precipitate to slowly precipitate; (3) Continue to add the same organic solvent as in step (1) to make up to the mark on the volumetric flask; (4) Centrifuge and take the supernatant; (5) using a gas chromatograph to detect the supernatant obtained in step (4); In step (1), the organic solvent comprises at least one of chloroform, n-heptane, n-hexane and diethyl ether; The gas chromatography conditions used in step (5) are: Chromatographic column: Capillary column filled with (5%-phenyl)-methyl polysiloxane; Carrier gas: nitrogen; Column flow rate: 2.0 mL / min; Split ratio: 5:1; Injection volume: 1 μl; Inlet temperature: 200°C; Detector: Hydrogen flame ionization detector, operating temperature is 300℃; Column temperature: ① Maintain at 70℃ for 2 min; ② Increase the temperature to 200℃ at 10-20℃ / min and maintain at 200℃ for 2 min; ③ Increase the temperature to 240℃ at 15-30℃ / min and maintain at 240℃ for 5 min.

2. The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch according to claim 1, characterized in that: In steps (1) and (2), the shaking or ultrasonication time is 25-35 min.

3. The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch according to claim 1, wherein: The volume ratio of organic solvent to anhydrous ethanol is (1.5-7):

1.

4. The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch according to claim 1, characterized in that: In step (4), centrifuge at 10,000 r / min for 10 min.

5. The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch according to claim 1, characterized in that: The following steps are involved: (1) Remove the cover liner of the triamcinolone acetonide-neomycin patch and cut it into pieces. After accurately weighing the amount of one patch, place it in a 50 mL volumetric flask, add 25-35 mL of n-heptane, and shake or sonicate for 25-35 min to dissolve the test product; (2) Continue to add 5-15 ml of anhydrous ethanol, shaking while adding to allow the precipitate to slowly precipitate; (3) Continue to add n-heptane to the volumetric flask mark and shake well; (4) Centrifuge at 10,000 r / min for 5 min and collect the supernatant; (5) The supernatant obtained in step (4) is detected by gas chromatography.

6. The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch according to claim 1, characterized in that: The column temperature during detection is: ① Maintain at 70℃ for 2min; ② Raise the temperature to 200℃ at 15℃ / min and maintain at 200℃ for 2 min; ③ Raise the temperature to 240℃ at 20℃ / min and maintain at 240℃ for 5 min.

7. The method for detecting the thymol content of the triamcinolone acetonide-neomycin patch according to claim 1, characterized in that: The method also includes the step of preparing a reference solution, which includes: dissolving thymol with n-heptane to obtain a reference mother solution with a concentration of about 2 mg / mL; and gradiently diluting the reference mother solution with a mixed solvent of n-heptane: anhydrous ethanol in a volume ratio of 42:8 to obtain a series of reference solutions.

8. A quality control method for triamcinolone acetonide-neomycin plaster, characterized in that: The method comprises the step of detecting the content of thymol in the triamcinolone acetonide-neomycin patch by using the method described in any one of claims 1 to 7.

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