Method for detecting content of ethylparaben in dimeticone emulsion

Abstract

The invention provides a method for detecting ethylparaben in dimeticone emulsion, and belongs to the field of medicine analysis and detection. The detection method comprises the following steps: carrying out ultrasonic demulsification on a dimeticone emulsion sample by using an organic solvent, and centrifuging to obtain supernate; diluting the supernate with an acetonitrile solution to obtain a test solution; and finally, injecting the test solution into a liquid chromatograph for detection. According to the present invention, the organic solvent ultrasonic demulsification method is adopted to make the demulsification of the sample stable, the acetonitrile is adopted as the dilution solvent to ensure the good peak pattern of ethylparaben, the method has advantages of accurate determination result, good reproducibility and the like, the adopted solvent is relatively environmentally friendly, and the verification results of the method show that the method has the broad application prospect. The content determination of ethylparaben in the dimeticone emulsion can be met.

Description

Technical Field

[0001] The invention relates to the technical field of drug analysis and detection, and in particular to a method for detecting the content of ethylparaben in a dimethicone emulsion. Background Art

[0002] Simethicone emulsion is an oral emulsion for defoaming. The active ingredient is dimethicone. It is used to improve abdominal symptoms caused by gas in the gastrointestinal tract; to remove bubbling mucus in the stomach during gastroscopy; and to remove gas in the intestine during X-ray examination of the abdomen. Simethicone emulsion is a white emulsion with a fragrant smell.

[0003] Simethicone emulsion is used as an auxiliary drug for gastroscopy and radiology. The surface tension of the dimethicone in it is small, which can change the surface tension of bubbles and make them burst, thus eliminating the bubbles in the gastrointestinal tract and allowing the gas retained by the bubbles to be discharged, thereby relieving flatulence. At the same time, it can also eliminate bubbly mucus in the stomach, thereby improving the clarity of gastroscopy and radiology.

[0004] Ethyl paraben is obtained by esterification of p-hydroxybenzoic acid and ethanol. It belongs to the ester class and is commonly used as an antibacterial preservative in food, medicine and cosmetics. As an antibacterial agent, ethyl paraben can be added to dimethicone emulsions.

[0005] However, excessive amounts of ethylparaben can cause contact dermatitis, urticaria, and angioedema. Contact with the eyes can cause irritation and pain, and contact with the lips can cause a tingling sensation.

[0006] Therefore, it is very important to determine the content of ethylparaben in dimethicone emulsion. Summary of the invention

[0007] In view of this, the present invention provides a method for detecting the content of ethylparaben in a dimethicone emulsion. The method adopts a method of adding an organic solvent and breaking the emulsion by ultrasonic machinery, does not require heating, and the pretreatment process is relatively short in time. Multiple samples can be processed simultaneously without the risk of cross contamination, and the operation is safer and more convenient. At the same time, the influence of acids, alkalis and other destructive agents on the stability of ethylparaben is also avoided.

[0008] The method for detecting ethyl hydroxybenzoate in the dimethicone emulsion of the present invention comprises the following steps:

[0009] (1) Ultrasonic demulsification: accurately weigh a sample of dimethicone emulsion, place it in a volumetric bottle, add an organic solvent and ultrasonically dissolve it, then continue to add solvent to dilute to the scale to obtain a dimethicone emulsion dilution, shake well, and centrifuge to obtain a supernatant;

[0010] (2) Dilution: Accurately measure the supernatant and place it in a volumetric flask, dilute it to the mark with acetonitrile solution, shake well to obtain an acetonitrile dilution, filter, and take the filtrate as the test solution;

[0011] (3) Detection: Inject the test solution into a liquid chromatograph for detection.

[0012] Preferably, the organic solvent in step (1) is an ethanol aqueous solution; the volume concentration of ethanol in the ethanol aqueous solution is 70-80%.

[0013] Preferably, the concentration of the dimethicone emulsion in the dimethicone emulsion diluent of step (1) is 0.095 to 0.105 g / mL.

[0014] Preferably, the centrifugal speed in step (1) is 4000-4500 rpm, and the centrifugal time is 20-25 minutes.

[0015] Preferably, the volume concentration of acetonitrile in the acetonitrile solution in step (2) is 50%.

[0016] Preferably, the concentration of the supernatant in the acetonitrile dilution in step (2) is 0.1 mL / mL.

[0017] Preferably, the chromatographic conditions of the liquid chromatography in step (3) are:

[0018] Chromatographic column: Octadecylsilane bonded silica gel is used as filler, and the column parameters are CAPCELL PAKC184.6mm×150mm, 5μm;

[0019] Mobile phase: 1% glacial acetic acid solution as mobile phase A and acetonitrile as mobile phase B for gradient elution;

[0020] Column temperature: 50°C;

[0021] Detection wavelength: 254nm;

[0022] Injection volume: 50ul.

[0023] More preferably, the gradient elution method is: 0→6 minutes, mobile phase A and mobile phase B are 50% respectively; 7→15 minutes, mobile phase A and mobile phase B are 15% and 85% respectively; 15.1→25 minutes, mobile phase A and mobile phase B are 50% respectively.

[0024] Compared with the prior art, the present invention has the following beneficial effects: the present invention provides a method for detecting the content of ethylparaben in a dimethicone emulsion, the method adopts an organic solvent ultrasonic demulsification method to make the sample demulsification stable, and at the same time adopts 50% acetonitrile as a dilution solvent to ensure that the peak shape of ethylparaben is good. The method has the advantages of accurate measurement results, good reproducibility, etc., and at the same time, the solvent adopted is relatively environmentally friendly. The method has been verified to meet the requirements for the determination of the content of ethylparaben in a dimethicone emulsion. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The characteristic spectrum of the ethylparaben reference substance in Example 1;

[0026] Figure 2 It is a linear regression graph of the ethyl paraben reference substance in Example 1 at a limit concentration of 10% to 200%;

[0027] Figure 3 This is the characteristic spectrum of the ethyl hydroxybenzoate reference substance of Comparative Example 1;

[0028] Figure 4 This is the characteristic spectrum of the comparative example 2-hydroxyethyl benzoate reference substance. DETAILED DESCRIPTION

[0029] The present invention provides a method for detecting the content of ethylparaben in a dimethicone emulsion, and adopts a high performance liquid chromatography method to calculate the content of ethylparaben. In a specific embodiment of the present invention, the reagents used are all chromatographically pure reagents available on the market, and the methods used in the present invention are conventional methods unless otherwise specified.

[0030] Some of the instruments and reagents used in the present invention are: liquid chromatograph (Shimadzu LC-20AT), centrifuge (Shanghai Anting TDC-60B), electronic balance (Mettler), methanol (chromatographically pure, Kleiman), ethanol (chromatographically pure, EMOON), acetonitrile (chromatographically pure, Fisher), and glacial acetic acid (chromatographically pure, EMOON).

[0031] The present invention will be further described below in conjunction with the embodiments.

[0032] Example 1

[0033] A method for detecting the content of ethylparaben in a dimethicone emulsion, comprising the following steps:

[0034] 1. Raw materials

[0035] Reference substance: ethylparaben (source: China Food and Drug Inspection Institute, batch number: 100847-202105);

[0036] Test sample: Dimethicone emulsion (Source: Hebei Huachen Pharmaceutical Group Co., Ltd.). The formula composition is shown in Table 1:

[0037] Table 1 Prescription composition of dimethicone emulsion

[0038] Raw materials effect Prescription (theoretical dosage) / 1ml Dimethicone Active ingredients 20mg Silicon dioxide Defoaming agent 0.5mg Polysorbate 80 Emulsifier 4.5mg Sorbitan Oleate Emulsifier 4.5mg Sodium Carboxymethyl Cellulose Thickener 15mg Anhydrous ethanol Solvents 10mg Ethylparaben Antibacterial Agents 1mg Butylated Hydroxytoluene Antioxidants 0.01mg Saccharin Sodium Flavoring agents 0.5mg Fresh milk flavor Flavoring agents 0.25mg Purified water Dispersing solvent Add to 0.9994g

[0039] 2. Chromatographic conditions

[0040] Chromatographic column: Octadecylsilane bonded silica gel as filler (CAPCELL PAK C184.6mm×150mm, 5μm)

[0041] Mobile phase: 1% acetic acid solution as mobile phase A, acetonitrile as mobile phase B, 0→6 minutes, mobile phase A and mobile phase B are 50% respectively; 7→15 minutes, mobile phase A and mobile phase B are 15% and 85% respectively; 15.1→25 minutes, balance the system;

[0042] Column temperature: 50°C;

[0043] Detection wavelength: 254nm;

[0044] Injection volume: 50ul.

[0045] 3. Sample Processing

[0046] Blank solvent: 50% acetonitrile.

[0047] Reference substance solution: accurately weigh 10.0 mg of ethylparaben reference substance, place it in a 100 ml volumetric flask, dilute to the mark with 50% acetonitrile solution, and shake well to obtain the reference substance dilution solution; accurately measure 2.0 ml of the reference substance dilution solution, place it in a 20 ml volumetric flask, dilute to the mark with 50% acetonitrile solution, and shake well to obtain the reference substance solution.

[0048] Test solution: accurately weigh 1.0 g of the test dimethicone emulsion, place it in a 10 ml volumetric flask, add 7 ml of 75% volume concentration ethanol solution, ultrasonically break the emulsion at 1000 Hz for 10 minutes, then continue to dilute to the scale with ethanol solution, shake well, centrifuge at 4000 rpm for 20 minutes, accurately measure 2.0 ml of the supernatant, place it in a 20 ml volumetric flask, dilute to the scale with 50% volume concentration acetonitrile solution, shake well, filter, and take the filtrate to obtain the test solution.

[0049] Blank excipient solution: Prepare a solution without ethylparaben according to the formula of the test dimethicone emulsion, then accurately weigh 1.0 g of the above solution, place it in a 10 ml volumetric flask, and prepare it according to the "test solution" to obtain a blank excipient solution.

[0050] 4. Experimental Procedure

[0051] (1) System suitability test

[0052] Inject the test solution and the reference solution into the liquid chromatograph respectively and record the chromatogram. The characteristic spectrum of the ethylparaben reference substance is as follows: Figure 1 The system suitability was investigated, and the test results are shown in Tables 2 and 3. The results show that the chromatographic parameters meet the requirements of the pharmacopoeia, and the test results are consistent with the theoretical values.

[0053] Table 2 Ethyl Hydroxybenzoate Methodology - System Suitability Solution Results

[0054]

[0055] Table 3 Ethyl Hydroxybenzoate Methodology - Test Solution Results

[0056]

[0057] (2) Solution stability

[0058] Take the reference solution and the test solution under the system suitability test and examine the solution stability at the corresponding time. The test results are shown in Tables 4 and 5 below.

[0059] Table 4 Ethyl Hydroxybenzoate Methodology - Solution Stability - Reference Solution Results

[0060] Time / h <![CDATA[A 羟苯乙酯 ]]> 0 2967115 17 2980911 26 2974073 42 2997901 average 2980000 RSD / % 0.45

[0061] Table 5 Ethyl Hydroxybenzoate Methodology - Solution Stability - Test Solution Results

[0062] Time / h Ethyl paraben content mg / ml 0 1.054 14 1.058 23 1.055 39 1.059 average value 1.057 RSD% 0.24

[0063] It can be seen from Tables 4 and 5 that the reference solution is stable when placed at room temperature for 42 hours, and the test solution is stable when placed at room temperature for 39 hours.

[0064] (3) Linearity test

[0065] The linearity of the ethyl paraben reference substance at the limit concentration of 10% to 200% was verified, and the results are shown in Table 6. The linear regression graph is shown in Figure 2 shown.

[0066] Table 6 Ethyl Hydroxybenzoate Methodology - Linearity Test

[0067]

[0068] From Table 6 and Figure 2 It can be seen that ethylparaben has a linear relationship with the peak area in the concentration range of 1.0123 to 20.246 μg / ml, R 2 The linear relationship is good.

[0069] (4) Accuracy test

[0070] Recovery rate stock solution: Accurately weigh 25.0 mg of ethyl hydroxybenzoate reference substance, place it in a 50 ml volumetric flask, dissolve it in 50% acetonitrile and dilute to the scale, and shake well.

[0071] Recovery solution: Accurately measure 1ml, 2ml and 3ml of the recovery stock solution and 1.0g of blank auxiliary material, respectively, and place them in 10ml volumetric bottles, add ethanol to about 80% of the volume of the bottle, ultrasonicate for 10 minutes, dilute to the mark with ethanol, shake well, centrifuge at 8000 rpm for 10 minutes, accurately measure 2ml of the supernatant, place in a 20ml volumetric bottle, dilute to the mark with 50% acetonitrile, and shake well. Prepare 3 copies in parallel, and the recovery results are shown in Table 7;

[0072] Table 7 Recovery results

[0073]

[0074] As can be seen from Table 6, the recovery rate of ethyl hydroxybenzoate is between 85% and 110%, and the RSD of the recovery rate is 0.56%, which is less than 5.0%, meeting the requirements.

[0075] (5) Durability test

[0076] The reference solution and the test solution were taken to test the durability of different column temperatures, different flow rates and different instruments. The experimental results are shown in Table 8.

[0077] Table 8 Durability results

[0078]

[0079] It can be seen from Table 8 that ethylparaben has good durability under different test conditions.

[0080] Comparative Example 1

[0081] (1) The instruments and reagents are the same as those in Example 1;

[0082] (2) Chromatographic conditions: The chromatographic column used was 4.6 mm × 250 mm, 5 μm in size, and the rest was the same as in Example 1;

[0083] (3) Sample processing

[0084] Emulsion breaking and dilution solvents are ethanol

[0085] Test solution: Take about 1.0g of the product, accurately weigh it, put it in a 10ml volumetric flask, add about 7ml of ethanol solution, ultrasonicate for 10 minutes, dilute to the scale with ethanol solution, shake well, centrifuge at 4000 rpm for 20 minutes, accurately measure 2ml of the supernatant, put it in a 20ml volumetric flask, dilute to the scale with ethanol solution, shake well, filter, and take the filtrate.

[0086] The characteristic spectrum of ethyl paraben reference substance is as follows Figure 3 .

[0087] Comparative Example 2

[0088] (1) The instruments, reagents and sample processing were the same as those in Example 1;

[0089] (2) Chromatographic conditions: The chromatographic column used was Agilent ZORBAX Eclipse XDB-C18 (4.6 mm×250 mm, 5 μm), and the other conditions were the same as those in Example 1. The characteristic spectrum of the ethylparaben reference substance was obtained as follows: Figure 4 .

[0090] The demulsification effect of the sample in comparative example 1 can meet the requirements, as shown by the characteristic spectrum of the ethyl hydroxybenzoate reference substance. Figure 3 It can be seen that the peak shape of ethyl paraben is poor; Comparative Example 2 is characterized by the ethyl paraben reference substance spectrum Figure 4 It can be seen that the peak time of ethylparaben is too early; Example 1 overcomes the problems of emulsion demulsification and detection of antibacterial agents in emulsions, and at the same time overcomes the chromatographic parameter problems of Comparative Examples 1 and 2, and is more suitable for the detection of ethylparaben in dimethicone emulsions.

[0091] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for detecting ethylparaben in dimethicone emulsion, characterized in that: The following steps are involved: (1) Ultrasonic demulsification: accurately weigh a sample of dimethicone emulsion, place it in a volumetric bottle, add an organic solvent and ultrasonically dissolve it, then continue to add solvent to dilute to the scale to obtain a dimethicone emulsion dilution, shake well, and centrifuge to obtain a supernatant; (2) Dilution: Accurately measure the supernatant and place it in a volumetric flask, dilute it to the mark with acetonitrile solution, shake well to obtain an acetonitrile dilution, filter, and take the filtrate as the test solution; (3) Detection: Inject the test solution into a liquid chromatograph for detection.

2. The method for detecting ethylparaben in dimethicone emulsion according to claim 1, characterized in that: The organic solvent in step (1) is an ethanol aqueous solution; the volume concentration of ethanol in the ethanol aqueous solution is 70-80%.

3. The method for detecting ethylparaben in dimethicone emulsion according to claim 1, characterized in that: The concentration of the dimethicone emulsion in the dimethicone emulsion diluent of step (1) is 0.095 to 0.105 g / mL.

4. The method for detecting ethylparaben in dimethicone emulsion according to claim 1, characterized in that: The centrifugal speed in step (1) is 4000-4500 rpm, and the centrifugal time is 20-25 minutes.

5. The method for detecting ethylparaben in dimethicone emulsion according to claim 1, characterized in that: The volume concentration of acetonitrile in the acetonitrile solution in step (2) is 50%.

6. The method for detecting ethylparaben in dimethicone emulsion according to claim 1, characterized in that: The concentration of the supernatant in the acetonitrile dilution in step (2) is 0.1 mL / mL.

7. The method for detecting ethylparaben in dimethicone emulsion according to claim 1, characterized in that: The chromatographic conditions of the liquid chromatography in step (3) are: Chromatographic column: Octadecylsilane bonded silica gel is used as filler, and the column parameters are CAPCELL PAK C184.6mm×150mm, 5μm; Mobile phase: 1% glacial acetic acid solution as mobile phase A and acetonitrile as mobile phase B for gradient elution; Column temperature: 50°C; Detection wavelength: 254nm; Injection volume: 50ul.

8. The method for detecting ethylparaben in dimethicone emulsion according to claim 7, characterized in that: The gradient elution method is: 0→6 minutes, mobile phase A and mobile phase B are 50% respectively; 7→15 minutes, mobile phase A and mobile phase B are 15% and 85% respectively; 15.1→25 min, mobile phase A and mobile phase B were 50% each.

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