Method for detecting acetaldehyde in ethyl cellulose and sodium valproate tablets

Abstract

The invention discloses a method for detecting acetaldehyde in ethyl cellulose and sodium valproate tablets, which comprises the following steps: step 1, pre-treating a sample to obtain a test solution; 2, preparing an acetaldehyde contrast solution; and step 3, injecting the test solution into gas chromatography, and detecting. According to the method disclosed by the invention, the acetaldehyde in the ethyl cellulose and sodium valproate tablets is quantitatively detected by adopting the gas chromatography for the first time. A detailed method verifies that the gas chromatography detection method is suitable for quantitative analysis of acetaldehyde in ethyl cellulose and sodium valproate tablets under the laboratory condition.

Description

Technical Field

[0001] The invention relates to the technical field of acetaldehyde detection, and in particular to a method for detecting acetaldehyde in ethyl cellulose and sodium valproate tablets. Background Art

[0002] The existing acetaldehyde test item in ethyl cellulose is derived from Part IV P569-570 of the 2020 edition of the "Chinese Pharmacopoeia". The test method for acetaldehyde in ethyl cellulose is: take 3.0g of this product, place it in a 250ml stoppered conical flask, add 10ml of water, seal it, and stir for 1 hour. After standing for 24 hours, filter, dilute with water to 100ml, shake well, accurately measure 5ml, place in a 25ml volumetric flask, add 5ml of 0.05% methylbenzothiazolone hydrazone hydrochloride solution, heat in a 60℃ water bath for 5 minutes, add ferric chloride-aminosulfonic acid solution (take 1g of ferric chloride and aminosulfonic acid, add 100ml of water to dissolve), continue heating in a 60℃ water bath for 5 minutes, cool, dilute with water to the scale, shake well, and use it as the test solution; accurately measure 5.0ml of acetaldehyde reference solution (accurately weigh 1.0g of acetaldehyde, dilute with water to 100ml, shake well, accurately measure 5ml, place in a 500ml volumetric flask, dilute with water to the scale, shake well, accurately measure 3ml, place in a 100ml volumetric flask, dilute with water to the scale, shake well, and obtain. Freshly prepared before use) and operate in the same way. If color is developed, the color of the test solution shall not be darker than that of the reference solution (0.01%). This test method is a colorimetric method. According to the test, it can only determine whether the acetaldehyde in ethyl cellulose exceeds the limit requirement of 0.01%, and cannot determine the specific content of acetaldehyde.

[0003] Ethyl cellulose is an auxiliary material for producing solid preparations of sodium valproate tablets, but the prior art does not have a method for determining acetaldehyde in solid preparations of sodium valproate tablets. Therefore, those skilled in the art are in urgent need of studying a method for detecting acetaldehyde in ethyl cellulose and sodium valproate tablets. Summary of the invention

[0004] The purpose of the present invention is to provide a method for detecting acetaldehyde in ethyl cellulose and sodium valproate tablets in view of the deficiencies in the prior art.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] Provided is a method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets, comprising the following steps:

[0007] Step 1, performing sample pretreatment to obtain a test solution;

[0008] Step 2, preparing an acetaldehyde control solution;

[0009] Step 3, injecting the test solution into a gas chromatograph for detection;

[0010] The chromatographic conditions are:

[0011] Chromatographic column: Agilent DB-624; carrier gas: nitrogen; column flow rate: 4.5-5.3 ml / min; split ratio: (3-5):1; inlet temperature: 200-220°C; detector temperature: 280-300°C; column temperature: starting temperature 40-50°C, hold for 5-10 minutes, increase the temperature to 240-260°C at 20-30°C per minute, hold for 5-10 minutes; headspace equilibrium temperature: 80-90°C; equilibrium time: 30-40 minutes.

[0012] Furthermore, the chromatographic conditions are:

[0013] Chromatographic column: Agilent DB-624, 0.530mm×30m, 3.0μm; carrier gas: nitrogen; column flow rate: 5.3ml / min; split ratio: 5:1; inlet temperature: 200℃; detector temperature: 280℃; column temperature: starting temperature 40℃, hold for 5 minutes, increase to 240℃ at 20℃ per minute, hold for 5 minutes; headspace equilibrium temperature: 80℃; equilibrium time: 30 minutes.

[0014] Furthermore, the sample is sodium valproate tablets or ethyl cellulose.

[0015] Furthermore, the solvent used in the pretreatment is deionized water.

[0016] Furthermore, the acetaldehyde concentration in the control solution is 0.36-0.50 μg / ml.

[0017] Furthermore, the injection volume of the control solution is 5-8 ml.

[0018] Furthermore, the injection volume of the test solution is 5-8 ml.

[0019] The present invention adopts the above technical solution, and has the following technical effects compared with the prior art:

[0020] The present invention adopts gas chromatography for the first time to quantitatively detect acetaldehyde in ethyl cellulose and sodium valproate tablets, and through detailed method verification, it is proved that the gas chromatography detection method is suitable for quantitative analysis of acetaldehyde in ethyl cellulose and sodium valproate tablets under the laboratory conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is the blank spectrum in Example 4.

[0022] Figure 2 This is the reference spectrum in Example 4.

[0023] Figure 3 This is the sample spectrum of the sodium valproate tablets in Example 4.

[0024] Figure 4 This is the ethyl cellulose sample spectrum in Example 4. DETAILED DESCRIPTION

[0025] The present invention is further described below in conjunction with specific embodiments, but is not intended to be limiting of the present invention. It should be noted that the embodiments and features in the embodiments of the present invention may be combined with each other without conflict.

[0026] Example 1

[0027] This embodiment provides a method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets, which is as follows:

[0028] 1. Acetaldehyde: (Note: The control solution is sealed and stored at 2-8°C and is stable within 78 hours; the solution should be immediately filled into a headspace bottle after preparation, sealed and stored at 2-8°C, and the time from loading to injection should not exceed 6 hours).

[0029] 2. Blank: Accurately take 5 ml of water and place it in a 20 ml headspace bottle, seal it, and you are done.

[0030] 3. Control solution: accurately weigh 1.2g of acetaldehyde, dilute to 100ml with water, shake well, accurately measure 3ml, place in a 1000ml volumetric flask, dilute to scale with water, shake well, accurately measure 5ml, place in a 500ml volumetric flask, dilute to scale with water, shake well; the solution is ready. Prepare fresh before use as the control solution (0.36μg / ml). Accurately take 5ml of the control solution, place in a 20ml headspace bottle, seal, and the solution is ready.

[0031] 4. Test solution (sodium valproate tablets) a: Take 8 tablets of this product, remove the coating, accurately weigh, place in a 100ml stoppered conical bottle, add 10ml of water, seal, and stir for 1 hour; after standing for 24 hours, centrifuge, take 5ml of the supernatant and dilute to 10ml with water as the test solution (containing 0.48mg / ml of ethyl cellulose). Accurately take 5ml of the test solution, place in a 20ml headspace bottle, seal, and obtain.

[0032] 5. Test solution (ethyl cellulose) b: Take 3g of this product, place it in a 250ml stoppered conical flask, add 10ml of water, stopper, stir for 1 hour; after standing for 24 hours, filter, dilute with water to 100ml, shake well, measure 5ml and place it in a 50ml volumetric flask, add water and dilute to the scale as the test solution (3mg / ml). Accurately take 5ml of the test solution, place it in a 20ml headspace bottle, seal it, and you have it.

[0033] 6. Chromatographic parameters

[0034] Chromatographic column: Agilent DB-624, 0.530mm×30m, 3.0μm; carrier gas: nitrogen; column flow rate: 5.3ml / min; split ratio: 5:1; inlet temperature: 200℃; detector temperature: 280℃; column temperature: starting temperature 40℃, hold for 5 minutes, increase to 240℃ at 20℃ per minute, hold for 5 minutes; headspace equilibrium temperature: 80℃; equilibrium time: 30 minutes.

[0035] 7. Calculation formula

[0036]

[0037] Standard Deviation

[0038] Relative standard deviation

[0039]

[0040] Wherein, Sa is the peak area of ​​the test sample; St is the peak area of ​​the control; Mt is the weight of the control, g; Ma is the weight of the test sample, g; and P is the purity of the control.

[0041] Example 2 System suitability and specificity

[0042] The injection sequence is shown in Table 1 below:

[0043] Table 1

[0044] Serial Number Sample name Number of injection needles 1 blank 1 stitch or more 2 Control solution 1 (0.36 μg / ml) 5-pin 3 Control solution 2 (0.36 μg / ml) 1 needle 4 blank 1 stitch or more 5 Test solution a 1 needle 6 Test solution b 1 needle 7 blank 1 stitch or more

[0045] Judgment criteria: The RSD of the main peak area in the reference solution for 5 consecutive times should be less than 10%, and the St2 recovery rate should be 90-110%. The separation degree between the main peak and the impurity peak in the reference solution should meet the requirements, and the number of main peak plates should be greater than 5000; the blank should have no interference with the product test (acetaldehyde peak).

[0046] Test results (as shown in Table 2-Table 4):

[0047] Table 2

[0048]

[0049]

[0050] Table 3

[0051]

[0052] Table 4: Specificity

[0053]

[0054] Example 3 LOQ, LOD, Linearity

[0055] Control stock solution: accurately weigh 1.2g of acetaldehyde, dilute to 100ml with water, shake well, accurately measure 3ml, place in a 1000ml volumetric flask, dilute to scale with water, shake well, accurately measure 10ml, place in a 100ml volumetric flask, dilute to scale with water, shake well; (3.6μg / ml) is obtained. Prepare fresh before use as the control stock solution.

[0056] Prepare the solution according to Table 5:

[0057] Table 5

[0058] Linear Concentration (μg / ml) Linear stock solution volume (ml) Volume of measuring flask (ml) L-10％ 0.036 2 200 L-50％ 0.18 5 100 L-80％ 0.288 4 50 L-100％ 0.36 5 50 L-120％ 0.432 6 50 L-150％ 0.54 7.5 50 L-180％ 0.648 9 50

[0059] LOQ: Take 10% of the control solution (0.036 μg / ml) under the linear term and inject it 6 times.

[0060] LOD: Take 10% of the control solution under the linear item, measure 15 ml and place it in a 50 ml volumetric flask (0.011 μg / ml), and inject 3 times.

[0061] The injection sequence is shown in Table 6 below:

[0062] Table 6

[0063] Serial number name Injection times 1 blank 1 stitch or more 2 Control solution 1 (0.36 μg / ml) 5-pin 3 Control solution 2 (0.36 μg / ml) 1 needle 4 blank 1 stitch or more 5 LOD 3-pin 6 LOQ 6-pin 7 10％ 1 needle 8 50％ 1 needle 9 80％ 1 needle 10 100％ 1 needle 11 120％ 1 needle 12 150％ 1 needle 13 180％ 1 needle 14 blank 1 stitch or more

[0064] LOD: signal-to-noise ratio ≈3:1;

[0065] LOQ: RSD of acetaldehyde peak area in 6 injections of solution shall not be greater than 15%, signal-to-noise ratio ≈ 10:1;

[0066] Linear: R 2 ≥0.990, the intercept shall not be greater than 25% of the 100% peak area.

[0067] The test results are shown in Tables 7 to 9 below:

[0068] Table 7: LOD test results

[0069]

[0070] Table 8: LOQ test results

[0071]

[0072]

[0073] Table 9: Linearity test results

[0074]

[0075] Example 4 Precision (Repeatability a / b)

[0076] Prepare 6 parts of test solution a and 6 parts of test solution b:

[0077] Test solution (sodium valproate tablets) a: Take 8 tablets of this product, remove the coating, weigh accurately, place in a 100ml stoppered conical bottle, add 10ml of water, seal, and stir for 1 hour; after standing for 24 hours, centrifuge, take 5ml of the supernatant and dilute to 10ml with water as the test solution (containing 0.48mg / ml of ethyl cellulose). Accurately take 5ml of the test solution, place in a 20ml headspace bottle, seal, and you are done. (Prepare 6 portions of test solution in the same way)

[0078] Test solution (ethyl cellulose) b: Take 3g of this product, place it in a 250ml stoppered conical flask, add 10ml of water, seal it, and stir for 1 hour; after standing for 24 hours, filter, dilute with water to 100ml, shake well, measure 5ml and place it in a 50ml volumetric flask, add water and dilute to the scale as the test solution (3mg / ml). Accurately take 5ml of the test solution, place it in a 20ml headspace bottle, seal it, and you have it. (Prepare 6 test solutions in the same way)

[0079] The injection sequence is shown in Table 10 below:

[0080] Table 10

[0081]

[0082] Judgment criteria: meet system requirements and meet quality standard requirements; the RSD of acetaldehyde content in 6 test samples shall not be greater than 40%.

[0083] The test results are shown in Tables 11 and 12 below:

[0084] Table 11: Precision (repeatability a) test results

[0085]

[0086] Table 12: Precision (repeatability b) test results

[0087]

[0088] Example 5 Accuracy a / b (specified recovery)

[0089] Solution preparation (a):

[0090] Control stock solution: accurately weigh 1.2g of acetaldehyde, dilute to 100ml with water, shake well, accurately measure 3ml, place in a 1000ml volumetric flask, dilute to scale with water, shake well, accurately measure 10ml, place in a 100ml volumetric flask, dilute to scale with water, shake well; the solution is ready. Prepare fresh before use as control stock solution (3.6ug / ml).

[0091] Test sample stock solution: Take 64 tablets of this product, remove the coating, weigh accurately, place in a 250ml stoppered conical flask, add 80ml of water, seal, and stir for 1 hour. After standing for 24 hours, centrifuge and take the supernatant for test sample stock solution.

[0092] Unspecified test sample solution: Take 5 ml of the test sample stock solution and place it in a 10 ml volumetric flask, add water to dilute to the scale, shake well, and use it as the unspecified test sample solution (1 portion).

[0093] 80% spiked test solution: Take 5 ml of supernatant and 0.8 ml of control stock solution and place them in the same 10 ml volumetric flask, add water to dilute to the mark, shake well, and use as the test solution. (Prepare 3 portions of spiked test solution in the same way).

[0094] 100% spiked test solution: Take 5 ml of supernatant and 1 ml of control stock solution respectively and place them in the same 10 ml volumetric flask, dilute to the mark with water, shake well, and use as the test solution. (Prepare 3 portions of spiked test solution in the same way).

[0095] 120% spiked test solution: Take 5 ml of supernatant and 1.2 ml of control stock solution and place them in the same 10 ml volumetric flask, dilute to the mark with water, shake well, and use as the test solution. (Prepare 3 portions of spiked test solution in the same way).

[0096] Solution preparation (b)

[0097] Test sample stock solution: Take 3g of the product, place in a 250ml stoppered conical flask, add 10ml of water, stopper, and stir for 1 hour. After standing for 24 hours, filter and dilute with water to 100ml. Shake well and use as the test sample stock solution.

[0098] Unspecified test solution: Take 5 ml of the test solution and place it in a 50 ml volumetric flask, add water to dilute to the mark, shake well, and use it as the unspecified test solution (1 portion)

[0099] 80% spiked test solution: Take 5 ml of the test solution and 4 ml of the control solution and place them in the same 50 ml volumetric flask, add water and dilute to the mark to serve as the 80% spiked test solution. (3 portions)

[0100] 100% spiked test solution: Take 5 ml of the test solution and 5 ml of the control solution and place them in the same 50 ml volumetric flask, add water and dilute to the mark to serve as the 100% spiked test solution. (3 portions)

[0101] 120% spiked test solution: Take 5 ml of the test solution and 6 ml of the control solution and place them in the same 50 ml volumetric flask, add water and dilute to the mark to serve as the 120% spiked test solution. (3 portions)

[0102] The injection sequence is shown in Table 13 below:

[0103] Table 13

[0104] Serial Number Sample name Number of injection needles 1 blank 1 stitch or more 2 Control solution 1 (0.36 μg / ml) 5-pin 3 Control solution 2 (0.36 μg / ml) 1 needle 4 blank 1 stitch or more 5 Test solution (a) not spiked 1 needle 6 Test solution (a) 80% spiked 1-3 1 needle each 7 Test solution (a) 100% spiked 1-3 1 needle each 8 Test solution (a) 120% spiked 1-3 1 needle each 9 blank 1 stitch or more 10 Test solution (b) not spiked 1 needle 11 Test solution (b) 80% spiked 1-3 1 needle each 12 Test solution (b) 100% spiked 1-3 1 needle each 13 Test solution (b) 120% spiked 1-3 1 needle each 14 blank 1 stitch or more

[0105] Judgment criteria: meet the system requirements; for test sample a, the recovery rate of acetaldehyde in 9 spiked test sample solutions should be within 75% to 120%, and the RSD should be no more than 10%; for test sample b, the recovery rate of acetaldehyde in 9 spiked test sample solutions should be within 85% to 110%, and the RSD should be no more than 10%.

[0106] The test results are shown in Tables 14 and 15 below:

[0107] Table 14: Accuracy a test results

[0108]

[0109] Table 15: Accuracy b test results

[0110]

[0111]

[0112] Example 6 Solution Stability

[0113] The preparation of the control solution is shown under the preparation of the solution in "Example 1";

[0114] Take the control solution and inject it at 24h, 48h and 72h respectively; if the result at any time point exceeds the predetermined standard, no subsequent time point detection will be performed.

[0115] The sequence is as shown in Table 16:

[0116] Table 16

[0117] Serial Number Sample name Number of injection needles 1 blank 1 stitch or more 2 Control solution 1 (0.36 μg / ml) 5-pin 3 Control solution 2 (0.36 μg / ml) 1 needle 4 blank 1 stitch or more 5 Control solution (24h, 48h, 72h) 1 needle

[0118] Judgment criteria: meet system requirements; the control solution content should be 99.5% (COA) ± 10%.

[0119] The test results are shown in Table 17:

[0120] Table 17

[0121]

[0122] Example 7 Durability

[0123] The solution preparation is shown in "Example 1" under the solution preparation;

[0124] Table 18: Durability test parameters are as follows

[0125] parameter Normal conditions Survey value Column flow 5.3ml / min 5.1ml / min, 5.5ml / min Headspace temperature 80℃ 75℃，85℃ Starting temperature 40℃ 38℃，42℃

[0126] The sequence is shown in Table 19:

[0127] Table 19

[0128] Serial Number Sample name Number of injection needles 1 blank 1 stitch or more 2 Control solution 5-pin 3 Test solution (a) 1 needle 4 Test solution (b) 1 needle

[0129] Satisfy system requirements and meet quality standards;

[0130] 1. The ratio of acetaldehyde content in the test solution a to that under normal conditions should be between 75% and 120%.

[0131] 2. The ratio of acetaldehyde content in the test solution b to that under normal conditions should be between 85% and 110%. The test results are shown in Table 20-Table 22:

[0132] Table 20: Column flow rates

[0133]

[0134] Table 21: Starting temperature

[0135]

[0136]

[0137] Table 22: Headspace Temperature

[0138]

[0139] The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the contents of the specification of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets, characterized in that: The steps include: Step 1, performing sample pretreatment to obtain a test solution; Step 2, preparing an acetaldehyde control solution; Step 3, injecting the test solution into a gas chromatograph for detection; The chromatographic conditions are: Chromatographic column: Agilent DB-624; carrier gas: nitrogen; column flow rate: 4.5-5.3 ml / min; split ratio: (3-5):1; inlet temperature: 200-220°C; detector temperature: 280-300°C; column temperature: starting temperature 40-50°C, hold for 5-10 minutes, increase the temperature to 240-260°C at 20-30°C per minute, hold for 5-10 minutes; headspace equilibrium temperature: 80-90°C; equilibrium time: 30-40 minutes.

2. The method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets according to claim 1, characterized in that: The chromatographic conditions are: Chromatographic column: Agilent DB-624, 0.530 mm × 30 m, 3.0 μm; carrier gas: nitrogen; column flow rate: 5.3 ml / min; split ratio: 5:1; injection port temperature: 200 °C; detector temperature: 280 °C; Column temperature: initial temperature 40°C, hold for 5 minutes, increase the temperature to 240°C at 20°C per minute, hold for 5 minutes; headspace equilibrium temperature: 80°C; equilibrium time: 30 minutes.

3. The method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets according to claim 1, characterized in that: The sample is sodium valproate tablets or ethylcellulose.

4. The method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets according to claim 1, characterized in that: The solvent used in the pretreatment is deionized water.

5. The method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets according to claim 1, characterized in that: The acetaldehyde concentration in the control solution was 0.36-0.50 μg / ml.

6. The method for detecting acetaldehyde in ethylcellulose and sodium valproate tablets according to claim 5, characterized in that: The injection volume of the control solution is 5-8 ml.

7. The method for detecting acetaldehyde in ethyl cellulose and sodium valproate tablets according to claim 1, characterized in that: The injection volume of the test solution is 5-8 ml.

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