Detection method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops

Abstract

The invention discloses a detection method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops, which comprises the following steps: step 1, setting chromatographic conditions: heating to 220 DEG C at a rate of 20 DEG C / min by using a capillary column with 6% propylphenyl-94% dimethyl polysiloxane as a stationary liquid, and maintaining for 10 minutes; step 2, solution preparation: preparing a blank solvent, a reference solution and a test solution; step 3, determination: taking the blank solvent, the reference substance solution and the test solution for sample introduction analysis, and recording a chromatogram; step 4, limit: calculating by peak area according to an external standard method, wherein the content of ethylene glycol is not more than 0.062%, and the content of diethylene glycol is not more than 0.025%; the method disclosed by the invention is simple, convenient, rapid, high in accuracy and good in specificity, can be used for simultaneously determining the contents of ethylene glycol and diethylene glycol in the cetirizine hydrochloride drops, and is suitable for quality research and control of the cetirizine hydrochloride drops.

Description

Technical Field

[0001] The invention relates to the technical field of detection of ethylene glycol and diethylene glycol, and specifically to a detection method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops. Background Art

[0002] Cetirizine hydrochloride drops are used to treat seasonal rhinitis, perennial allergic rhinitis, non-nasal conjunctivitis, and allergic symptoms such as itching and urticaria. Propylene glycol and glycerol are used in the formulation of cetirizine hydrochloride drops. Ethylene glycol and diethylene glycol are common impurities in raw materials such as propylene glycol, glycerol, and polyethylene glycol. Ethylene glycol is colorless and odorless and has low toxicity itself, but the products formed after its metabolism in the liver are highly toxic and can cause damage to the nervous system, heart, liver, and kidney function. Although diethylene glycol is a low-toxic chemical, high doses can cause central nervous system depression and liver and kidney damage. Therefore, controlling the content of ethylene glycol and diethylene glycol in cetirizine hydrochloride drops is essential.

[0003] At present, the ethylene glycol and diethylene glycol detection methods in various countries' pharmacopoeias are difficult to apply to the determination of preparations with complex components, and there is no report in the literature on a method for simultaneously determining the ethylene glycol and diethylene glycol contents in cetirizine hydrochloride drops.

[0004] In summary, it is urgent to develop a rapid and effective detection method for the simultaneous determination of ethylene glycol and diethylene glycol in cetirizine hydrochloride drops. Summary of the Invention

[0005] The object of the present invention is to provide a method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops, so as to solve the problems raised in the above background technology.

[0006] To achieve the above object, the present invention provides the following technical solution: a method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops, comprising the following steps:

[0007] Step 1, chromatographic conditions: using a capillary column with 6% propylphenyl-94% dimethylpolysiloxane as the stationary phase, heating to 220°C at a rate of 20°C / min and maintaining for 10 minutes;

[0008] Step 2, solution preparation: prepare blank solvent, reference solution and test solution;

[0009] Step 3: Determination: Take blank solvent, reference solution, and test solution for analysis and record the chromatogram;

[0010] Step 4. Limits: Calculated by peak area using the external standard method, the ethylene glycol content must not exceed 0.062%, and the diethylene glycol content must not exceed 0.025%.

[0011] Preferably, the step 1 is a capillary column with 6% propylphenyl-94% dimethylpolysiloxane as the stationary phase, a flow rate of 1.5 ml / min, a split ratio of 20:1, a starting temperature of 100°C, maintained for 5 minutes, heated to 220°C at a rate of 20°C / min, and maintained for 10 minutes; the injection port temperature is 200°C, the detector temperature is 250°C, and the injection volume is 2 μl.

[0012] Preferably, the chromatographic column in step 1 is DB-624, with an inner diameter and length of 30m×0.32mm and a particle size of 1.8μm, or a chromatographic column with similar polarity.

[0013] Preferably, the solution preparation in step 2 is specifically as follows:

[0014] Blank solvent: methanol;

[0015] Reference substance solution: accurately weigh 155 mg of ethylene glycol and 62.5 mg of diethylene glycol, place in a 50 ml volumetric flask, dilute to the mark with methanol, and shake well to prepare the reference substance stock solution; accurately weigh 1 ml of the reference substance stock solution and place in a 50 ml volumetric flask, dilute to the mark with methanol, and shake well to prepare a reference substance solution containing 0.062 mg of ethylene glycol and 0.025 mg of diethylene glycol per 1 ml;

[0016] Test solution: Take 1.0g of this product, accurately weigh it, place it in a 10ml volumetric flask, add methanol to dilute to the scale, shake well, and obtain the solution.

[0017] Preferably, the step three is specifically as follows: injecting a blank solvent, a reference solution, and a test solution into a gas chromatograph respectively, recording a chromatogram, and the peak areas of ethylene glycol and diethylene glycol in the chromatogram of the test solution shall not be greater than the peak areas of ethylene glycol and diethylene glycol in the reference solution.

[0018] Preferably, in step 4, the peak area is calculated using the external standard method as follows:

[0019]

[0020]

[0021] Where: A 样 、A 对 M is the peak area of ethylene glycol and diethylene glycol in the test and reference solutions; 对 is the sample weight of the reference substance, in mg; M 样 is the sample weight of the test sample, in mg; V 样 、V 对 is the dilution multiple of the test and reference substances; C 对is the concentration of each component of the reference solution, in mg / ml; a% is the content of each reference substance; f is the ratio of the concentration of each component of the reference solution to the peak area, and the average value is substituted into the calculation.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The invention is simple, rapid, highly accurate and good in specificity, can simultaneously determine the contents of ethylene glycol and diethylene glycol in cetirizine hydrochloride drops, and is suitable for quality research and control of cetirizine hydrochloride drops. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 is a chromatogram of a blank solvent of the present invention;

[0025] Figure 2 is a chromatogram of a reference solution of the present invention;

[0026] Figure 3 is a chromatogram of the test solution of the present invention;

[0027] Figure 4 is a linear graph of the ethylene glycol concentration range of the present invention;

[0028] Figure 5 It is a linear graph of the diethylene glycol concentration range of the present invention. DETAILED DESCRIPTION

[0029] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0030] See also Figure 1-5 The present invention provides a method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops, comprising the following steps:

[0031] Step 1. Chromatographic conditions: capillary column with 6% propylphenyl-94% dimethylpolysiloxane as the stationary phase, flow rate 1.5 ml / min, split ratio 20:1, starting temperature 100°C, hold for 5 minutes, heating to 220°C at a rate of 20°C / min, hold for 10 minutes; injection port temperature 200°C, detector temperature 250°C, injection volume 2 μl; chromatographic column DB-624, column inner diameter and length 30 m × 0.32 mm, 1.8 μm particle size, or a column with similar polarity;

[0032] Step 2, solution preparation: prepare blank solvent, reference solution and test solution;

[0033] Blank solvent: methanol;

[0034] Reference substance solution: accurately weigh 155 mg of ethylene glycol and 62.5 mg of diethylene glycol, place in a 50 ml volumetric flask, dilute to the mark with methanol, and shake well to prepare the reference substance stock solution; accurately weigh 1 ml of the reference substance stock solution and place in a 50 ml volumetric flask, dilute to the mark with methanol, and shake well to prepare a reference substance solution containing 0.062 mg of ethylene glycol and 0.025 mg of diethylene glycol per 1 ml;

[0035] Test solution: Take 1.0g of the product, accurately weigh it, place it in a 10ml volumetric flask, add methanol to dilute to the scale, shake well, and obtain the solution;

[0036] Step 3: Determination: Take blank solvent, reference solution, and test solution for analysis and record the chromatogram;

[0037] Take blank solvent, reference solution, and test solution and inject them into gas chromatograph respectively, record the chromatogram, and the peak area of ethylene glycol and diethylene glycol in the chromatogram of the test solution shall not be larger than the peak area of ethylene glycol and diethylene glycol in the reference solution;

[0038] Step 4. Limits: Calculate by peak area according to the external standard method. The ethylene glycol content shall not exceed 0.062%, and the diethylene glycol content shall not exceed 0.025%. The formula for calculating by peak area according to the external standard method is:

[0039]

[0040] Where: A 样 、A 对 M is the peak area of ethylene glycol and diethylene glycol in the test and reference solutions; 对 is the sample weight of the reference substance, in mg; M 样 is the sample weight of the test sample, in mg; V 样 、V 对 is the dilution multiple of the test and reference substances; C 对 is the concentration of each component of the reference solution, in mg / ml; a% is the content of each reference substance; f is the ratio of the concentration of each component of the reference solution to the peak area, and the average value is substituted into the calculation.

[0041] Experimental results

[0042]

[0043]

[0044] No ethylene glycol was detected in this batch of samples, and the diethylene glycol content was 0.0021%, indicating that the samples were qualified.

[0045] Example 1: Specificity and system applicability

[0046] 1. Solution preparation

[0047] Blank solvent: methanol.

[0048] Ethylene glycol stock solution: Take 155 mg of ethylene glycol, accurately weigh it, place it in a 50 ml volumetric flask, add methanol to dilute to the scale, shake well, and obtain it.

[0049] Ethylene glycol positioning solution: Accurately measure 1 ml of ethylene glycol stock solution and place it in a 50 ml volumetric flask, add methanol to dilute to the scale, shake well, and the solution is ready.

[0050] Diethylene glycol stock solution: Take 62.5 mg of diethylene glycol, accurately weigh it, place it in a 50 ml volumetric flask, add methanol to dilute to the scale, shake well, and obtain it.

[0051] Diethylene glycol positioning solution: Accurately measure 1 ml of diethylene glycol stock solution and place it in a 50 ml volumetric flask, add methanol to dilute to the scale, and shake well.

[0052] Reference solution: Accurately measure 1 ml each of ethylene glycol and diethylene glycol stock solutions into a 50 ml volumetric flask, add methanol to dilute to the scale, and shake well.

[0053] Test solution: Take 1.0g of this product, accurately weigh it, place it in a 10ml volumetric flask, add methanol to dilute to the scale, shake well, and obtain the solution.

[0054] Spiked test solution: Take 1.0g of the product, accurately weigh it, place it in a 10ml volumetric flask, add 0.2ml each of ethylene glycol and diethylene glycol stock solutions, add methanol to dilute to the scale, shake well, and obtain the product.

[0055] 2. Sample injection analysis

[0056] Serial number name Number of servings Number of needle insertions 1 Blank solvent 1 ≥1 injection 2 Reference solution 1 1 needle 3 Positioning solution 1 each 1 needle each 4 Test solution 1 1 needle 5 Spiked test solution 1 1 needle

[0057] 3. Acceptable standards

[0058] The blank solution should not interfere with the sample test;

[0059] In the chromatogram of the reference solution, the order of peaks of the components is ethylene glycol, diethylene glycol;

[0060] The retention time of each component in the spiked test solution should be consistent with that of the single positioning solution.

[0061] 4. Results

[0062] Retention time (min) Ethylene glycol Diethylene glycol Reference solution 5.222 9.502 Ethylene glycol positioning solution 5.232 N / A Diethylene glycol positioning solution N / A 9.504 Spiked test solution 5.308 9.517

[0063] 5. Conclusion

[0064] The experimental data show that the blank solution has no interference with the sample test; the peak order in the reference solution is ethylene glycol and diethylene glycol; the retention time of each component in the spiked test solution is consistent with that of a single positioning solution, proving that the specificity and system applicability of the analytical method meet the requirements.

[0065] Example 2: Limit of Quantitation and Limit of Detection

[0066] 1. Solution preparation

[0067] Blank solution: methanol.

[0068] Quantitation limit solution: Accurately measure 1 ml of the reference solution under the specificity and system suitability items and place it in a 10 ml volumetric flask, add methanol to dilute to the scale, and shake well.

[0069] Detection limit solution: Accurately measure 3 ml of the quantification limit solution and place it in a 10 ml volumetric flask. Add methanol to dilute to the scale and shake well.

[0070] 2. Sample injection analysis

[0071]

[0072] 3. Acceptable standards

[0073] The S / N of the ethylene glycol and diethylene glycol peaks in the quantification limit solution should be ≥10. After 6 consecutive injections, the peak area RSD should be ≤15.0%, and the retention time RSD of each component should be ≤1.0%;

[0074] The S / N of ethylene glycol and diethylene glycol peaks in the detection limit solution should be ≥3.

[0075] 4. Results

[0076] 1) Limit of quantification

[0077]

[0078]

[0079] 2) Detection limit

[0080]

[0081] 5. Conclusion

[0082] 1) When the ethylene glycol concentration was 6.1407 μg / ml (equivalent to 0.00614% of the test sample), the S / N was 13.2-23.0, which was greater than 10. Six injections of this concentration solution showed a peak area RSD of 2.6% and a retention time RSD of 0.1%, indicating that this concentration could be used as the limit of quantification of ethylene glycol. When the ethylene glycol concentration was 1.8422 μg / ml (equivalent to 0.00184% of the test sample), the S / N was 4.4, which was greater than 3, indicating that this concentration could be used as the limit of detection of ethylene glycol.

[0083] 2) When the concentration of diethylene glycol was 2.4841 μg / ml (equivalent to 0.00248% of the test sample), the S / N was 10.5-18.3, which was >10. The solution at this concentration was injected continuously for 6 times, with the peak area RSD being 6.2% and the retention time RSD being 0.1%, indicating that this concentration can be used as the limit of quantification of diethylene glycol. When the concentration of diethylene glycol was 0.7452 μg / ml (equivalent to 0.00075% of the test sample), the S / N was 3.4, which was >3, indicating that this concentration can be used as the limit of detection of diethylene glycol.

[0084] The limits of quantification and detection were within the acceptable standards.

[0085] Example 3: Linearity and Range

[0086] 1. Solution preparation

[0087] Blank solution: methanol.

[0088] Quantitation limit solution: Accurately measure 1 ml of the reference solution under the specificity and system suitability items into a 10 ml volumetric flask, dilute to the mark with methanol, and shake well;

[0089] 50% linear solution: Accurately measure 0.5 ml of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, and shake well;

[0090] 80% linear solution: Accurately measure 0.8 ml of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, and shake well.

[0091] 100% linear solution: Accurately measure 1 ml of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, and shake well;

[0092] 150% linear solution: Accurately measure 1.5 ml of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, and shake well.

[0093] 200% linear solution: Accurately measure 2 ml of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, and shake well.

[0094] 2. Sample injection analysis

[0095] Serial number name Number of servings Number of injection needles 1 Blank solvent 1 ≥1 injection 2 Quantitative limit solution 1 1 needle 3 50% linear solution 1 1 needle 4 80% linear solution 1 1 needle 5 100% linear solution 1 1 needle 6 150% linear solution 1 1 needle 7 200% linear solution 1 1 needle

[0096] 3. Acceptable standards

[0097] In the concentration range from the limit of quantification to the 200% limit, the correlation coefficient r in the linear regression equation of ethylene glycol and diethylene glycol should be ≥ 0.990, and the absolute value of the ratio of the intercept to the 100% concentration response value should be ≤ 15.0%.

[0098] 4. Results

[0099] 1) Ethylene glycol

[0100]

[0101] 2) Diethylene glycol

[0102]

[0103] 5. Conclusion

[0104] Within the concentration range from the limit of quantification to the 200% limit, the correlation coefficients in the linear regression equations for ethylene glycol and diethylene glycol were 0.9996 and 0.9999, respectively, both greater than 0.990. The absolute values of the ratios of the intercept to the 100% concentration response were 1.0% and 1.4%, respectively, both less than 15.0%. Good linearity was observed for ethylene glycol in the concentration range of 6.14 μg / ml to 122.81 μg / ml, and for diethylene glycol in the concentration range of 2.48 μg / ml to 49.68 μg / ml.

[0105] Example 4: Precision (injection precision)

[0106] 1. Solution preparation

[0107] Blank solution: methanol;

[0108] Reference solution: Accurately measure 1 ml each of ethylene glycol and diethylene glycol stock solutions into a 50 ml volumetric flask, add methanol to dilute to the scale, and shake well.

[0109] 2. Sample injection analysis

[0110]

[0111] 3. Acceptable standards

[0112] The reference solution was injected 6 times in succession. The RSD of the ethylene glycol and diethylene glycol peak areas should be ≤10.0%. The RSD of the retention time should be ≤1.0%.

[0113] 4. Results

[0114]

[0115] 5. Conclusion

[0116] The reference solution was injected six times continuously. The RSDs of the ethylene glycol and diethylene glycol peak areas were 2.2% and 1.7%, respectively, both less than 10.0%. The RSDs of the ethylene glycol and diethylene glycol retention times were 0.1% and 0.1%, respectively, both less than 1.0%. The injection precision was good.

[0117] Example 5: Precision (Repeatability)

[0118] 1. Solution preparation

[0119] Blank solution: methanol.

[0120] Reference solution: Accurately measure 1 ml each of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, shake well, and prepare two replicates.

[0121] Spiked test solution: Take 1.0g of the product, accurately weigh it, and place it in a 10ml volumetric flask. Accurately add 0.2ml of the reference substance stock solution, then add methanol to dilute to the scale, shake well, and obtain 6 parallel copies.

[0122] 2. Sample injection analysis

[0123]

[0124] 3. Acceptable standards

[0125] The RSD of the recoveries of ethylene glycol and diethylene glycol should be ≤10.0% when 6 spiked samples are measured.

[0126] 4. Results

[0127] 1) Ethylene glycol

[0128]

[0129]

[0130] 2) Diethylene glycol

[0131]

[0132] 5. Conclusion

[0133] The recoveries of ethylene glycol and diethylene glycol were RSDs of 4.1% and 4.5%, respectively, for 6 spiked samples, both less than 10.0%, indicating good repeatability.

[0134] Example 6: Precision (Intermediate Precision)

[0135] 1. Solution preparation

[0136] Blank solution: methanol.

[0137] Reference solution: Accurately measure 1 ml each of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, shake well, and prepare two replicates.

[0138] Spiked test solution: Take 1.0g of the product, accurately weigh it, and place it in a 10ml volumetric flask. Accurately add 0.2ml of the reference substance stock solution, then add methanol to dilute to the scale, shake well, and obtain 6 parallel copies.

[0139] 2. Sample injection analysis

[0140]

[0141]

[0142] 3. Acceptable standards

[0143] When a single person measures 6 spiked samples, the RSD of the recoveries of ethylene glycol and diethylene glycol should be ≤10.0%; when two people measure 12 spiked samples, the RSD of the recoveries of ethylene glycol and diethylene glycol should be ≤10.0%.

[0144] 4. Results

[0145] 1) Ethylene glycol

[0146]

[0147]

[0148] 2) Diethylene glycol

[0149]

[0150]

[0151] 5. Conclusion

[0152] When a single person measured 6 spiked samples, the RSDs of ethylene glycol and diethylene glycol recoveries were 2.0% and 3.7%, respectively, both less than 10.0%; when a pair of people analyzed 12 spiked samples, the RSDs of ethylene glycol and diethylene glycol recoveries were 3.3% and 6.4%, respectively, both less than 10.0%, indicating good intermediate precision.

[0153] Example 7: Accuracy

[0154] 1. Solution preparation

[0155] Blank solution: methanol;

[0156] Reference solution: Accurately measure 1 ml each of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, shake well, and prepare two replicates.

[0157] Test solution: Take 1.0g of the product, accurately weigh it, place it in a 10ml volumetric flask, add methanol to dilute to the scale, shake well, and prepare 2 replicates.

[0158] Quantitation limit spiked test solution: Take 1.0g of the product, accurately weigh it, and place it in a 10ml volumetric flask. According to the quantitation limit result, add an appropriate amount of quantitation limit stock solution, then add methanol to dilute to the scale, shake well, and prepare 3 replicates.

[0159] 50% spiked test solution: Take 1.0g of the product, accurately weigh it, and place it in a 10ml volumetric flask. Accurately add 0.1ml each of diethanol and diethylene glycol stock solutions, then add methanol to dilute to the scale, shake well, and prepare 3 replicates.

[0160] 100% spiked test solution: Take 1.0g of the product, accurately weigh it, and place it in a 10ml volumetric flask. Accurately add 0.2ml each of diethanol and diethylene glycol stock solutions, then add methanol to dilute to the scale, shake well, and make 3 replicates.

[0161] 150% spiked test solution: Take 1.0g of the product, accurately weigh it, and place it in a 10ml volumetric flask. Accurately add 0.3ml each of diethanol and diethylene glycol stock solutions, then add methanol to dilute to the scale, shake well, and prepare 3 parallel copies.

[0162] 2. Sample injection analysis

[0163]

[0164]

[0165] 3. Calculation formula:

[0166]

[0167] 4. Acceptable standards

[0168] Within the concentration range of limit of quantification to 150.0%, the average recovery rate at the limit of quantification concentration level is between 70.0% and 130.0%, and the average recovery rate at other concentration levels is between 80.0% and 120.0%. The RSD of the recovery rate should be ≤15.0%.

[0169] 5. Results

[0170] 1) Ethylene glycol

[0171]

[0172]

[0173] 2) Diethylene glycol

[0174]

[0175]

[0176] 6. Conclusion

[0177] The average recoveries of ethylene glycol and diethylene glycol at the limit of quantification (LOQ) concentration were 100.0% and 100.2%, respectively, both within the range of 70.0% to 130.0%. At other concentrations, the average recoveries of ethylene glycol and diethylene glycol were 84.3% to 90.2% and 80.3% to 88.2%, respectively, both within the range of 80.0% to 120.0%. The maximum RSDs of the recoveries were 3.8% and 1.5%, respectively, both less than 15.0%. The accuracy was good.

[0178] Example 8: Solution stability

[0179] 1. Solution preparation

[0180] Blank solution: methanol.

[0181] Reference solution: Accurately measure 1 ml each of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, shake well, and prepare two replicates.

[0182] Spiked test solution: Take 1.0g of this product, accurately weigh it, and place it in a 10ml volumetric flask. Accurately add 0.2ml of the reference substance stock solution, then add methanol to dilute to the scale, shake well, and obtain 2 parallel copies.

[0183] The reference solution and the spiked test solution were placed at room temperature and injected at different time points for inspection.

[0184] 2. Sample injection analysis

[0185]

[0186] 3. Acceptable standards

[0187] The reference solution and the spiked test solution are placed at room temperature and injected at different times. The absolute value of the relative deviation of the ethylene glycol and diethylene glycol peak areas compared with 0h should be ≤10.0%.

[0188] 1) Ethylene glycol

[0189]

[0190]

[0191] 2) Diethylene glycol

[0192]

[0193]

[0194] 4. Conclusion

[0195] When the reference solution was stored at room temperature for 48 hours, the maximum absolute deviations of the ethylene glycol and diethylene glycol peak areas compared to those at 0 hours were 6.2% and 7.9%, respectively, both less than 10.0%. When the test solution was stored at room temperature for 48 hours, the maximum absolute deviations of the ethylene glycol and diethylene glycol peak areas compared to those at 0 hours were 7.2% and 2.5%, respectively, both less than 10.0%. The reference solution was stable for 48 hours at room temperature, and the spiked test solution was stable for 48 hours.

[0196] Example 9: Durability

[0197] 1. Solution preparation

[0198] Blank solution: methanol.

[0199] Reference solution: Accurately measure 1 ml each of the ethylene glycol and diethylene glycol stock solutions under the specificity and system suitability items into a 50 ml volumetric flask, dilute to the mark with methanol, shake well, and prepare two replicates.

[0200] Spiked test solution: Take 1.0 g of the product, accurately weigh it, place it in a 10 ml volumetric flask, add 0.2 ml each of ethylene glycol and diethylene glycol stock solutions, add methanol to dilute to the scale, shake well, and prepare 2 parallel copies.

[0201] 2. Changes in conditions

[0202]

[0203]

[0204] 3. Sample injection analysis (analyze once for each condition)

[0205]

[0206] 4. Acceptable standards

[0207] After changing the conditions (flow rate ± 0.2 ml / min, heating program ± 5 ° C, injection port temperature ± 5 ° C, detector temperature ± 5 ° C), the blank solution has no interference with the sample test. Compared with the normal conditions, the absolute value of the relative deviation of the ethylene glycol and diethylene glycol contents under the changed conditions should be ≤ 20.0%.

[0208] 5. Results

[0209]

[0210]

[0211] 6. Conclusion

[0212] After changing the conditions (flow rate ±0.2 ml / min, initial column temperature ±5°C, injection port temperature ±5°C, detector temperature ±5°C), the blank solution showed no interference with the ethylene glycol and diethylene glycol peak positions. Compared with normal conditions, the maximum absolute deviations of the ethylene glycol and diethylene glycol contents in the spiked samples under the changed conditions were 7.0% and 13.0%, respectively, both below 20.0%. This demonstrates excellent durability.

[0213] Verification conclusion:

[0214] The analytical method for ethylene glycol and diethylene glycol in cetirizine hydrochloride drops was validated, including tests on specificity and system suitability, quantification limit and detection limit, linearity and range, precision (injection precision, repeatability, intermediate precision), accuracy, solution stability, and durability. All validation results met the acceptance criteria, indicating that this method is suitable for the determination of ethylene glycol and diethylene glycol in cetirizine hydrochloride drops.

[0215] Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops, characterized in that: The following steps are involved: Step 1, chromatographic conditions: using a capillary column with 6% propylphenyl-94% dimethylpolysiloxane as the stationary phase, heating to 220°C at a rate of 20°C / min and maintaining for 10 minutes; Step 2, solution preparation: prepare blank solvent, reference solution and test solution; Step 3: Determination: Take blank solvent, reference solution, and test solution for analysis and record the chromatogram; Step 4. Limits: Calculated by peak area using the external standard method, the ethylene glycol content must not exceed 0.062%, and the diethylene glycol content must not exceed 0.025%.

2. The method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops according to claim 1, wherein: In step 1, a capillary column with 6% propylphenyl-94% dimethylpolysiloxane as the stationary phase was used, with a flow rate of 1.5 ml / min, a split ratio of 20:1, a starting temperature of 100°C, maintained for 5 minutes, and then heated to 220°C at a rate of 20°C / min and maintained for 10 minutes; the injection port temperature was 200°C, the detector temperature was 250°C, and the injection volume was 2 μl.

3. The method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops according to claim 1, wherein: The chromatographic column in step 1 is DB-624, with an inner diameter and length of 30m×0.32mm and a particle size of 1.8μm, or a chromatographic column with similar polarity.

4. The method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops according to claim 1, wherein: The solution preparation in step 2 is specifically as follows: Blank solvent: methanol; Reference substance solution: accurately weigh 155 mg of ethylene glycol and 62.5 mg of diethylene glycol, place in a 50 ml volumetric flask, dilute to the mark with methanol, and shake well to prepare the reference substance stock solution; accurately weigh 1 ml of the reference substance stock solution and place in a 50 ml volumetric flask, dilute to the mark with methanol, and shake well to prepare a reference substance solution containing 0.062 mg of ethylene glycol and 0.025 mg of diethylene glycol per 1 ml; Test solution: Take 1.0g of this product, accurately weigh it, place it in a 10ml volumetric flask, add methanol to dilute to the scale, shake well, and obtain the solution.

5. The method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops according to claim 1, wherein: The step three is specifically as follows: injecting a blank solvent, a reference solution, and a test solution into a gas chromatograph respectively, and recording a chromatogram; the peak areas of ethylene glycol and diethylene glycol in the chromatogram of the test solution shall not be greater than the peak areas of ethylene glycol and diethylene glycol in the reference solution.

6. The method for simultaneously determining ethylene glycol and diethylene glycol in cetirizine hydrochloride drops according to claim 1, wherein: In the step 4, the peak area is calculated using the external standard method as follows: Where: A 样 、A 对 M is the peak area of ethylene glycol and diethylene glycol in the test and reference solutions; 对 is the sample weight of the reference substance, in mg; M 样 is the sample weight of the test sample, in mg; V 样 、V 对 C is the dilution multiple of the test and reference substances; 对 is the concentration of each component of the reference solution, in mg / ml; a% is the content of each reference substance; f is the ratio of the concentration of each component of the reference solution to the peak area, and the average value is substituted into the calculation.

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