Method for detecting content of polyethylene glycol in compound polyethylene glycol electrolyte solution

Abstract

The invention discloses a method for detecting the content of polyethylene glycol in a compound polyethylene glycol electrolyte solution, and relates to the field of methods for detecting the content of polyethylene glycol, the detection method adopts a liquid chromatography method, in the liquid chromatography method, an ethanol solution is adopted as a mobile phase, the ethanol solution is used for separating potassium ions and / or sodium ions in the compound polyethylene glycol electrolyte solution from polyethylene glycol. According to the method disclosed by the invention, pure water or a mobile phase added with a proper amount of bacteriostatic agent in the prior art is replaced by the ethanol solution, so that the polyethylene glycol is separated from sodium ions and potassium ions, and the problems of poor specificity and poor accuracy in measuring the content of the polyethylene glycol in the compound polyethylene glycol electrolyte oral solution in the prior art are solved; the method is simple to operate, low in cost, high in speed and good in specificity and accuracy.

Description

Technical Field

[0001] The invention relates to the field of polyethylene glycol content detection methods, and in particular to a method for detecting the polyethylene glycol content in a composite polyethylene glycol electrolyte solution. Background Art

[0002] The main methods for detecting polyethylene glycol content include mass spectrometry, total organic carbon analysis, static light scattering, liquid chromatography and radioactivity analysis, among which liquid chromatography is the most commonly used. Liquid chromatography is used to determine the polyethylene glycol content using a differential detector, and the commonly used mobile phase is pure water (or an appropriate amount of antibacterial agent).

[0003] Compared with pure polyethylene glycol, the composition of compound polyethylene glycol (3350) electrolyte oral solution is more complex. When pure water (or adding an appropriate amount of antibacterial agent) is used as the mobile phase, it is found that the sodium and potassium ions in the compound polyethylene glycol (3350) electrolyte oral solution interfere with the chromatographic peak of polyethylene glycol (3350) (the interference amount is about 2.5%). The interference of sodium and potassium affects the specificity and accuracy of the determination of polyethylene glycol (3350) content. In order to solve the problem of sodium and potassium interference, the following methods can be used for optimization:

[0004] ① Treat the test sample to remove the sodium and potassium ions in the sample. Dialysis, ultrafiltration, solid phase extraction and other methods can be considered, but they have problems such as complex operation, high processing cost, long time consumption, and poor removal effect. In addition, our company tried dialysis, but it could not effectively improve the interference problem.

[0005] ② Optimize the chromatographic method to separate sodium and potassium ions from polyethylene glycol (3350). We were unable to separate the sodium and potassium peaks from polyethylene glycol (3350) by changing the column temperature, flow rate, detector temperature, etc.

[0006] In view of this, this application is filed. Summary of the invention

[0007] The object of the present invention is to provide a method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution, by optimizing the flow phase of liquid chromatography to separate potassium ions and / or sodium ions in polyethylene glycol, so as to solve the problem that sodium and potassium ions interfere with the accuracy of polyethylene glycol detection in the prior art.

[0008] The present invention is achieved through the following technical scheme: An embodiment of the present invention provides a method for detecting the content of polyethylene glycol in a compound polyethylene glycol electrolyte solution, the detection method adopts liquid chromatography, in the liquid chromatography, the mobile phase adopts an ethanol solution, and the ethanol solution is configured to separate potassium ions and / or sodium ions in the compound polyethylene glycol electrolyte solution from the polyethylene glycol.

[0009] Optionally, in the ethanol solution, the concentration of ethanol is 10-20 wt %.

[0010] Optionally, in the ethanol solution, the concentration of ethanol is 15 wt %.

[0011] Optionally, the molecular weight of the polyethylene glycol is greater than or equal to 1000.

[0012] Optionally, in the liquid chromatography method, the flow rate is 0.4 to 0.6 ml / min.

[0013] Optionally, in the liquid chromatography method, the column temperature is 30-40°C.

[0014] Optionally, in the liquid chromatography method, the differential detector temperature is 30-40°C.

[0015] Optionally, the liquid chromatography method includes any one of HPLC and GPC.

[0016] Optionally, the detection method uses HPLC detection, and the chromatographic conditions include using a hydrophilic polymer as a filler.

[0017] Optionally, in the chromatogram of the reference solution, the tailing factor of the polyethylene glycol peak is less than or equal to 2.0.

[0018] Compared with the prior art, the embodiments of the present invention have the following advantages and beneficial effects:

[0019] 1. The embodiment of the present invention changes the mobile phase in the chromatographic conditions, and replaces the existing mobile phase of pure water or adding an appropriate amount of antibacterial agent with an ethanol solution, so that polyethylene glycol is separated from sodium ions and potassium ions, thereby improving the problems of poor specificity and poor accuracy in determining the polyethylene glycol content in the compound polyethylene glycol electrolyte oral solution in the prior art. At the same time, the ethanol in the ethanol solution also has a bactericidal effect. The method is simple to operate, low in cost, fast in speed, and good in specificity and accuracy.

[0020] 2. By adopting the detection method of the embodiment of the present invention, linear regression was performed with polyethylene glycol concentration (mg / ml) as the abscissa and polyethylene glycol peak area as the ordinate. The linear equation was: y=25.7839x-0.8275, r was 0.9999 (>0.999), the response value of the y-axis intercept accounting for 100% was 1.6% (<2%), the residual sum of squares was 1.3, and the linear concentration range of polyethylene glycol was: 0.4194mg / ml~4.1938mg / ml, about 20%~200% level, and the linearity met the requirements.

[0021] 3. By adopting the detection method of the embodiment of the present invention, the average recovery rate is 99.9% (98% to 102%), the recovery rate RSD is 0.6% (<2%), and the accuracy range of polyethylene glycol is: 1.0346 mg / ml to 3.1623 mg / ml, about 50% to 150% level, and the accuracy meets the regulations.

[0022] 4. By adopting the detection method of the embodiment of the present invention, the system has high adaptability, the specificity meets the requirements, the detection results are stable, and the intermediate precision meets the requirements. The reference solution is placed at room temperature for 69 hours, and the peak area ratio of each point to 0h is in the range of 98% to 102%. The test solution is placed at room temperature for 51 hours, and the peak area ratio of each point to 0h is in the range of 98% to 102%. The reference solution is stable when placed at room temperature for 69 hours; the test solution is stable when placed at room temperature for 51 hours. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0024] Figure 1 It is a blank control chromatogram in the prior art;

[0025] Figure 2 It is a chromatogram showing the influence of potassium chloride and sodium chloride in the prior art;

[0026] Figure 3 It is a chromatogram of polyethylene glycol (3350) detection in the prior art;

[0027] Figure 4 A blank comparison chromatogram was provided for the study of the interference of polyethylene glycol (3350) in the prior art;

[0028] Figure 5 A comparative chromatogram of sucralose was studied for the interference of polyethylene glycol (3350) in the prior art;

[0029] Figure 6 The comparative chromatogram of banana flavor was studied for the interference of polyethylene glycol (3350) in the prior art;

[0030] Figure 7 A comparative chromatogram of diethylene glycol was studied for the interference of prior art polyethylene glycol (3350);

[0031] Figure 8 The ethylene glycol comparison chromatogram was studied for the interference of the prior art polyethylene glycol (3350);

[0032] Fig. 9 The comparison chromatograms of sodium chloride and potassium chloride are used to study the interference of polyethylene glycol (3350) of the present invention;

[0033] Fig.10 The detection chromatogram is a detection chromatogram in which the mobile phase of the prior art is replaced with a 0.02% potassium nitrate solution;

[0034] Fig.11 Detection of chromatograms under conditions of reduced flow rates for existing technologies;

[0035] Fig.12 The chromatogram is detected when the column temperature is increased in the prior art;

[0036] Fig.13 Detecting chromatograms while reducing the injection volume for existing technologies;

[0037] Fig.14 The chromatogram was detected in the case of the dialysis bag method for the prior art attempt;

[0038] Fig.15 Detection chromatogram under the condition of optimizing the mobile phase for the embodiment of the present invention;

[0039] Fig.16 This is a chromatogram for the system suitability verification test in Example 1 of the present invention;

[0040] Fig.17 This is a comparison chart showing that the specificity verification in Example 1 of the present invention is not damaged;

[0041] Fig.18 This is a comparison diagram of acid destruction for specificity verification in Example 1 of the present invention;

[0042] Fig.19 This is a comparison diagram of alkali damage for specificity verification in Example 1 of the present invention;

[0043] Fig. 20 This is a comparison diagram of oxidation damage for specificity verification in Example 1 of the present invention;

[0044] Fig.21 This is a high temperature damage comparison diagram for specific property verification in Example 1 of the present invention;

[0045] Fig. 22 This is a comparison diagram of light damage for specific property verification in Example 1 of the present invention;

[0046] Fig.23 This is the standard curve diagram in Example 1 of the present invention;

[0047] Fig.24 Graph showing the detection results for different molecular weights in the embodiments of the present invention;

[0048] Fig.25This is a test result diagram of Example 2 of the present invention;

[0049] Fig.26 This is a test result diagram of Example 3 of the present invention;

[0050] Fig. 27 This is a diagram of the detection results of Example 4 of the present invention. DETAILED DESCRIPTION

[0051] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Generally, the components of the embodiments of the present invention described and shown in the drawings here can be arranged and designed in various different configurations.

[0052] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0053] At present, the main detection methods of polyethylene glycol (3350) polymers include mass spectrometry, spectrophotometry, static light scattering, total organic carbon analysis, gel permeation chromatography (GPC) and radioactivity analysis, among which:

[0054] ① Mass spectrometry: good reproducibility, high sensitivity, rich fragment ion information and mature ion cleavage theory, but the molecular ion peak is weak or no molecular ion peak can be obtained, the sample needs to be heated and vaporized before ionization, the detection cost is higher than titration and chemical titration, the detection time is long, and the detection efficiency is low.

[0055] ②Static light scattering method: simple operation, good test results for monodisperse suspensions, but poor test results for polydisperse samples, low resolution, low detection efficiency, high experimental environment requirements, and cumbersome sample preparation

[0056] ③ Gel Permeation Chromatography: Compared with mass spectrometry and static scattering, gel permeation chromatography has the advantages of simple detection method, no need for special reagents, short detection time, and accurate detection results. It can be used to determine the content and molecular weight of polyethylene glycol (3350) in simple composition samples.

[0057] In the prior art, gel permeation chromatography (GPC) is used to detect the molecular weight and content of polyethylene glycol (3350). The commonly used chromatographic condition standards are derived from the standards for polyethylene glycol (4000) in Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0058] The existing technology includes setting the chromatographic conditions as mobile phase: 0.02% antibacterial agent; column temperature: 35°C; differential detector temperature: 35°C, flow rate 1.0ml / min, and acquisition time: 15min. The detection of polyethylene glycol (3350) under these conditions is as follows: Figure 1 and Figure 2 As shown by Figure 1 and Figure 2 It can be seen that when the mobile phase is set to 0.02% antibacterial agent, it is impossible to separate the polyethylene glycol 3350 and negative blank (sodium, potassium ion) chromatographic peaks. Therefore, this method is not suitable for the detection of polyethylene glycol (3350) content in the composite polyethylene glycol electrolyte solution in the embodiment of the present invention.

[0059] At the same time, the problem that sodium and potassium ions interfere with the polyethylene glycol chromatographic peak is an innovative problem of the embodiments of the present invention, specifically:

[0060] Table 1 is a comparison of USP polyethylene glycol (3350) and ChP polyethylene glycol (4000) methods during the research process.

[0061] Table 1

[0062]

[0063]

[0064] And using the tentative chromatographic conditions, the compound polyethylene glycol (3350) electrolyte oral solution was injected and analyzed. The chromatogram is as follows: Figure 3 As shown in the figure, a chromatographic peak appeared next to the main peak of polyethylene glycol (3350), which may affect the content and molecular weight detection. According to the analysis, the side chromatographic peak may be the peak of other components in the compound polyethylene glycol (3350) electrolyte oral solution in the system, interfering with the polyethylene glycol (3350) peak, so negative blank solution 1 (full prescription preparation without polyethylene glycol (3350)), banana flavor, ethylene glycol, diethylene glycol and sucralose were injected respectively. The results are shown in the figure below. Figures 4 to 8 As shown, it was found that in this system, banana flavor, ethylene glycol, diethylene glycol and sucralose did not interfere with polyethylene glycol (3350), and it may be that the other ingredients interfered with polyethylene glycol (3350).

[0065] Then inject sodium chloride and potassium chloride solutions and continue testing. The results are as follows. Fig. 9 As shown in the figure, it was found that sodium chloride and potassium chloride interfered with the specificity and accuracy of polyethylene glycol (3350). Therefore, in order to solve the interference problem of sodium chloride and potassium chloride, the following improvements and optimizations were made.

[0066] 1. Optimize chromatographic conditions

[0067] ①Change the mobile phase:

[0068] Chromatographic conditions

[0069] Mobile phase: 0.02% potassium nitrate solution; column temperature: 35°C; differential detector temperature: 35°C; flow rate: 1.0 ml / min; injection volume: 100 μl; acquisition time: 15 min.

[0070] The results of the chromatographic conditions are as follows Fig.10 As shown, it was found that the separation effect was still not achieved after the mobile phase was changed to 0.02% potassium nitrate solution.

[0071] ② Reduce flow rate:

[0072] Set the flow rate of the chromatographic conditions under item ① to 0.5 ml / min, the acquisition time to 30 min, and keep the other parameters unchanged, and then perform sample analysis.

[0073] The results are as follows Fig.11 As shown, it was found that after reducing the flow rate, the potassium chloride and sodium chloride peaks still interfered with the polyethylene glycol (3350) peak.

[0074] ③Increase column temperature:

[0075] Set the column temperature of the chromatographic condition under item ① to 45℃, and keep the other parameters unchanged. Fig.12 As shown, it was found that after increasing the column temperature, the potassium chloride and sodium chloride peaks still interfered with the polyethylene glycol (3350) peak.

[0076] ④Reduce the injection volume:

[0077] Chromatographic conditions: mobile phase: 0.02% antibacterial agent; column temperature: 35°C; differential detector temperature: 35°C; flow rate 1.0 ml / min; injection volume: 10 μl; acquisition time: 15 min. The injection analysis results are as follows Fig.13 As shown, it was found that after reducing the injection volume, the potassium chloride and sodium chloride peaks still interfered with the polyethylene glycol (3350) peak.

[0078] 2. Try the dialysis bag method

[0079] The compound polyethylene glycol electrolyte solution sample and blank excipient were dialyzed using a dialysis bag. The analysis results are as follows: Fig.14 As shown, it was found that after the sample was dialyzed, the interference of the auxiliary materials was not reduced, and the process of using dialysis bags to treat the samples was complicated and the processing time was long, so it was considered to optimize the mobile phase.

[0080] 3. Optimize the mobile phase

[0081] The mobile phase was adjusted to ethanol-water = 15:85. Considering the tolerance of the chromatographic column, the flow rate was reduced to 0.5 ml / min. Polyethylene glycol (3350) and various auxiliary material solutions were injected and analyzed. The results are as follows: Fig.15 As shown in the figure, it was found that under the chromatographic conditions, potassium chloride and sodium chloride did not produce peaks and did not interfere with the content detection of polyethylene glycol (3350). Therefore, after changing the mobile phase to ethanol solution, potassium chloride and sodium chloride did not interfere with polyethylene glycol (3350) and did not affect the specificity and accuracy of polyethylene glycol (3350).

[0082] Therefore, the present invention replaces the mobile phase with an ethanol solution to detect the composite polyethylene glycol electrolyte solution, and the detection method can be high performance liquid chromatography and gel permeation chromatography.

[0083] Example 1: A method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution is provided, and high performance liquid chromatography is used for detection. The specific detection conditions are:

[0084] Test solution: Take an appropriate amount of the product, weigh accurately, dissolve in water and quantitatively dilute to make a solution containing approximately 2.1 mg of polyethylene glycol 3350 per 1 ml;

[0085] Reference solution: Take an appropriate amount of polyethylene glycol (3350) reference substance, weigh accurately, dissolve in water and quantitatively dilute to make a solution containing about 2.1 mg per 1 ml;

[0086] Chromatographic conditions: Use hydrophilic polymer as filler (Target PolySEC-300 7.8×300mm, 5μm or chromatographic column with equivalent performance); ethanol-water (15:85) as mobile phase; flow rate is 0.5ml per minute, column temperature is 35℃, differential refractive index detector, detector temperature is 35℃; injection volume is 50μl;

[0087] System suitability requirements: In the chromatogram of the reference solution, the tailing factor of the polyethylene glycol 3350 peak should not exceed 2.0;

[0088] Determination method: Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph respectively, record the chromatogram, and calculate by peak area according to the external standard method.

[0089] Example 2: A method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution is provided. The difference from Example 1 is that the mobile phase component in the chromatographic conditions is ethanol-water (5:95), and the other conditions are the same. The detection results are as follows Fig.25 Said by Fig.25 It can be seen that when the ethanol concentration is less than 10%, the separation effect is not up to standard, and sodium chloride and potassium chloride still interfere.

[0090] Example 3: A method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution is provided. The difference from Example 1 is that the mobile phase component in the chromatographic conditions is ethanol-water (10:90), and the other conditions are the same. The detection results are as follows: Fig.26 As shown by Fig.26 It can be seen that when the ethanol concentration is equal to 10%, sodium chloride and potassium chloride no longer interfere.

[0091] Example 4: A method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution is provided. The difference from Example 1 is that the mobile phase component in the chromatographic conditions is ethanol-water (20:80), and the other conditions are the same. The detection results are as follows: Fig. 27 As shown by Fig. 27 It can be seen that when the ethanol concentration is equal to 20%, sodium chloride and potassium chloride no longer interfere. Polyethylene glycols with molecular weights of 600, 1000, 4000, 7000 and 10000 were tested according to the method of Example 1. The test results are as follows: Fig.24 As shown by Fig.24 It can be seen that the larger the molecular weight of polyethylene glycol is, the farther it is from the peaks of the positioning solution of sodium chloride and potassium chloride, and the better the detection effect is. When the molecular weight of polyethylene glycol is less than 1000, the separation effect is poor and the interference of sodium chloride and potassium chloride is large.

[0092] verify

[0093] The detection method of Example 1 was tested and verified, and the test contents included system suitability, specificity, linearity and range accuracy, precision (including repeatability and intermediate precision), solution stability and durability.

[0094] (1) System applicability

[0095] In this test, the solvent is water. The preparation process of reference solution A and B includes taking 21.31mg and 21.48mg of polyethylene glycol (3350) reference substance, accurately weighing, placing in different 10ml volumetric bottles, dissolving with solvent and diluting to scale, shaking well, and then obtaining. They are used as reference solution A and B respectively. The polyethylene glycol (3350) content is 2.1225mg / ml and 2.1394mg / ml respectively. Samples of solution A and B are injected respectively. The results are as follows Fig.16 As shown, Fig.16 The results after analysis are shown in Table 2:

[0096] Table 2

[0097]

[0098]

[0099] (2) Exclusivity

[0100] Since this product is a compound preparation, its main ingredients include sodium chloride, potassium chloride, sodium bicarbonate and polyethylene glycol (3350); the auxiliary material is sucralose; ethylene glycol, diethylene glycol and triethylene glycol are known impurities in polyethylene glycol (3350), so sodium chloride, potassium chloride, sodium bicarbonate, sucralose, ethylene glycol, diethylene glycol and triethylene glycol are selected as positioning solutions to examine the specificity.

[0101] First, prepare the solution. The preparation is shown in Table 3 below:

[0102] Table 3

[0103]

[0104]

[0105]

[0106] The above solutions were sampled and the test results are shown in Table 4 and Table 5. Figures 17 to 22 As shown, then Table 4, Table 5 and Figure 17-22 The results were compared with the acceptance criteria, and the results are shown in Table 6 below:

[0107] Table 4

[0108] Solution Retention time (min) Interference Undestroyed and various destroyed solvents / none Undamaged and damaged blank excipients dissolved / none Sodium chloride 18.150 / Potassium chloride 18.323 / Sodium bicarbonate / / Sucralose 31.673 / Ethylene glycol 19.413 / Diethylene glycol 18.977 / Triethylene glycol 18.527 / Polyethylene glycol 14.417 /

[0109] Table 5

[0110]

[0111] Table 6

[0112]

[0113]

[0114] (3) Linearity and range

[0115] First, the solution preparation is shown in Table 7 below:

[0116] Table 7

[0117]

[0118] The above solutions were sampled and the test results are shown in Table 8 below:

[0119] Table 8

[0120] name Concentration level Concentration (mg / ml) Peak area Linear 1 20％ 0.4194 9.948 Linear 2 50％ 1.0484 26.549 Linear 3 100％ 2.0969 52.575 Linear 4 150％ 3.1453 81.062 Linear 5 200％ 4.1938 106.971

[0121] The standard curve is as follows Fig.23 As shown, in Fig.23In the data, the linear equation is y=25.7839x-0.8275, the correlation coefficient r is 0.9999, the y-intercept accounts for 100% of the response value is 1.6%, and the residual sum of squares is 1.3.

[0122] Table 8 and Fig.23 The test results were compared with the acceptable standards, and the results are shown in Table 9 below:

[0123] Table 9

[0124]

[0125] (4) Accuracy

[0126] First, the solution was prepared. The preparation conditions are shown in Table 10 below:

[0127] Table 10

[0128]

[0129] Take samples of the above solutions respectively, record the data, and calculate using the following formula:

[0130]

[0131] Among them, W 对 : Weight of polyethylene glycol (3350) reference substance, mg;

[0132] P 对 : Content of polyethylene glycol (3350) reference substance, decimal form;

[0133] S 对 : Dilution multiple of polyethylene glycol reference substance, ml;

[0134] A 对 : Average peak area of ​​polyethylene glycol (3350) in reference solution; A 样 : Peak area of ​​polyethylene glycol (3350) in the test solution;

[0135] S 样 : Accuracy solution volume, ml;

[0136] S 贮 : Accuracy stock solution dilution volume, ml;

[0137] S 加 : Volume of accuracy stock solution added, ml.

[0138] The statistical results are shown in Table 11 below:

[0139] Table 11

[0140]

[0141] Comparison of the data in Table 11 with the acceptance criteria is shown in Table 12 below:

[0142] Table 12

[0143]

[0144] (5) Precision

[0145] 5.1 Repeatability

[0146] First, the solution is prepared, and the preparation is shown in Table 13 below:

[0147] Table 13

[0148]

[0149] The above solutions were sampled and the test results are shown in Table 14 below:

[0150] Table 14

[0151]

[0152] 5.2 Intermediate precision

[0153] For different dates, different personnel, and different instruments, the test was carried out under the repeatability item, and the solution preparation is shown in Table 15 below:

[0154] Table 15

[0155]

[0156] The above solutions were sampled and the test results are shown in Tables 16 and 17 below:

[0157] Table 16

[0158]

[0159] Table 17

[0160]

[0161] The test results of Tables 14, 16 and 17 were compared with the acceptable standards, and the results are shown in Table 18 below:

[0162] Table 18

[0163]

[0164]

[0165] (6) Solution stability

[0166] First, prepare the solution, and the preparation is shown in Table 19 below:

[0167] Table 19

[0168] name Preparation process Reference solution Same as reference solution A in Table 1. (Contains polyethylene glycol 3350 2.1225 mg / ml) Test solution Same as Table 13 for test solution 1.

[0169] Take the above solution, place it at room temperature for a certain period of time and then inject it. The test results are shown in Table 20 and Table 21 below:

[0170] Table 20

[0171]

[0172] Table 21

[0173]

[0174] Comparing the data in Tables 20 and 21 with the acceptable standards, the results are shown in Table 22 below:

[0175] Table 22

[0176]

[0177]

[0178] (7) Durability

[0179] Compared with normal conditions, the conditions in Table 23 below are changed in sequence:

[0180] Table 23

[0181]

[0182] First, the solution is prepared, and the preparation is shown in Table 24 below:

[0183] Table 24

[0184]

[0185] The above solutions were sampled and the test results are shown in Table 25 and Table 26 below:

[0186] Table 25

[0187]

[0188] The original conditions were flow rate 0.5 ml / min, column temperature 35°C, differential detector temperature 35°C, and mobile phase ethanol-water (15:85).

[0189] Table 26

[0190]

[0191] Comparing Table 25 and Table 26 with the acceptable standards, the comparison is shown in Table 27 below:

[0192] Table 27

[0193]

[0194]

[0195] It can be seen that according to the ChP 9101 analytical method validation guidelines, the system suitability and specificity, linearity and range, accuracy, precision (repeatability and intermediate precision), solution stability and durability of the polyethylene glycol (3350) content in the compound polyethylene glycol (3350) electrolyte oral solution were tested, and all validation items met the acceptable standards.

[0196] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method of the present invention and is not intended to limit the scope of protection of the present invention. 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 detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution, the method using liquid chromatography, characterized in that: In the liquid chromatography method, the mobile phase is an ethanol solution, and the ethanol solution is configured to separate the potassium ions and / or sodium ions in the composite polyethylene glycol electrolyte solution from the polyethylene glycol.

2. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 1, characterized in that: In the ethanol solution, the concentration of ethanol is 10-20 wt%.

3. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 2, characterized in that: In the ethanol solution, the concentration of ethanol is 15 wt %.

4. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to any one of claims 1 to 3, characterized in that: The molecular weight of the polyethylene glycol is greater than or equal to 1000.

5. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 2, characterized in that: In the liquid chromatography method, the flow rate is 0.4 to 0.6 ml / min.

6. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 5, characterized in that: In the liquid chromatography method, the column temperature is 30 to 40°C.

7. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 6, characterized in that: In the liquid chromatography, the differential detector temperature is 30 to 40°C.

8. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 1, characterized in that: The liquid chromatography method includes any one of HPLC and GPC.

9. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 8, characterized in that: The detection method adopts HPLC detection, and the chromatographic conditions include adopting a hydrophilic polymer as a filler.

10. The method for detecting the content of polyethylene glycol in a composite polyethylene glycol electrolyte solution according to claim 9, characterized in that: In the chromatogram of the reference solution, the tailing factor of the polyethylene glycol peak is less than or equal to 2.0.

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