Method for measuring K value of polyvinylpyrrolidone

Abstract

The invention discloses a method for determining the K value of polyvinylpyrrolidone, and relates to the technical field of high polymer material determination. Based on the principle of molecular exclusion chromatography, the K value of PVP is judged by detecting the retention time of a to-be-detected sample and a reference substance by utilizing a molecular sieving mechanism of a gel chromatographic column; the method comprises the steps of preparation of a sample and a reference substance solution, operation setting of a high performance liquid chromatograph and analysis of detection data. Compared with a traditional Ubbelohde capillary viscometer method, the method has the advantages of being small in sample dosage, high in detection precision, good in reproducibility and easy and convenient to operate, the testing efficiency can be remarkably improved, and experimental errors can be reduced.

Description

Technical Field

[0001] The invention relates to the technical field of polymer material determination, in particular to a method for determining the K value of polyvinyl pyrrolidone. Background Art

[0002] The traditional method for determining the K value of polyvinyl pyrrolidone usually uses an Ubbelohde capillary viscometer; this method measures the outflow time of the sample to be tested and purified water in the viscometer, and then uses a formula to calculate the K value of PVP; however, this method has some significant disadvantages, including high sample consumption, long test time, poor reproducibility, and susceptibility to human operating errors; this limits the reliability of this method in practical applications, especially in situations where high-precision and high-repeatability testing is required.

[0003] Based on this, a method for determining the K value of polyvinyl pyrrolidone is needed. Summary of the invention

[0004] To achieve the above object, the present invention provides the following scheme: a method for determining the K value of polyvinyl pyrrolidone, comprising the following steps: Step 1: Prepare a solution of the polyvinyl pyrrolidone (PVP) sample to be tested. Take 0.8 to 1.2 ml of the sample to be tested, add pure water and dilute to 8 to 12 ml, shake well to obtain a solution of the sample to be tested. As a reference standard, dissolve an appropriate amount of the reference substance in water to prepare a reference substance solution with a concentration of 0.5 to 0.7 mg / ml. Step 2: After the sample is prepared, use Waters e2695 high performance liquid chromatograph and Waters 2414 differential refractometer. The chromatographic column uses Tosoh TSKgel G4000PWXL, the pore size of which should match the molecular weight range of the sample. Set the column temperature to 35°C to 45°C, the detector temperature to 30°C to 40°C, and use 0.1 to 0.3 mol / L sodium nitrate aqueous solution as the mobile phase, and control the flow rate to 0.3 to 0.5 ml / min. Step 3. After the instrument is prepared, 15 to 25 microliters of the pre-prepared reference solution and the sample solution to be tested are injected into the high performance liquid chromatograph for separation and detection. Using the separation principle of molecular exclusion chromatography, the molecules in the sample will be selectively screened according to their size when passing through the chromatographic column. The chromatographic column is filled with pores of different sizes. When molecules larger than all pores cannot enter the pores of the filler, the molecules will quickly pass through the chromatographic column and will not be retained, which is manifested as a short retention time of 10 to 15 minutes. On the contrary, molecules with small molecular weight can freely enter all pores of the filler, so the time they stay in the chromatographic column is manifested as a retention time of 20 to 30 minutes. For molecules with molecular sizes between large and small molecules, they will be partially screened and eluted in turn according to their size, and the retention time is between 15 and 20 minutes. Step 4: Record the retention time of the sample by a differential refractometer and compare it with the retention time of the reference solution. If the retention time of the sample is consistent with that of the reference within the allowable error range, then their K values ​​are judged to be the same; if the retention times are different, the K value is estimated based on the difference in retention times.

[0005] Further preferably, the chromatographic column uses gel fillers with different pore size ranges to adapt to the detection of PVP with different molecular weight ranges. The pore size range of the chromatographic column is selected according to the molecular weight of the sample to be tested, so that high molecular weight PVP samples are not retained by the filler, while low molecular weight PVP samples can be screened by the filler.

[0006] Further preferably, the mobile phase is a 0.2 mol / L sodium nitrate aqueous solution, and is filtered to remove particles or bubbles. The mobile phase is prepared with high-purity sodium nitrate and deionized water, and is filtered through a 0.45 micron filter membrane before use.

[0007] Further preferably, the reference substance is povidone K15 or K30, and an appropriate reference substance is selected according to the molecular weight of the sample to be tested. The reference substance is prepared as a solution according to the sample preparation steps before analysis.

[0008] Further preferably, the signal detection sensitivity of the differential refractometer detector is set to be above 95%, and the differential refractometer detector is used to detect the refractive index signal of the sample and is adjusted to the sensitivity range.

[0009] Further preferably, the determination method includes estimating the K value based on a fitting curve of retention time and molecular weight, wherein the fitting curve is established through a curve of relationship between the retention time of the sample and the molecular weight of the standard sample.

[0010] Further preferably, the determination method is applicable to the molecular weight analysis of high molecular weight polymers such as polyvinyl alcohol and carboxymethyl cellulose, and the molecular weight analysis of the high molecular weight polymer only requires adjustment of the reference substance, the pore size range of the chromatographic column and the composition of the mobile phase.

[0011] Further preferably, the column temperature range of the chromatographic column is 35° C. to 45° C., the detector temperature range is 30° C. to 40° C., and the flow rate is 0.3 to 0.5 ml / min.

[0012] According to the specific embodiments provided by the present invention, the present invention discloses the following technical effects: This method utilizes molecular sieving in a gel chromatographic column to separate PVP samples of different molecular sizes. PVP molecules enter the pores of the gel filler in the chromatographic column according to their size. Larger molecules cannot enter the pores and will be eluted faster, showing a shorter retention time; small molecules can penetrate deep into the filler pores, thus retaining a longer time; by recording the retention time of the sample to be tested and a reference substance with a known K value, and performing comparative analysis, the K value of the sample to be tested can be accurately determined; compared with the traditional Ubbelohde capillary viscometer determination method, this method requires less sample and reduces the experimental cost; secondly, the determination process is fast and has high accuracy and good reproducibility, reducing the influence of human errors, and is relatively simple to operate, making it suitable for routine laboratory analysis and large-scale sample screening. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0014] Figure 1 It is a flow chart of the steps of the present invention. DETAILED DESCRIPTION

[0015] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments 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 creative work are within the scope of protection of the present invention.

[0016] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0017] Example 1 like Figure 1 As shown, a method for determining the K value of polyvinyl pyrrolidone in this embodiment comprises the following steps: Step 1: Prepare a solution of the polyvinyl pyrrolidone (PVP) sample to be tested. Take 0.9 ml of the sample to be tested, add pure water and dilute to 9 ml, shake well to obtain the sample solution to be tested; as a reference standard, select povidone K15 as a reference substance, dissolve an appropriate amount of the reference substance in water, and prepare a reference substance solution with a concentration of 0.6 mg / ml to adapt to the detection of PVP in the low molecular weight range; Step 2: After the sample preparation is completed, use Waters e2695 high performance liquid chromatograph and Waters 2414 differential refractometer. The chromatographic column is Tosoh TSKgel G4000PWXL, whose pore size is suitable for the separation of low molecular weight samples. The column temperature is set to 36°C, the detector temperature is set to 31°C, and a 0.2 mol / L sodium nitrate aqueous solution is used as the mobile phase. The mobile phase is prepared with high-purity sodium nitrate and deionized water and filtered through a 0.45 micron filter membrane to remove particles or bubbles. The flow rate is controlled at 0.4 ml / min. Step 3: After the instrument is prepared, 20 microliters of the pre-prepared reference solution and the sample solution to be tested are injected into the high performance liquid chromatograph for separation and detection; the separation principle of molecular exclusion chromatography is used to selectively screen the molecules in the sample according to their size when passing through the chromatographic column; the chromatographic column is filled with pores of different sizes. When molecules larger than all pores cannot enter the pores of the filler, the molecules will quickly pass through the chromatographic column, which is manifested as a short retention time of about 12 minutes; small molecular weight molecules enter all pores of the filler and stay for about 28 minutes; for molecules between these two, the retention time is about 17 minutes; during the detection process, the sensitivity of the differential refractometer is adjusted to 97% to ensure stable detection of the signal; Step 4: Record the retention time of the sample by a differential refractometer and compare it with the retention time of the reference solution; if the retention time of the sample is consistent with that of the reference within ±0.1 minutes, then it is determined that their K values ​​are the same; if the retention times are different, the K value is calculated based on the difference in retention times; during the calculation process, a linear fitting curve of the sample retention time and the molecular weight of the standard sample is established, and the K value of the sample to be tested is calculated based on the fitting curve; Example 2 The difference from Example 1 is that a method for determining the PVPK value of polyvinyl pyrrolidone comprises the following steps: Step 1: Prepare a solution of the polyvinyl pyrrolidone (PVP) sample to be tested. Take 1.1 ml of the sample to be tested, add pure water and dilute to 10 ml, shake well to obtain the sample solution to be tested; as a reference standard, select povidone K30 as a reference substance, dissolve an appropriate amount of the reference substance in water, and prepare a reference substance solution with a concentration of 0.7 mg / ml to adapt to the detection of PVP in the medium molecular weight range; Step 2: After the sample preparation is completed, use Waters e2695 high performance liquid chromatograph and Waters 2414 differential refractometer. The chromatographic column is Tosoh TSKgel G4000PWXL, whose pore size is suitable for the separation of medium molecular weight samples. The column temperature is set to 40°C, the detector temperature is set to 35°C, and 0.25 mol / L sodium nitrate aqueous solution is used as the mobile phase. The mobile phase is filtered through a 0.45 micron filter membrane to remove particles or bubbles. The flow rate is controlled at 0.35 ml / min. Step 3: After the instrument is prepared, 18 microliters of the pre-prepared reference solution and the sample solution to be tested are injected into the high performance liquid chromatograph for separation and detection; the separation principle of molecular exclusion chromatography is used to selectively screen the molecules in the sample according to their size when passing through the chromatographic column; the chromatographic column is filled with pores of different sizes. When molecules larger than all pores cannot enter the pores of the filler, the molecules will quickly pass through the chromatographic column, which is manifested as a short retention time of about 11 minutes; small molecular weight molecules enter all pores of the filler and stay for about 26 minutes; for molecules between these two, the retention time is about 18 minutes; during the detection process, the sensitivity of the differential refractometer is adjusted to 96%; Step 4: Record the retention time of the sample by a differential refractometer and compare it with the retention time of the reference solution; if the retention time of the sample is consistent with that of the reference within ±0.2 minutes, then it is determined that their K values ​​are the same; if the retention times are different, the K value is estimated based on the difference in retention times; during the estimation process, a polynomial fitting curve of the sample retention time and the molecular weight of the standard sample is established; Example 3 The difference from Example 2 is that a method for determining the PVPK value of polyvinyl pyrrolidone comprises the following steps: Step 1: Prepare a solution of the polyvinyl pyrrolidone (PVP) sample to be tested. Take 1.0 ml of the sample to be tested, add pure water and dilute to 11 ml, shake well to obtain the sample solution to be tested; as a reference standard, select povidone K30 as a reference substance, dissolve an appropriate amount of the reference substance in water, and prepare a reference substance solution with a concentration of 0.55 mg / ml to adapt to the detection of PVP in the medium to high molecular weight range; Step 2: After the sample preparation is completed, use Waters e2695 high performance liquid chromatograph and Waters 2414 differential refractometer. The chromatographic column is Tosoh TSKgel G4000PWXL, whose pore size is suitable for the separation of high molecular weight samples. The column temperature is set to 38°C, the detector temperature is set to 32°C, and 0.15 mol / L sodium nitrate aqueous solution is used as the mobile phase. The mobile phase is filtered through a 0.45 micron filter membrane to remove particles or bubbles. The flow rate is controlled at 0.3 ml / min. Step 3: After the instrument is prepared, inject 22 microliters of the pre-prepared reference solution and the sample solution to be tested into the high performance liquid chromatograph for separation and detection; using the separation principle of molecular exclusion chromatography, the molecules in the sample are selectively screened according to their size when passing through the chromatographic column; the chromatographic column is filled with pores of different sizes. When molecules larger than all pores cannot enter the pores of the filler, the molecules will quickly pass through the chromatographic column, which is manifested as a short retention time of about 14 minutes; small molecular weight molecules enter all pores of the filler and stay for about 24 minutes; for molecules between these two, the retention time is about 19 minutes; during the detection process, adjust the sensitivity of the differential refractometer to 95%; Step 4: Record the retention time of the sample by a differential refractometer and compare it with the retention time of the reference solution; if the retention time of the sample is consistent with that of the reference within ±0.15 minutes, then their K values ​​are judged to be the same; if the retention times are different, calculate the K value based on the difference in retention times; during the calculation process, establish a logarithmic fitting curve between the sample retention time and the molecular weight of the standard sample.

[0018] The following are experimental conditions and test result tables of three examples, which are used to illustrate the K value determination process of polyvinylpyrrolidone PVP under different samples and test conditions;

[0019] Example 1 is suitable for low molecular weight PVP samples. By selecting povidone K15 as a reference substance, a good separation effect is ensured in low molecular weight detection. The column temperature is set to 36°C, the detector temperature is set to 31°C, and a 0.2 mol / L sodium nitrate aqueous solution is used as the mobile phase. These conditions ensure that molecules with lower molecular weight can effectively enter the filler pore size for screening, while maintaining a high sensitivity (97%), so that the retention time difference is significant and the detection accuracy is high, which is suitable for accurate K value calculation. The test results show that the retention time of short molecules is about 12 minutes, and the retention time of long molecules is 28 minutes. The K value is calculated by linear fitting, which reduces the error of the measurement; Example 2 For PVP samples in the medium molecular weight range, povidone K30 was used as a reference substance, and the column temperature was set to 40°C and the detector temperature was set to 35°C, and a 0.25 mol / L sodium nitrate aqueous solution was used as the mobile phase, and the flow rate was set to 0.35 ml / min; this setting enables the medium molecular weight PVP sample to achieve moderate screening and ensure stable signal detection (sensitivity 96%); the retention time range is from 11 minutes (short) to 26 minutes (long), which is suitable for polynomial fitting curves to calculate K values, which can improve the fitting accuracy and is particularly suitable for the analysis of medium molecular weight samples; Example 3 is used to detect medium to high molecular weight PVP samples. A lower concentration of povidone K30 (0.55 mg / ml) is selected as a reference substance. The column temperature is set to 38°C, the detector temperature is set to 32°C, and the mobile phase concentration is reduced to 0.15 mol / L to adapt to the screening and detection of high molecular weight samples. A lower flow rate (0.3 ml / min) and moderate temperature conditions ensure a longer screening process, so that the retention time can reach 14 minutes (short) to 24 minutes (long). The detector sensitivity is set to 95% to balance the accuracy of signal capture. The logarithmic fitting method is used to calculate the K value, which is suitable for processing samples with a wide molecular weight distribution.

[0020] By optimizing the experimental conditions and determination methods of different embodiments, suitable detection parameters are selected for PVP samples in different molecular weight ranges to achieve high-precision calculation of K values. Each embodiment adjusts the settings of chromatographic column temperature, detector temperature, mobile phase concentration and flow rate to match the screening requirements of different molecular weights, ensure the determination accuracy of retention time, and calculate K values ​​through appropriate fitting methods (linear fitting, polynomial fitting, logarithmic fitting) to improve the accuracy of detection.

[0021] The technical features of the above embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0022] The principles and implementation methods of the present invention are described in this article using specific examples. The description of the above embodiments is only used to help understand the method and core idea of ​​the present invention. At the same time, for those skilled in the art, according to the idea of ​​the present invention, there will be changes in the specific implementation methods and application scope. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. A method for determining the K value of polyvinyl pyrrolidone, characterized in that: The following steps are involved: Step 1: Prepare a solution of the polyvinyl pyrrolidone (PVP) sample to be tested. Take 0.8 to 1.2 ml of the sample to be tested, add pure water and dilute to 8 to 12 ml, shake well to obtain a solution of the sample to be tested. As a reference standard, dissolve an appropriate amount of the reference substance in water to prepare a reference substance solution with a concentration of 0.5 to 0.7 mg / ml. Step 2: After the sample is prepared, use Waters e2695 high performance liquid chromatograph and Waters 2414 differential refractometer. The chromatographic column uses Tosoh TSKgel G4000PWXL, the pore size of which should match the molecular weight range of the sample. Set the column temperature to 35°C to 45°C, the detector temperature to 30°C to 40°C, and use 0.1 to 0.3 mol / L sodium nitrate aqueous solution as the mobile phase, and control the flow rate to 0.3 to 0.5 ml / min. Step 3. After the instrument is prepared, 15 to 25 microliters of the pre-prepared reference solution and the sample solution to be tested are injected into the high performance liquid chromatograph for separation and detection. Using the separation principle of molecular exclusion chromatography, the molecules in the sample will be selectively screened according to their size when passing through the chromatographic column. The chromatographic column is filled with pores of different sizes. When molecules larger than all pores cannot enter the pores of the filler, the molecules will quickly pass through the chromatographic column and will not be retained, which is manifested as a short retention time of 10 to 15 minutes. On the contrary, molecules with small molecular weight can freely enter all pores of the filler, so the time they stay in the chromatographic column is manifested as a retention time of 20 to 30 minutes. For molecules with molecular sizes between large and small molecules, they will be partially screened and eluted in turn according to their size, and the retention time is between 15 and 20 minutes. Step 4: Record the retention time of the sample by a differential refractometer and compare it with the retention time of the reference solution. If the retention time of the sample is consistent with that of the reference solution within the allowable error range, then it is determined that their K values ​​are the same; If the retention times are different, the K value is estimated based on the difference in retention times.

2. The method for determining the K value of polyvinyl pyrrolidone according to claim 1, wherein: The chromatographic column uses gel fillers with different pore size ranges to adapt to the detection of PVP with different molecular weight ranges. The pore size range of the chromatographic column is selected according to the molecular weight of the sample to be tested, so that high molecular weight PVP samples are not retained by the filler, while low molecular weight PVP samples can be screened by the filler.

3. The method for determining the K value of polyvinyl pyrrolidone according to claim 1, characterized in that: The mobile phase is a 0.2 mol / L sodium nitrate aqueous solution, and is filtered to remove particles or bubbles. The mobile phase is prepared with high-purity sodium nitrate and deionized water, and is filtered through a 0.45 micron filter membrane before use.

4. The method for determining the K value of polyvinyl pyrrolidone according to claim 1, wherein: The reference substance is povidone K15 or K30. An appropriate reference substance is selected according to the molecular weight of the sample to be tested. The reference substance is prepared as a solution according to the sample preparation steps before analysis.

5. The method for determining the K value of polyvinyl pyrrolidone according to claim 1, characterized in that: The signal detection sensitivity of the differential refractive index detector is set to be above 95%. The differential refractive index detector is used to detect the refractive index signal of the sample and is adjusted to the sensitivity range.

6. The method for determining the K value of polyvinyl pyrrolidone according to claim 1, characterized in that: The determination method comprises calculating the K value according to a fitting curve of retention time and molecular weight, wherein the fitting curve is established through a curve of relationship between the retention time of the sample and the molecular weight of the standard sample.

7. The method for determining the K value of polyvinyl pyrrolidone according to claim 1, characterized in that: The determination method is applicable to the molecular weight analysis of high molecular weight polymers such as polyvinyl alcohol and carboxymethyl cellulose, and the molecular weight analysis of the high molecular weight polymer only requires adjustment of the reference substance, the pore size range of the chromatographic column and the composition of the mobile phase.

8. The method for determining the K value of polyvinyl pyrrolidone according to claim 1, characterized in that: The column temperature range of the chromatographic column is 35° C. to 45° C., the detector temperature range is 30° C. to 40° C., and the flow rate is 0.3 to 0.5 ml / min.

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