A detection method for formic acid in povidone K90

Abstract

The present invention relates to the field of detection of pharmaceutical excipients, and discloses a method for detecting formic acid in povidone K90, which includes the preparation steps of a test solution, the preparation steps of a reference solution, and the detection steps. In the preparation steps of the test solution, after diluting the povidone K90 sample, it is passed through a strongly acidic ion exchange resin layer, and the effluent is collected as the test solution. In the pretreatment process of the sample in the present invention, the use of a strongly acidic ion exchange resin layer for pretreatment can, firstly, purify the sample and reduce the interference of impurity peaks, and secondly, enable the sample solution to be better detected in a chromatographic column filled with a strongly acidic ion exchange resin. During the detection process by high performance liquid chromatography, the use of a chromatographic column filled with a strongly acidic ion exchange resin can make the tailing of the formic acid peak in the povidone K90 sample and the separation from the impurity peaks meet the requirements of chromatography; and this method has broad applicability and is applicable to the detection of formic acid in both povidone K25 and povidone K30 at the same time.

Description

Technical Field

[0001] The present invention relates to the field of detection of pharmaceutical excipients, and particularly to a method for detecting formic acid in povidone K90. Background Art

[0002] As one of the commonly used pharmaceutical excipients, povidone K90 is often used as a binder, solubilizer, etc. in pharmaceuticals. Formic acid has acute toxicity, irritation, subacute and chronic toxicity, and its content needs to be controlled in pharmaceutical excipients. Therefore, it is very necessary to detect formic acid.

[0003] In the prior art, the method for determining formic acid in povidone is to refer to the "Chinese Pharmacopoeia", directly add mobile phase, use octadecylsilane-bonded silica gel as the filler for detection, inject it into the liquid chromatograph, record the chromatogram, and calculate according to the external standard method with the peak area, not exceeding 0.5%. Povidone series products are homopolymers of 1-vinyl-2-pyrrolidone obtained by polymerizing pyrrolidone and acetylene under pressure to form vinylpyrrolidone monomers and polymerizing under the action of a catalyst. Due to different degrees of polymerization, the molecular weights of the polymers are also different. Under the mainstream detection method, although povidone K30 can be effectively detected, the formic acid peak of povidone K90 products has obvious tailing under this method, cannot be separated from other peaks in the sample, and the measurement result has a large error. Summary of the Invention

[0004] The present invention aims to provide a method for detecting formic acid in povidone K90 to solve the problem that formic acid in povidone K90 products cannot be effectively detected, resulting in a large error in the measurement result.

[0005] To achieve the above object, the present invention adopts the following technical scheme: A method for detecting formic acid in povidone K90, including the preparation steps of the test solution, the preparation steps of the reference solution, and the detection steps. In the preparation steps of the test solution, after diluting the povidone K90 sample, pass it through a strongly acidic ion exchange resin layer, and collect the effluent as the test solution.

[0006] Preferably, as an improvement, in the preparation steps of the test solution, the inner diameter of the filling of the strongly acidic ion exchange resin layer is 0.8 cm, the filling height is 20 mm, and the strongly acidic ion exchange resin layer is always immersed in water.

[0007] Preferably, as an improvement, before the povidone K90 sample passes through the strongly acidic ion exchange resin layer, first add 5 ml of water and adjust the flow rate to 1 ml / min.

[0008] Preferably, as an improvement, when the povidone K90 sample passes through the strongly acidic ion exchange resin layer, discard the first 2 ml of the effluent, and then collect 1.5 mL of the effluent as the test solution.

[0009] Preferably, as an improvement, in the preparation step of the reference solution, the concentration of the formic acid reference solution is 10 μg / ml.

[0010] Preferably, as an improvement, in the detection step, high performance liquid chromatography is used for detection.

[0011] Preferably, as an improvement, during high performance liquid chromatography detection, a strongly acidic ion exchange resin is used as the packing material, perchloric acid - water is used as the mobile phase, and the volume ratio of perchlorate to water is 1:699.

[0012] Preferably, as an improvement, during high performance liquid chromatography detection, the chromatographic conditions are: the detection wavelength is 210 nm, the chromatographic column is the ion exchange column Hi - plex H, and the injection volume is 50 μl.

[0013] The principle and beneficial effects of this technical solution are as follows:

[0014] 1. During the pretreatment process of the sample in this technical solution, a strongly acidic ion exchange resin layer is used for pretreatment. Firstly, it can purify the sample and reduce the interference of impurity peaks. Secondly, it enables the sample solution to be better detected in the chromatographic column packed with a strongly acidic ion exchange resin.

[0015] 2. During the detection process of this technical solution using high performance liquid chromatography, the chromatographic column packed with a strongly acidic ion exchange resin can make the tailing of the formic acid peak in the povidone K90 sample and the separation from impurity peaks meet the chromatographic requirements.

[0016] 3. The method for detecting formic acid in povidone K90 provided in this technical solution is also applicable to the detection of formic acid in povidone K25 and povidone K30. Compared with the mainstream detection methods, it has a wider applicability. Description of the Drawings

[0017] Figure 1 is the chromatogram of formic acid detection in povidone K90 in Example 1 of the present invention;

[0018] Figure 2 is the chromatogram of formic acid reference substance determination in Example 1 of the present invention;

[0019] Figure 3 is the chromatogram of formic acid detection in povidone K25 in Example 2 of the present invention;

[0020] Figure 4 is the chromatogram of formic acid detection in povidone K90 in Comparative Example 1 of the present invention;

[0021] Figure 5 is the chromatogram of formic acid reference substance determination in Comparative Example 1 of the present invention;

[0022] Figure 6It is the chromatogram of formic acid detection in povidone K90 of Comparative Example 2 of the present invention;

[0023] Figure 7 It is the chromatogram of formic acid detection in povidone K25 of Comparative Example 3 of the present invention. Specific embodiments

[0024] The following is a further detailed description through specific embodiments, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following embodiments are conventional means well-known to those skilled in the art; the experimental methods used are all conventional methods; the materials, reagents, etc. used can all be obtained from commercial sources.

[0025] General description of the solution:

[0026] A method for detecting formic acid in povidone K90 includes the following steps:

[0027] Step 1. Preparation of the test solution: Take 2.0 g of the sample (calculated as anhydrous substance), accurately weigh it, place it in a 100 ml volumetric flask, dissolve it with water and dilute to the mark, shake well, and use it as the test stock solution. Transfer the strong acidic ion exchange resin suspension to a glass column with an inner diameter of 0.8 cm, with a packing length of 20 mm, and keep the strong acidic ion exchange resin layer immersed in water all the time. Add 5 ml of water and adjust the flow rate to about 1 ml / min. When the liquid level drops to near the top of the strong acidic ion exchange resin layer, add the test stock solution into the column, discard the first 2 ml of the effluent, and then collect 1.5 mL of the solution as the test solution.

[0028] Step 2. Preparation of the reference solution: Take an appropriate amount of formic acid reference substance, accurately weigh it, dissolve it with water and dilute to make a solution containing 10 μg per 1 ml as the reference solution.

[0029] Step 3. Detection: Determine according to the high performance liquid chromatography method (General Rule 0512), using strong acidic ion exchange resin as the filler, perchloric acid - water (1:699) as the mobile phase, and the detection wavelength is 210 nm. The resolution between formic acid and adjacent peaks in the test solution should meet the requirements. Accurately measure 50 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph, record the chromatogram, and calculate by the external standard method based on the peak area.

[0030] Example 1

[0031] A method for detecting formic acid in povidone K90, which uses high performance liquid chromatography to determine the content of formic acid, includes the following steps:

[0032] Step 1. Preparation of the test solution: Take 2.0 g of povidone K90 (calculated as anhydrous substance), accurately weigh it, place it in a 100-ml volumetric flask, dissolve it with water and dilute to the mark, shake well to obtain the test stock solution. Transfer the strongly acidic ion exchange resin suspension to a glass column with an inner diameter of 0.8 cm, fill it to a length of 20 mm, and keep the strongly acidic ion exchange resin layer immersed in water all the time. Add 5 ml of water to the glass column, adjust the flow rate to 1 ml / min. When the liquid level drops to near the top of the strongly acidic ion exchange resin layer, add the test stock solution into the column, discard the first 2 ml of the effluent, and then collect 1.5 mL of the solution as the test solution.

[0033] Step 2. Preparation of the reference solution: Take an appropriate amount of formic acid reference substance, accurately weigh it, dissolve it with water and dilute to make a solution containing 10 μg per 1 ml as the reference solution.

[0034] Step 3. Detection: Perform detection by high performance liquid chromatography. Accurately measure 50 μl each of the reference solution and the test solution, and inject them into the liquid chromatograph respectively. Use an ion exchange column Hi-plex H (300×7.7 mm, 8 μm), use perchloric acid-water (1:699) as the mobile phase, the detection wavelength is 210 nm, and calculate according to the external standard method with the peak area. Record the chromatogram, and the results are as Figure 1 、 Figure 2 shown, among which, Figure 1 is the chromatogram of formic acid detection in povidone K90, Figure 2 is the chromatogram of formic acid reference substance determination.

[0035] Example 2

[0036] The difference between Example 2 and Example 1 is that: the test substance is replaced from povidone K90 with povidone K25, record the chromatogram, as Figure 3 shown.

[0037] Comparative Example 1

[0038] The difference between this comparative example and Example 1 is that: the ion exchange column Hi-plex H (300×7.7 mm, 8 μm) is replaced with a chromatographic column ZORBAX-SB-C18 (4.6×250 mm, 5 μm), record the chromatogram, as Figure 4 、 Figure 5 shown. Among them Figure 4 is the chromatogram of formic acid detection in povidone K90 (the same batch product as in Example 1); Figure 5 is the chromatogram of formic acid reference substance determination, the resolution of the sample does not meet the requirements, and the peak shape is poor.

[0039] Comparative Example 2

[0040] The difference between this comparative example and Example 1 is that the ion exchange column Hi-plex H (300×7.7 mm, 8 μm) was replaced with a chromatographic column AQ-C18 (4.6×250 mm, 5 μm), and the detection chromatogram of formic acid in povidone K90 (the same batch product as in Example 1) was recorded. As Figure 6 shown. It can be seen from Figure 6 that the formic acid peak is difficult to separate from other substance peaks, and the resolution does not meet the requirements.

[0041] Comparative Example 3

[0042] The difference between this comparative example and Example 1 is that the ion exchange column Hi-plex H (300×7.7 mm, 8 μm) was replaced with a chromatographic column ZORBAX-SB-C18 (4.6×250 mm, 5 μm), and the detection chromatogram of formic acid in povidone K25 was recorded. As Figure 7 shown.

[0043] In summary, according to Figures 1-3 it can be known that when using the ion exchange column Hi-plex H (300×7.7 mm, 8 μm), the resolution of the samples povidone K90 and povidone K25 and the resolution and peak shape of the formic acid reference substance are all good, the difference in the retention time of formic acid measured is small, and the formic acid content in povidone K90 and povidone K30 can be accurately detected.

[0044] It can be seen from Figure 4 , Figure 5 , Figure 7 that when using the chromatographic column ZORBAX-SB-C18 (4.6×250 mm, 5 μm), the resolution between the formic acid peak and other peaks in povidone K90 does not meet the requirements, the peak shape is poor, the formic acid peak in the formic acid reference substance is just separated from other peaks, and the formic acid in povidone K25 cannot be separated and the peak shape is poor, indicating that using the chromatographic column ZORBAX-SB-C18 (4.6×250 mm, 5 μm) is not applicable to the detection of formic acid in povidone K90 and K25 samples. And it can be seen from Figure 6 that when using the chromatographic column AQ-C18 (4.6×250 mm, 5 μm), the resolution between the formic acid peak and other peaks in povidone K90 also does not meet the requirements, and the peak shape is poor.

[0045] By comparing Figure 1 , Figure 4 and Figure 6 it can be known that when using different chromatographic columns to detect formic acid in the same batch of povidone K90, using the ion exchange column Hi-plex H (300×7.7 mm, 8 μm) can obtain better resolution and peak shape.

[0046] The above are only embodiments of the present invention, and common general technical solutions and / or characteristics in the solutions are not described in detail herein. It should be noted that for those skilled in the art, without departing from the technical solution of the present invention, several deformations and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the implementation effect of the present invention and the practicability of the patent. The protection scope claimed in this application shall be subject to the content of its claims, and the specific implementation manners and the like recorded in the specification can be used to interpret the content of the claims.

Claims

1. A method for detecting formic acid in povidone K90, comprising the steps of preparing a test solution, preparing a reference solution, and a detection step. It is characterized in that: In the step of preparing the test solution, after diluting the povidone K90 sample, it is passed through a strongly acidic ion exchange resin layer, and the effluent is collected as the test solution; the inner diameter of the filling of the strongly acidic ion exchange resin layer is 0.8 cm, the filling height is 20 mm, and the strongly acidic ion exchange resin layer is always immersed in water; before the povidone K90 sample passes through the strongly acidic ion exchange resin layer, 5 ml of water is first added, and the flow rate is adjusted to 1 ml / min; when the povidone K90 sample passes through the strongly acidic ion exchange resin layer, the first 2 ml of the effluent is discarded, and then 1.5 mL of the effluent is collected as the test solution; in the detection step, high performance liquid chromatography is used for detection; during high performance liquid chromatography detection, a strongly acidic ion exchange resin is used as the filler, perchloric acid - water is used as the mobile phase, the volume ratio of perchloric acid to water is 1:699, and the chromatographic column is an ion exchange column Hi-plex H.

2. The method for detecting formic acid in povidone K90 according to claim 1, It is characterized in that: In the step of preparing the reference solution, the concentration of the formic acid reference solution is 10 μg / ml.

3. The method for detecting formic acid in povidone K90 according to claim 2, It is characterized in that: During high performance liquid chromatography detection, the chromatographic conditions are: the detection wavelength is 210 nm, and the injection volume is 50 μl.

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