Method for determining content of hydroxypropyl starch in pharmaceutical preparation
The HPLC-CAD method determines the content of hydroxypropyl starch in the drug preparation, which solves the problem that cannot be accurately measured in the prior art, and achieves efficient and accurate detection results.
Patent Information
- Application Number
- CN202510023328.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-07
- Publication Date
- 2025-04-25
AI Technical Summary
The prior art cannot simply and accurately determine the content of hydroxypropyl starch in pharmaceutical preparations. The current Chinese Pharmacopoeia uses gas chromatography to operate in complex operations, and the sample needs a large amount, which is not suitable for accurate measurement.
The HPLC-CAD method was used to determine the content of hydroxypropyl starch in the drug preparation, and the standard curve was established by the preparation of the reference solution and the test sample solution, and the content of hydroxypropyl starch was calculated using the external standard standard curve method.
The accurate determination of the content of hydroxypropyl starch in the drug preparation is achieved. The operation steps are simple, the detection time is short, the detection efficiency is high, there is no signal interference in the test sample, the linear relationship is good, the precision is high, and the recovery rate is between 98% and 105%.
Smart Images
Figure CN119881131A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of drug detection, in particular to a method for determining the content of hydroxypropyl starch in a drug preparation. Background Art
[0002] Hydroxypropyl starch (HPS) is a type of modified starch and a hydroxypropyl ether of cellulose. It is a white powder that is easily soluble in cold water and soluble in methanol, ethanol, isopropanol and propylene glycol. As the requirements for generic drug research become more and more stringent, the demand for the content determination of excipients in the reverse engineering of reference preparations is increasing. As one of the key excipients, hydroxypropyl starch can be used as a binder for wet granulation, as a binder for direct powder tableting, and as a thickener. Therefore, establishing an accurate determination method for the content of hydroxypropyl starch in reference preparations is crucial for the development of related drug preparations.
[0003] At present, no relevant literature on the determination of hydroxypropyl starch content in pharmaceutical preparations has been found. The current method for determining the hydroxypropyl starch content in the Chinese Pharmacopoeia is a general method, which uses gas chromatography to determine the hydroxypropoxy content. The operation process of this method is complicated and requires a large amount of sample, which is not suitable for the accurate determination of the hydroxypropyl starch content in pharmaceutical preparations. Summary of the invention
[0004] In view of the above-mentioned shortcomings of the prior art, the object of the present invention is to provide a method for determining the content of hydroxypropyl starch in a pharmaceutical preparation, so as to solve the problem that the prior art cannot simply and accurately determine the content of hydroxypropyl starch in a pharmaceutical preparation.
[0005] To achieve the above object and other related objects, the present invention provides a method for determining the content of hydroxypropyl starch in a pharmaceutical preparation, comprising the following steps: (1) Preparation of reference solution: Weigh an appropriate amount of hydroxypropyl starch reference solution, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 h, and then dilute it with a diluent to prepare a series of hydroxypropyl starch reference solutions of different concentrations; (2) Preparation of test solution: Weigh an appropriate amount of drug preparation, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 h, and then dilute it with a diluent to prepare the test solution; (3) Establishing a standard curve: using HPLC-CAD (liquid chromatography-electrospray ionization detector) method to detect the series of hydroxypropyl starch reference solutions prepared in step (1), respectively, to obtain the peak area of the target peak in the reference solution, to fit the peak area with the corresponding solution concentration to the standard curve, and to calculate the standard curve; (4) Determination of hydroxypropyl starch content: The test solution prepared in step (2) is detected by HPLC-CAD method to obtain the peak area of the test solution, and the content of hydroxypropyl starch in the test solution is calculated by external standard curve method.
[0006] Preferably, in step (1) and step (2), the diluent is an acetonitrile-water solution, and the volume ratio of acetonitrile to water in the acetonitrile-water solution is 50:50.
[0007] Preferably, in step (1), the concentration range of the series of hydroxypropyl starch reference solutions is 0.05-5 mg / ml.
[0008] Preferably, in step (3) and step (4), the chromatographic conditions of HPLC-CAD are: Chromatographic column: Shodex Asahipak NH2P-50 4E, specification 250*4.6mm, 5μm; Column temperature: 25~45℃; Injection volume: 10~30μl; Mobile phase: aqueous solution as mobile phase A, acetonitrile as mobile phase B; Flow rate: 0.5~1.5ml / min; Isocratic elution, elution ratio 50:50; Detector: Electrospray detector, model: Power Function 1.0, Data Rate 5Hz, Filter3.6.
[0009] As described above, a method for determining the content of hydroxypropyl starch in a pharmaceutical preparation of the present invention has the following beneficial effects: 1. The present invention adopts HPLC-CAD method to detect the content of hydroxypropyl starch in pharmaceutical preparations, with simple operation steps, short detection time and higher detection efficiency; no signal interference in the test sample, good specificity; good linear relationship and high precision; recovery rate is between 98% and 105%, high accuracy and good repeatability. This detection method can accurately determine the content of hydroxypropyl starch in pharmaceutical preparations, and becomes an important means for analyzing hydroxypropyl starch in reference preparations.
[0010] 2. The present invention performs strong acid treatment on the reference substance and the test substance so that the effective ingredients can be completely dissolved in the diluent, thereby improving the accuracy of the detection. BRIEF DESCRIPTION OF THE DRAWINGS
[0011] In order to more clearly illustrate the technical solution of the embodiment of the present invention, the following briefly introduces the drawings required for describing the embodiment. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
[0012] Figure 1 The chromatograms are of hydroxypropyl starch, reference preparation, D-glucose positioning solution and blank solution detected in Example 1 of the present invention; Figure 2 The standard curve diagram of the hydroxypropyl starch reference solution established in the present invention. DETAILED DESCRIPTION
[0013] The following is a description of the implementation of the present invention by means of specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification.
[0014] Example 1: Specificity test Solution preparation: Weigh an appropriate amount of hydroxypropyl starch reference substance, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 hours, and then dilute it with an acetonitrile-water solution (50:50) to obtain a hydroxypropyl starch solution. Weigh an appropriate amount of the reference preparation containing hydroxypropyl starch, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 hours, and then dilute it with an acetonitrile-water solution (50:50) to prepare a reference preparation solution. The blank solution is an acetonitrile-water solution (50:50).
[0015] The parameters of the HPLC-CAD method were set as follows: Shodex Asahipak NH2P-50 4E (250*4.6mm, 5μm) was used as the chromatographic column, the column temperature was 35°C, the injection volume was 20μl; aqueous solution was used as mobile phase A, acetonitrile was used as mobile phase B, the flow rate was 1.0ml / min; isocratic elution, the elution ratio was 50:50; the detector was an electrospray detector, model Power Function 1.0, DataRate 5Hz, Filter 3.6.
[0016] The HPLC-CAD method was used to measure the hydroxypropyl starch solution, the reference preparation solution, the D-glucose positioning solution and the blank solution, and the chromatograms were recorded. Figure 1 shown.
[0017] The results showed that the blank solution and D-glucose positioning solution had no interference at the hydroxypropyl starch peak, indicating that the HPLC-CAD method had good specificity.
[0018] Example 2: Linearity test (1) Preparation of reference solution: Weigh an appropriate amount of hydroxypropyl starch reference substance, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 h, and then dilute it with acetonitrile-water solution (50:50) to obtain a series of hydroxypropyl starch reference substance solutions with concentrations of 0.1335 mg / ml, 0.1994 mg / ml, 0.2560 mg / ml, 0.2942 mg / ml, and 0.4017 mg / ml, respectively; (2) Setting the parameters of the HPLC-CAD method: Shodex Asahipak NH2P-50 4E (250*4.6mm, 5μm) was used as the chromatographic column, the column temperature was 35°C, the injection volume was 20μl; aqueous solution was used as mobile phase A, acetonitrile was used as mobile phase B, the flow rate was 1.0ml / min; isocratic elution, the elution ratio was 50:50; the detector was an electrospray detector, model Power Function 1.0, Data Rate 5Hz, Filter 3.6; (3) Establishing a standard curve: The series of hydroxypropyl starch reference solutions prepared in step (1) were respectively detected by the HPLC-CAD method to obtain the peak area of the target peak in the reference solution. The specific data are shown in Table 1. The peak area and the corresponding solution concentration were fitted to the standard curve to calculate the standard curve.
[0019] Table 1. Linearity test results
[0020] The results showed that the standard curve of hydroxypropyl starch was y=21.288x+0.1358, R 2 =0.9982, satisfying R 2 ≥0.990, the linear relationship is good, and the standard curve after fitting is as follows Figure 2 shown.
[0021] Example 3: Accuracy Test A method for determining the content of hydroxypropyl starch in a pharmaceutical preparation comprises the following steps: (1) Preparation of reference solution: Weigh an appropriate amount of hydroxypropyl starch reference substance, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 h, and then dilute it with acetonitrile-water solution (50:50) to obtain a series of hydroxypropyl starch reference substance solutions with concentrations of 0.1335 mg / ml, 0.1994 mg / ml, 0.2560 mg / ml, 0.2942 mg / ml, and 0.4017 mg / ml, respectively; (2) Preparation of test solution: Weigh an appropriate amount of drug preparation, place in a 1M hydrochloric acid solution in a 105°C water bath for 2 h, and then dilute with acetonitrile-water solution (50:50) to prepare the test solution; (3) Setting the parameters of the HPLC-CAD method: Shodex Asahipak NH2P-50 4E (250*4.6mm, 5μm) was used as the chromatographic column, the column temperature was 35°C, the injection volume was 20μl; aqueous solution was used as mobile phase A, acetonitrile was used as mobile phase B, the flow rate was 1.0ml / min; isocratic elution, the elution ratio was 50:50; the detector was an electrospray detector, model Power Function 1.0, Data Rate 5Hz, Filter 3.6; (4) Establishing a standard curve: The series of hydroxypropyl starch reference solutions prepared in step (1) were respectively detected by HPLC-CAD method to obtain the peak area of the target peak in the reference solution. The specific data are shown in Table 1. The peak area and the corresponding solution concentration were fitted to the standard curve to obtain the standard curve y=21.288x+0.1358, R 2 =0.9982; (5) Determination of hydroxypropyl starch content: The test solution prepared in step (2) was detected by HPLC-CAD method. After the peak area of the test solution was obtained, the content of hydroxypropyl starch in the test solution was calculated by external standard curve method. The test results are shown in Table 2.
[0022] Table 2. Accuracy test results
[0023] The results showed that the recovery rate of hydroxypropyl starch was in the range of 98%~105%, and the RSD was 2%. It can be seen that this method has high accuracy and can accurately detect the content of hydroxypropyl starch in the test sample.
[0024] In summary, the present invention uses HPLC-CAD method to detect the content of hydroxypropyl starch in pharmaceutical preparations, with simple operation steps, short detection time, higher detection efficiency, no signal interference in the test sample, good specificity, good linear relationship, high precision, recovery rate between 98% and 105%, high accuracy, and good repeatability. Therefore, the present invention effectively overcomes various shortcomings in the prior art and has high industrial utilization value.
[0025] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.
Claims
1. A method for determining the content of hydroxypropyl starch in a pharmaceutical preparation, characterized in that: The following steps are involved: (1) Preparation of reference solution: Weigh an appropriate amount of hydroxypropyl starch reference solution, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 h, and then dilute it with a diluent to prepare a series of hydroxypropyl starch reference solutions of different concentrations; (2) Preparation of test solution: Weigh an appropriate amount of drug preparation, place it in a 1M hydrochloric acid solution in a 105°C water bath for 2 h, and then dilute it with a diluent to prepare the test solution; (3) Establishing a standard curve: using the HPLC-CAD method to respectively detect the series of hydroxypropyl starch reference solutions prepared in step (1), obtain the peak area of the target peak in the reference solution, perform standard curve fitting on the peak area and the corresponding solution concentration, and calculate the standard curve; (4) Determination of hydroxypropyl starch content: The test solution prepared in step (2) is detected by HPLC-CAD method to obtain the peak area of the test solution, and the content of hydroxypropyl starch in the test solution is calculated by external standard curve method.
2. A method for determining the content of hydroxypropyl starch in a pharmaceutical preparation according to claim 1, characterized in that: In step (1) and step (2), the diluent is an acetonitrile-water solution.
3. A method for determining the content of hydroxypropyl starch in a pharmaceutical preparation according to claim 2, characterized in that: The volume ratio of acetonitrile to water in the acetonitrile-water solution is 50:
50.
4. A method for determining the content of hydroxypropyl starch in a pharmaceutical preparation according to claim 1, characterized in that: In step (1), the concentration range of the series of hydroxypropyl starch reference solutions is 0.05~5 mg / ml.
5. A method for determining the content of hydroxypropyl starch in a pharmaceutical preparation according to claim 1, characterized in that: In step (3) and step (4), the chromatographic conditions of the HPLC-CAD method are: Chromatographic column: Shodex Asahipak NH2P-50 4E, specification 250*4.6mm, 5μm; Column temperature: 25~45℃; Injection volume: 10~30μl; Mobile phase: aqueous solution as mobile phase A, acetonitrile as mobile phase B; Flow rate: 0.5~1.5ml / min; Isocratic elution, elution ratio 50:50; Detector: Electrospray detector, model: Power Function 1.0, Data Rate 5Hz, Filter 3.6.