Quality detection method of scopolamine butylbromide

Abstract

The invention discloses a quality detection method of scopolamine butylbromide, and relates to the technical field of medicine detection.The method comprises the steps that a sample to be detected is prepared into a test solution, and solubility and the pH value are detected; respectively carrying out specific identification on the sample by adopting a spectrum method and a chemical method; separating and detecting impurities in the sample by adopting a high performance liquid chromatography; determining the content of scopolamine butylbromide in the sample by adopting a potentiometric titration method; carrying out sterility test on the test solution by adopting a membrane filtration method; and comparing the obtained detection data with a preset quality standard, and comprehensively evaluating the quality data. According to the method disclosed by the invention, the content of the scopolamine butylbromide in the raw material medicine is subjected to quality detection according to a plurality of detection standards from physical properties, chemical identification, impurity spectrum, main component content to preparation safety, so that the quality of the scopolamine butylbromide can be more comprehensively evaluated, and the detection accuracy is improved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical testing technology, and in particular to a quality testing method for butyl scopolamine bromide. Background Technology

[0002] Butyroscopine bromide is a clinically crucial anticholinergic drug. It works by effectively inhibiting visceral smooth muscle spasms and is widely used to relieve acute gastrointestinal colic, biliary spasm, and renal colic. As a chemical drug that directly affects key physiological functions, even the slightest deviation in its quality can lead to loss of efficacy or serious adverse reactions. Therefore, establishing a rigorous, precise, and reliable quality control system is an indispensable prerequisite for its clinical application.

[0003] However, existing mainstream pharmacopoeia methods, especially the related substances test, which is a core aspect of quality control, are facing significant technical bottlenecks. Their most prominent drawback lies in the risk of damage to the analytical instruments themselves: current standards generally rely on chromatographic systems using ion-pairing reagents, which are prone to residues in the column and tubing, leading to a rapid decline in column efficiency and an increase in back pressure. This not only significantly increases maintenance costs but also jeopardizes the reproducibility and reliability of test data in the long term. Furthermore, traditional isocratic elution methods may suffer from insufficient resolution and sensitivity when dealing with complex synthetic byproducts and degradation impurities, making it difficult to construct a comprehensive and accurate "impurity profile," thus leaving blind spots for long-term drug stability evaluation and process optimization.

[0004] Therefore, this invention proposes a quality detection method for butyl scopolamine bromide. Summary of the Invention

[0005] This invention provides a quality detection method for butyl scopolamine bromide, which detects the quality of butyl scopolamine bromide from multiple perspectives, thus solving the problem of insufficient accuracy in quality detection in the prior art.

[0006] To solve the above-mentioned technical problems, the present invention provides the following technical solution: This invention provides a method for quality detection of butyl scopolamine bromide, comprising: S1, Prepare the sample to be tested into a test solution and check its solubility and pH value; S2, the specificity of the sample was identified by both spectroscopic and chemical methods; S3 uses high performance liquid chromatography to separate and detect impurities in the sample; S4. The content of butyl scopolamine bromide in the sample was determined by potentiometric titration. S5, Perform sterility testing on the test solution using membrane filtration; S6 compares the obtained test data with the preset quality standards and comprehensively evaluates the quality data.

[0007] The beneficial effects of the technical solution provided by this invention include at least the following: The method of this invention conducts quality testing on the content of butyl scopolamine bromide in the active pharmaceutical ingredient using multiple testing standards, ranging from physical properties, chemical identification, impurity profile, main component content to formulation safety. This forms a more comprehensive, durable, and forward-looking quality control system that is more adapted to modern pharmaceutical production quality management. Furthermore, through comprehensive evaluation, the quality of butyl scopolamine bromide can be more fully assessed, improving the accuracy of the detection. Attached Figure Description

[0008] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0009] Figure 1 This is a flowchart of the quality testing method for butyl scopolamine bromide provided in the embodiments of the present invention. Detailed Implementation

[0010] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings. Example

[0011] A quality testing method for butyl scopolamine bromide.

[0012] Please refer to Figure 1 This is a flowchart of the quality testing method for butyl scopolamine bromide provided in an embodiment of the present invention.

[0013] S1, Prepare the sample to be tested into a test solution and check its solubility and pH value; The sample to be tested is butyl scopolamine bromide raw material, and its pH value should be maintained between 5.5 and 6.5; It should be noted that if 1g (or 1mL) of the active pharmaceutical ingredient can dissolve in less than 1mL of solvent, that is, if the active pharmaceutical ingredient can dissolve quickly and completely in the solvent to form a clear and transparent solution without visible insoluble matter or turbidity, then it meets the solubility requirements; if incomplete dissolution, turbidity, gel-like substances or precipitation occur during the dissolution process, then the solubility is deemed unqualified.

[0014] The pH value of the active pharmaceutical ingredient was checked by weighing a sample, dissolving it in a solution, and then using a pH meter. It should be noted that the pH test procedure for the active pharmaceutical ingredient is as follows: Weigh 0.5g of butylscopolamine bromide active pharmaceutical ingredient, place it in a 50mL volumetric flask, dissolve and dilute it to the mark with freshly boiled and cooled purified water to room temperature, shake, and you will get a sample solution of about 1% (g / v), which can be directly used for pH testing.

[0015] The ratio of butyl scopolamine bromide raw material to purified water in the test solution was 1:300.

[0016] It should be noted that the preparation process of the test solution is as follows: Weigh about 0.10 grams of the raw drug powder and transfer it all to a clean 50 mL volumetric flask, add 30 mL of purified water, and shake or briefly sonicate to completely dissolve the sample to obtain a clear solution; dilute the liquid level in the volumetric flask to the mark with purified water. When the liquid level is close to the mark, use a dropper to slowly add water to ensure that the lowest point of the meniscus of the solution is horizontally tangent to the mark; tighten the stopper, invert the volumetric flask and shake it repeatedly at least 10 times to ensure that the solution concentration is completely uniform.

[0017] S2, the specificity of the sample was identified by both spectroscopic and chemical methods; Spectroscopic methods include ultraviolet spectroscopy identification and infrared spectroscopy identification; The ultraviolet spectroscopy identification process is as follows: the test solution is irradiated with ultraviolet light at wavelengths of 252nm, 257nm and 264nm, and the maximum absorption of the test sample at multiple wavelengths is displayed; It should be noted that the test sample needs to be diluted with 0.01 mol / L hydrochloric acid solution before ultraviolet spectroscopy identification.

[0018] The infrared spectroscopy identification process is as follows: the raw material is mixed with potassium bromide and pressed into a thin sheet. The infrared absorption spectrum of the thin sheet should be compared with the spectrum of butyl scopolamine reference standard. It should be noted that the dried test sample is mixed with potassium bromide, ground evenly, and then pressed into a transparent thin film; the thin film is placed in an infrared spectrometer, and... to The infrared absorption spectrum was obtained by scanning within the wavenumber range; the spectrum of the test sample was compared with the standard spectrum of butyl scopolamine reference standard to obtain the identification result.

[0019] Chemical methods include tropane alkaloid identification reactions and bromide identification reactions; The identification process for tropane alkaloids is as follows: add dilute potassium bismuth iodide test solution to the test sample solution and observe whether an orange-red precipitate is formed; It should be noted that the specific identification process is as follows: Take 10 mg of the raw material and place it in a clean test tube. Add 5 mL of purified water and shake to dissolve it. Then, add 1-2 mL of freshly prepared dilute potassium bismuth iodide test solution dropwise to the solution (potassium bismuth iodide is a general precipitant for alkaloids. Its cationic part can coordinate or ion associate with the tertiary nitrogen atom in the tropane alkaloid molecule to form a complex salt precipitate that is insoluble in water and has obvious color characteristics). Observe the formation of orange-red to brick-red precipitates in the solution.

[0020] The bromide identification process is as follows: add sodium hydroxide solution to the test sample solution and heat it. Observe whether the gas produced can turn moist red litmus paper blue. After acidification, add silver nitrate solution to the remaining solution and observe whether a pale yellow precipitate is formed.

[0021] It should be noted that approximately 50 mg of the raw material is placed in a small test tube or distillation flask with a gas delivery tube, and 2 mL of 10% sodium hydroxide solution is added. The test tube is then slowly heated over an alcohol lamp. A piece of red litmus paper moistened with purified water is suspended at the mouth of the test tube or the outlet of the gas delivery tube. The paper will change from red to blue (under strong alkaline heating conditions, the quaternary ammonium salt structure in the butyl scopolamine molecule undergoes a Hoffmann degradation reaction, releasing free bromide ions and nitrogen-containing alkaline gas, which turns the moistened red litmus paper blue). The remaining solution after heating is cooled and acidified with 10% nitric acid solution. Then, 1-2 mL of 5% silver nitrate solution is added to the acidified solution. The presence of a pale yellow curd-like precipitate is observed, and this precipitate is insoluble in dilute nitric acid (after acidification, the bromide ions in the solution react with silver nitrate to form silver bromide, which becomes a pale yellow precipitate).

[0022] The weight ratio of the active pharmaceutical ingredient to potassium bromide is 1:100; Consistency comparison includes ensuring that the peak position, peak shape, and relative intensity of the characteristic peaks in the spectrum of the test sample are consistent with those of the reference sample. The characteristic peak is located at approximately Absorption peak of stretching vibration of ester carbonyl group (C=O) at wavenumber.

[0023] S3 uses high performance liquid chromatography to separate and detect impurities in the sample; The chromatographic column is a reversed-phase column packed with octadecylsilane-bonded silica gel, the mobile phase is an isocratic elution system containing ion-pairing reagents, and the detection wavelength is a fixed wavelength in the range of 200 nm to 220 nm. It should be noted that the octadecylsilane-bonded silica gel column has a size of 250 mm × 4.6 mm and a packing particle size of 5 μm; the mobile phase uses sodium dodecyl sulfate with a concentration of 0.005-0.02 mol / L as the ion-pairing reagent, and is prepared by mixing phosphoric acid aqueous solution and acetonitrile in equal volume ratios.

[0024] S302, the reference solution and the test solution are injected into the chromatographic system sequentially for analysis, and chromatographic data are collected; The control solution is prepared by quantitatively diluting the test solution; It should be noted that the chromatographic system should be used in the following order: from the control solution to the test solution.

[0025] The analysis process is as follows: identify the main peak (butyl scopolamine bromide) and each impurity peak, and assist in impurity identification by comparing the retention time with the reference standard or by comparing the ultraviolet spectrum with a diode array detector (DAD); and calculate the sum of the peak areas of each impurity peak in the test solution by comparing it with the main peak area of ​​the diluted reference solution (representing the known low concentration of the main component).

[0026] S303 processes chromatographic data, identifies impurity peaks, and performs quantitative calculations.

[0027] It should be noted that the quantitative calculation adopts the self-comparison method, and the calculation formula is: single impurity content (%) = (Au / As) × (Cs / Cu) × 100%, where Au is the peak area of ​​the impurity peak in the test solution; As is the peak area of ​​the main component peak in the self-comparison solution; Cs is the concentration of the self-comparison solution; and Cu is the concentration of the test solution.

[0028] S4, the content of butyl scopolamine bromide in the sample was determined by potentiometric titration. S401 uses a potentiometric titrator equipped with a silver indicator electrode to titrate the test solution and monitors the potential change during the titration process in real time. The potentiometric titrator uses silver nitrate titrant as the titrant, with a concentration of 0.095 mol / L–0.105 mol / L. S402, determine the titration endpoint based on the potential jump point, and record the volume of silver nitrate titrant consumed; S403. Calculate the content of butyl scopolamine bromide based on the volume consumed, the concentration of the silver nitrate titrant, and the sample weight.

[0029] It should be noted that the content of butyl scopolamine bromide is calculated using the following formula: Content (%) = [(V-V0)×C×M / W]×100%, where V is the volume of silver nitrate titrant consumed by the test sample. The blank test volume is represented by C, where C is the actual concentration of the silver nitrate titrant, M is the molar mass of butyl scopolamine, and W is the sample weight.

[0030] The process for determining the titration endpoint is as follows: During the titration process, titration volume data and corresponding potential measurement data are collected and stored in real time; based on the volume data and potential data, the rate of change of potential with respect to titration volume, i.e., the first derivative, is calculated in real time; the titration volume corresponding to the global maximum value of the first derivative is determined as the titration endpoint.

[0031] It should be noted that the calculation of the rate of change (ΔE / ΔV) is based on the preset continuous titration volume increment range; the determination of the titration endpoint also needs to meet the following condition: the maximum value of the first derivative (ΔE / ΔV) must exceed the preset threshold sensitivity.

[0032] Potential measurement data were collected after each addition of a constant, small volume increment of titrant.

[0033] S5, Perform sterility testing on the test solution using membrane filtration; The testing process of the membrane filtration method is as follows: a specified amount of the test solution is filtered through a sterile filter membrane, and the filter membrane is rinsed with an appropriate amount of sterile buffer solution. Then the filter membrane is transferred to thioglycolate fluid medium and tryptic soy peptone liquid medium for observation. The pore size of the sterile filter membrane is 0.22 μm.

[0034] It should be noted that the culture medium needs to be incubated at 30-35℃ and 20-25℃ for no less than 14 days to observe whether there is microbial growth.

[0035] S6. The obtained test data is compared with the preset quality standards to comprehensively evaluate the quality data; S601 compares each measured result with the corresponding limit value or requirement in the preset quality standard to make a single conformity judgment; S602, based on the results of all individual conformity assessments, comprehensively judge the conformity status of the sample; The judgment criteria are to compare the measured data with the statutory standards, and classify the qualified samples according to the number of items that meet the internal control standards or the degree of compliance of key items.

[0036] It should be noted that if any one or more individual test items fail to meet the requirements, the final overall judgment will be that the test is unqualified.

[0037] The judgment criteria also include trend analysis of key quality attributes. The specific criteria are: to compare the measured data of this test, especially the data of key quality attributes, with the historical data of the same batch of the product, and to assess whether the fluctuation is within the normal and controlled historical trend range.

[0038] Furthermore, it should be noted that the present invention can be provided as a method, apparatus, or computer program product. Therefore, embodiments of the present invention can take the form of a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects. Moreover, embodiments of the present invention can take the form of a computer program product implemented on one or more computer-usable storage media containing computer-usable program code.

[0039] The embodiments of the present invention are described with reference to flowchart illustrations and / or block diagrams of methods, terminal devices (systems), and computer program products according to embodiments of the present invention. It should be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, embedded processor, or other programmable data processing terminal device to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing terminal device, generate instructions for implementing the flowchart illustrations. Figure 1 One or more processes and / or boxes Figure 1 A device that provides the functions specified in one or more boxes.

[0040] These computer program instructions may also be stored in a computer-readable storage medium that can direct a computer or other programmable data processing terminal device to operate in a particular manner, such that the instructions stored in the computer-readable storage medium produce an article of manufacture including instruction means, which are implemented in a process Figure 1 One or more processes and / or boxes Figure 1 The functions specified in one or more boxes. These computer program instructions may also be loaded onto a computer or other programmable data processing terminal equipment to cause a series of operational steps to be performed on the computer or other programmable terminal equipment to produce a computer-implemented process, thereby providing instructions that execute on the computer or other programmable terminal equipment for implementing the process. Figure 1 One or more processes and / or boxes Figure 1 The steps of the function specified in one or more boxes.

[0041] It should also be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. The terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or terminal device that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or terminal device. Without further limitation, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or terminal device that includes said element.

[0042] Finally, it should be noted that the above description represents a preferred embodiment of the present invention. It should be pointed out that although preferred embodiments have been described, those skilled in the art, once they understand the basic inventive concept of the present invention, can make various improvements and modifications without departing from the principles described herein. These improvements and modifications should also be considered within the scope of protection of the present invention. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the embodiments of the present invention.

Claims

1. A method for quality detection of butyl scopolamine bromide, characterized in that, include: S1, Prepare the sample to be tested into a test solution and check its solubility and pH value; S2, the specificity of the sample was identified by both spectroscopic and chemical methods; S3 uses high performance liquid chromatography to separate and detect impurities in the sample; S4. The content of butyl scopolamine bromide in the sample was determined by potentiometric titration. S5, Perform sterility testing on the test solution using membrane filtration; S6 compares the obtained test data with the preset quality standards and comprehensively evaluates the quality data.

2. The quality detection method for butyl scopolamine bromide as described in claim 1, characterized in that, S1 prepares the sample to be tested into a test solution and checks its solubility and pH value, wherein: The sample to be tested is butyl scopolamine bromide raw material, and its pH value should be maintained between 5.5 and 6.5; The pH value of the active pharmaceutical ingredient was checked by weighing a sample, dissolving it in a solution, and then using a pH meter. The ratio of butyl scopolamine raw material to purified water in the test solution was 1:

300.

3. The quality detection method for butyl scopolamine bromide as described in claim 1, characterized in that, S2 uses both spectroscopic and chemical methods to specifically identify the samples, wherein: The spectroscopic methods include ultraviolet spectroscopy identification and infrared spectroscopy identification; The ultraviolet spectroscopy identification process is as follows: the test solution is irradiated with ultraviolet light at wavelengths of 252nm, 257nm and 264nm to show the maximum absorption of the test sample at multiple wavelengths; The infrared spectroscopy identification process is as follows: the raw material is mixed with potassium bromide and pressed into a thin sheet, and the infrared absorption spectrum of the thin sheet is compared with the spectrum of butyl scopolamine reference standard. The chemical methods include tropane alkaloid identification reactions and bromide identification reactions; The identification process for tropane alkaloids is as follows: add dilute potassium bismuth iodide test solution to the test sample solution and observe whether an orange-red precipitate is formed. The bromide identification process is as follows: sodium hydroxide solution is added to the test sample solution and heated. The gas produced is observed to turn moist red litmus paper blue. After acidification, silver nitrate solution is added to the remaining solution to observe whether a pale yellow precipitate is formed.

4. The quality detection method for butyl scopolamine bromide as described in claim 3, characterized in that, The infrared spectroscopy identification process is as follows: the active pharmaceutical ingredient is mixed with potassium bromide and pressed into thin sheets. The infrared absorption spectrum of the thin sheets should be compared with the spectrum of butyl scopolamine bromide reference standard, wherein: The weight ratio of the active pharmaceutical ingredient to potassium bromide is 1:

100. The consistency comparison includes ensuring that the peak position, peak shape, and relative intensity of the characteristic peaks in the spectrum of the test sample are consistent with those of the spectrum of the reference sample. The characteristic peak is located at approximately Absorption peak of stretching vibration of ester carbonyl group (C=O) at wavenumber.

5. The quality detection method for butyl scopolamine bromide as described in claim 1, characterized in that, S3 uses high-performance liquid chromatography (HPLC) to separate and detect impurities in the sample, wherein: S301, Establish a chromatographic system including a chromatographic column, mobile phase, and detection wavelength; The chromatographic column is a reversed-phase chromatographic column packed with octadecylsilane-bonded silica gel, the mobile phase is an isocratic elution system containing ion-pairing reagents, and the detection wavelength is a fixed wavelength in the range of 200 nm to 220 nm. S302, the reference solution and the test solution are injected into the chromatographic system sequentially for analysis, and chromatographic data are collected; The control solution was prepared by quantitatively diluting the test solution. S303 processes chromatographic data, identifies impurity peaks, and performs quantitative calculations.

6. The quality detection method for butyl scopolamine bromide as described in claim 1, characterized in that, The S4 method uses potentiometric titration to determine the content of butyl scopolamine bromide in the sample, wherein: S401 uses a potentiometric titrator equipped with a silver indicator electrode to titrate the test solution and monitors the potential change during the titration process in real time. The potentiometric titrator uses silver nitrate titrant as the titrant, and the concentration of the silver nitrate titrant is 0.095 mol / L-0.105 mol / L; S402, determine the titration endpoint based on the potential jump point, and record the volume of silver nitrate titrant consumed; S403, calculate the content of butyl scopolamine bromide based on the consumed volume, the concentration of silver nitrate titrant, and the sample weight.

7. The quality detection method for butyl scopolamine bromide as described in claim 6, characterized in that, The titration endpoint is determined based on the potential jump point, and the volume of silver nitrate titrant consumed is recorded, wherein: The process for determining the titration endpoint is as follows: during the titration process, titration volume data and corresponding potential measurement data are collected and stored in real time; based on the volume data and potential data, the rate of change of potential with respect to titration volume, i.e., the first derivative, is calculated in real time; the titration volume corresponding to the global maximum value of the first derivative is determined as the titration endpoint.

8. The quality detection method for butyl scopolamine bromide as described in claim 1, characterized in that, S5 uses a membrane filtration method to perform sterility testing on the test solution, wherein: The inspection process of the membrane filtration method is as follows: a specified amount of test solution is filtered through a sterile filter membrane, and the filter membrane is rinsed with an appropriate amount of sterile buffer solution. Then the filter membrane is transferred to thioglycolate fluid medium and tryptic soy peptone liquid medium for observation. The sterile filter membrane has a pore size of 0.22 μm.

9. The quality detection method for butyl scopolamine bromide as described in claim 1, characterized in that, S6 compares the obtained detection data with preset quality standards and comprehensively evaluates the quality data, wherein: S601 compares each measured result with the corresponding limit value or requirement in the preset quality standard to make a single conformity judgment; S602, based on the results of all individual conformity assessments, comprehensively judge the conformity status of the sample; The judgment criteria are to compare the measured data with the statutory standards, and to classify the qualified samples according to the number of items that meet the internal control standards or the degree of compliance of key items.

10. The quality detection method for butyl scopolamine bromide as described in claim 9, characterized in that, The sample's qualification status is comprehensively judged based on all individual compliance determination results, wherein: The judgment criteria also include key quality attribute trend analysis. The specific criteria are: compare the measured data of this test, especially the key quality attribute data, with the historical data of the same batch of the product to assess whether the fluctuation is within the normal and controlled historical trend range.

Images