Application of differential scanning calorimetry in ambrotone quality control
The heat flux and enthalpy of ambroxol samples were determined by differential scanning calorimetry, which solved the problem of ambroxol quality control in the existing technology and achieved rapid and accurate determination of ambroxol content.
Patent Information
- Application Number
- CN202511401687.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-28
- Publication Date
- 2026-02-06
AI Technical Summary
Existing technologies lack simple and efficient methods for controlling the quality of ambergris.
Differential scanning calorimetry was used to determine the ambroxol content in the samples. The peak area and enthalpy of the heat flux were recorded to calculate the ambroxol content.
A rapid, efficient, simple and reproducible method is provided for the quality control of ambroxol, which can accurately determine the ambroxol content.
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Figure CN121476290A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of essence and food additive, in particular to application of differential scanning calorimetry in quality control of ambergris ketone. BACKGROUND
[0002] Ambergris is a very precious animal spice, which is a pathological calculus formed by the undigested food (especially squid) in the stomach and intestines of sperm whale. Due to the limited natural source of ambergris, people have developed synthetic spices with the fragrance of ambergris to replace natural products, and different varieties have been developed. Ambergris ketone is one of them. Ambergris ketone has a soft and woody ambergris fragrance, and the fragrance is transparent and long-lasting. It can be used as a spice or a fixed fragrance agent, and is widely used in the essence and spice industry. Ambergris ketone as a high value-added synthetic spice is particularly important in quality control. However, there is a lack of a method for simply and efficiently controlling the quality of ambergris ketone in the prior art.
[0003] Therefore, there is a need in the art to develop a method for simply and efficiently determining ambergris ketone. SUMMARY
[0004] The purpose of the present application is to provide a method for simply and efficiently determining ambergris ketone.
[0005] The present application provides a method for determining ambergris ketone, which comprises:
[0006] The ambergris ketone sample is determined by differential scanning calorimetry.
[0007] Preferably, the method is a quantitative and / or qualitative method.
[0008] Preferably, the method comprises a method for determining the content of ambergris ketone.
[0009] Preferably, the method is an in vitro method.
[0010] Preferably, the method is a non-diagnostic and non-therapeutic method.
[0011] Preferably, the differential scanning calorimetry is performed on a differential scanning calorimeter.
[0012] Preferably, the operating parameters of the differential scanning calorimeter include a temperature rise range of 100-320℃ and a temperature rise rate of 10℃ / min.
[0013] Preferably, the operating parameters of the differential scanning calorimeter include the following:
[0014] Close the oxygen valve, open the nitrogen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the drying gas flow rate to 140-160 ml / min, set the nitrogen flow rate to 45-55 ml / min, weigh the ambergris sample and place it in the sample position of the instrument, while the reference position of the instrument is the blank control; the heating range is 100-320℃, and the heating rate is 10℃ / min.
[0015] Preferably, the operating parameters of the differential scanning calorimeter include the following:
[0016] Close the oxygen valve, open the nitrogen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the drying gas flow rate to 140-160 ml / min, set the nitrogen flow rate to 45-55 ml / min, weigh the ambergris sample and place it in the aluminum crucible, cover it, press it with a tablet press, poke a small hole in the lid, and place it in the sample position of the instrument. At the same time, make an empty standard aluminum crucible, poke a small hole in the aluminum lid, and place it in the reference position of the instrument. The heating range is 100-320℃, and the heating rate is 10℃ / min.
[0017] Preferably, the operating parameters of the differential scanning calorimeter include the following:
[0018] Close the oxygen valve, open the nitrogen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the drying gas flow rate to 150 ml / min, set the nitrogen flow rate to 50 ml / min, weigh the ambergris sample and place it in the aluminum crucible, cover it, press it with a tablet press, poke a small hole in the lid, and place it in the sample position of the instrument. At the same time, make an empty standard aluminum crucible, poke a small hole in the aluminum lid, and place it in the reference position of the instrument. The heating range is 100-320℃, and the heating rate is 10℃ / min.
[0019] Preferably, the mass of the ambroxol sample is 5-20 mg, for example, 5-10 mg.
[0020] Preferably, the mass of the ambergris sample is accurate to 0.01 mg.
[0021] Preferably, the volume of the aluminum crucible is 30-50 μl, more preferably 35-45 μl, and even more preferably 40 μl.
[0022] Preferably, the operating parameters of the differential scanning calorimeter include the following:
[0023] Close the oxygen valve, open the nitrogen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the drying gas flow rate to 150 ml / min, set the nitrogen flow rate to 50 ml / min, weigh 5-20 mg (preferably 5-10 mg) ambroxol sample and place it in a 40 μl aluminum crucible, cover it, press it with a tablet press, poke a small hole in the lid, and place it in the sample position of the instrument. At the same time, make an empty 40 μl standard aluminum crucible, poke a small hole in the aluminum lid, and place it in the reference position of the instrument. The heating range is 100-320℃, and the heating rate is 10℃ / min.
[0024] Preferably, before determining ambroxol using a differential scanning calorimeter, the instrument is calibrated, and the calibration includes:
[0025] Open the oxygen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the gas flow rate to 50 ml / min, clean the furnace body and sensor of the differential scanning calorimeter, and then calibrate the standard samples indium (In) and zinc (Zn) of the differential scanning calorimeter. The final test results of the standard substances In and Zn are within the error limit, and the differential scanning calorimeter calibration is passed.
[0026] Preferably, the ambroxol content in the ambroxol sample is determined by the external standard method.
[0027] Preferably, the ambroxol content in the ambroxol sample is determined by the external standard method using ambroxol reference standard.
[0028] Preferably, the determination parameters of the differential scanning calorimetry include heat flux peak area and / or enthalpy.
[0029] Preferably, the ambergris content in the ambergris sample is determined and calculated by recording the peak area and / or enthalpy of the heat flux value using differential scanning calorimetry as the measurement index.
[0030] Preferably, the ambergris content in the ambergris sample is determined by recording the peak area of the heat flux value and the calculated enthalpy of differential scanning calorimetry as the measurement index.
[0031] Preferably, the ambroxol content in the ambroxol sample is determined by comparing the peak area of the heat flux value of the ambroxol sample with that of the ambroxol reference standard.
[0032] Preferably, the ambroxol content in the ambroxol sample is determined by comparing the enthalpy of the ambroxol sample with that of the ambroxol reference standard.
[0033] Preferably, the ambroxan sample includes ambroxan raw material or ambroxan reference standard.
[0034] Preferably, the ambergris raw material includes food raw materials, food additive raw materials, or pharmaceutical raw materials.
[0035] Preferably, the ambroxan sample comprises ambroxan raw material.
[0036] Preferably, the purity of ambergris in the ambergris sample is greater than 90%.
[0037] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description
[0038] Figure 1 The DSC curves are shown for different heating rates.
[0039] Figure 2 These are DSC curves at the same heating rate.
[0040] Figure 3 The DSC curves of ambergris samples at the same heating rate are shown. Detailed Implementation
[0041] This invention provides a method for determining ambroxol, comprising determining the ambroxol sample using differential scanning calorimetry (DSC). This invention measures the enthalpy of a known substance and the analyte during the absorption or release of heat under temperature changes using DSC. The content of the analyte is calculated by comparing the enthalpy of the known substance with that of the analyte. Compared to traditional gas chromatography, the DSC method for determining ambroxol content offers advantages such as simple operation, low cost, small sample volume, and no need for sample dilution, making it significant for the quality control and application of ambroxol products.
[0042] the term
[0043] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.
[0044] As used herein, the terms “comprising,” “including,” and “containing” are used interchangeably and include not only open-ended definitions but also semi-closed and closed definitions. In other words, the terms include “consisting of” and “substantially consisting of”.
[0045] As used in this article, the term “differential scanning calorimetry” is abbreviated as DSC.
[0046] As used in this article, the CAS number for the term "ambromine" is 54464-57-2.
[0047] method
[0048] Differential scanning calorimetry is mainly used to measure the temperature and heat flow related to thermal transformation inside the sample, as well as the temperature difference between the sample and the reference material and the temperature. Its principle is that when a substance is heated or cooled, it often undergoes physical or chemical changes such as melting, solidification, crystal transformation, decomposition, and combination when it reaches a certain temperature, which is accompanied by a change in enthalpy, thus producing a thermal effect.
[0049] This invention provides a method for determining ambroxol, the method comprising:
[0050] The ambergris sample was determined by differential scanning calorimetry.
[0051] The method described in this invention can be used to determine the content of ambroxol. For example, the content of ambroxol in an ambroxol sample can be determined by the external standard method.
[0052] Specifically, the method for determining ambroxol according to the present invention is as described in the first aspect of the present invention above.
[0053] The main technical effects of this invention include:
[0054] This invention develops a method for determining ambroxol using differential scanning calorimetry (DSC). DSC can be used to determine the content of ambroxol, thereby enabling its quality control. DSC has advantages such as speed, efficiency, simple operation, and good reproducibility. The establishment of this method provides a fast and efficient analytical method for the quality control of ambroxol, which is of great significance for the application of ambroxol.
[0055] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer.
[0056] Example 1
[0057] 1. Instruments, reagents and samples
[0058] 1.1 Instruments
[0059] Differential scanning calorimeter (DSC3), instrument model: METTLER TOLEDO Thermal Analysis System DSC3 (Mettler-Toledo Instruments Ltd.).
[0060] 1.2 Reagents and Samples
[0061] Ambroxol reference standard (purity 90%, batch number C15363457, CAS: 54464-57-2, Shanghai Maclean Biochemical Technology Co., Ltd.); 3 batches of ambroxol samples (manufacturer: Fujian Nanping Longsheng Fragrance and Flavor Co., Ltd., batch numbers: 2383311, 2310181, 2312221 respectively).
[0062] 2. Experimental Procedure
[0063] 2.1 Instrument Calibration
[0064] Open the oxygen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the gas flow rate to 50 ml / min, clean the furnace body and sensor of the differential scanning calorimeter, and then calibrate the standard samples indium (In) and zinc (Zn) of the differential scanning calorimeter. The final test results of the standard substances In and Zn are within the error limit, and the differential scanning calorimeter calibration is passed.
[0065] 2.2 Experimental Methods and Results
[0066] 2.2.1 Investigating the effect of different heating rates on the determination of the enthalpy of ambroxol reference standard: The oxygen valve was closed, the nitrogen valve was opened, the auxiliary pressure gauge was adjusted to less than 0.1 MPa, the drying gas flow rate was adjusted to 150 ml / min, and the nitrogen flow rate was set to 50 ml / min. Six portions of ambroxol reference standard, 5-20 mg (accurate to 0.01 mg), were accurately weighed and placed in separate 40 μl standard aluminum crucibles. The crucibles were covered, pressed into tablets, and a small hole was punched in the lid before placing them in the sample position of the instrument. Simultaneously, an empty 40 μl standard aluminum crucible was prepared, and a small hole was punched in the aluminum lid before placing it in the reference position of the instrument. Heating ranges were: 40-320℃, heating rate 5℃ / min; 40-350℃, heating rate 10℃ / min; 40-380℃, heating rate 15℃ / min. Two parallel studies were performed at each heating rate, and the peak area of the DSC heat flux was recorded. The results are shown in Table 1. Figure 1 .
[0067] 2.2.2 Investigating the effect of the same heating rate on the determination of the enthalpy of ambroxol reference standard: Accurately weigh 5-10 mg (accurate to 0.01 mg) of ambroxol reference standard in five portions. The heating range was 100-320℃, and the heating rate was 10℃ / min. The peak area of the DSC heat flux value was recorded. The results are shown in Table 2 and... Figure 2 .
[0068] 2.2.3 Sample Testing: Accurately weigh 5-10 mg (accurate to 0.01 mg) of three batches of ambroxol samples (2383311, 2310181, and 2312221), with two replicates for each batch. The heating range was 100-320℃ at a rate of 10℃ / min. The peak area of the DSC heat flux was recorded. The results are shown in Table 3. Figure 3 .
[0069] Table 1. DSC test results of ambergris reference standard at different heating rates
[0070]
[0071] Table 2. DSC test results of ambergris reference standard at the same heating rate.
[0072]
[0073] Table 3. DSC results of ambergris samples
[0074]
[0075]
[0076] Table 4 Comparison of DSC and gas chromatography results for ambergris samples
[0077]
[0078] 2.3 Discussion
[0079] 2.3.1 Results of DSC curve determination at different heating rates
[0080] DSC analysis was performed on ambroxol reference standard at the same initial temperature of 40℃, different heating rates of 5℃ / min, 10℃ / min, and 15℃ / min, and different termination temperatures. (See Table 1 and...) Figure 1 It can be observed that when the heating rate changes from 5℃ / min to 10℃ / min, the enthalpy and peak value of the control ambergris decrease, without thermal hysteresis. When the rate changes from 10℃ / min to 15℃ / min, the enthalpy and peak value of the control ambergris increase, with obvious thermal hysteresis, which increases the width and height of the endothermic peak of the sample.
[0081] 2.3.2 Enthalpy determination results of ambergris (reference ambergris) within a heating range of 100-320℃ at a heating rate of 10℃ / min: (The results are presented in the original text.) Figure 2 It can be seen that the DSC curves of the five reference ambroxols all have a characteristic downward endothermic "fingerprint" peak. The average enthalpy of the five references is -225.56 J / g with an RSD of 1.0%, and the average peak temperature is 278.73℃ with an RSD of 1.8%, indicating good reproducibility.
[0082] 2.3.3 Enthalpy determination results of ambergris samples with a heating range of 100-320℃ and a heating rate of 10℃ / min: From Figure 3 As can be seen, the peak shapes of samples 2383311 and 2310181 are similar to those of the control ambroxol. Sample 2312221, however, shows a significant difference from the control ambroxol, exhibiting a large upward exothermic peak around 160℃ and a broad, gently descending endothermic peak around 280℃. The ambroxol content of the samples can be calculated by comparing its enthalpy with that of a 90% concentration control ambroxol. The content determination results for the three batches of samples are shown in Table 3. The ambroxol contents of batches 2383311 and 2310181 are 91.1% and 92.4%, respectively, both greater than 90%. The ambroxol content of batch 2312221 is 40.2%, less than 90%.
[0083] 2.3.4 Comparative Experiment - Gas Chromatography (GC) Method: Accurately measure 1 ml of each of the three batches of ambroxol samples and add them to a 50 ml volumetric flask. Add anhydrous ethanol and dilute to the mark, shake well, and use this as the test solution. GC detection was performed according to the Chinese Light Industry Standard QB / T 4424-2012. The content was calculated by area normalization and then compared with the DSC method. The results are shown in Table 4. The ambroxol contents of batches 2383311 and 2310181 were 90.9% and 91.5%, respectively, which are greater than 90%. The ambroxol content of batch 2312221 was 42.5%, which is less than 90%. This indicates that the two detection methods have good consistency in determining the ambroxol content.
[0084] Therefore, it can be seen that differential scanning calorimetry (DSC) can be used for the determination of ambroxol content, and thus for the quality control of ambroxol. DSC has advantages such as speed, efficiency, simple operation, and good reproducibility. The establishment of this method provides a rapid and efficient analytical method for the content control of ambroxol, and provides reference data for the quality monitoring of ambroxol.
[0085] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.
Claims
1. A method for determining ambroxol, characterized in that, The method includes: The ambergris sample was determined by differential scanning calorimetry.
2. The method as described in claim 1, characterized in that, The method includes a method for determining ambroxol content.
3. The method as described in claim 1, characterized in that, The differential scanning calorimetry is performed on a differential scanning calorimeter, whose operating parameters include a heating range of 100-320℃ and a heating rate of 10℃ / min.
4. The method as described in claim 2, characterized in that, The operating parameters of the differential scanning calorimeter include the following: Close the oxygen valve, open the nitrogen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the drying gas flow rate to 140-160 ml / min, set the nitrogen flow rate to 45-55 ml / min, weigh the ambergris sample and place it in the sample position of the instrument, while the reference position of the instrument is the blank control; the heating range is 100-320℃, and the heating rate is 10℃ / min.
5. The method as described in claim 2, characterized in that, The operating parameters of the differential scanning calorimeter include the following: Close the oxygen valve, open the nitrogen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the drying gas flow rate to 140-160 ml / min, set the nitrogen flow rate to 45-55 ml / min, weigh the ambergris sample and place it in the aluminum crucible, cover it, press it with a tablet press, poke a small hole in the lid, and place it in the sample position of the instrument. At the same time, make an empty standard aluminum crucible, poke a small hole in the aluminum lid, and place it in the reference position of the instrument. The heating range is 100-320℃, and the heating rate is 10℃ / min.
6. The method as described in claim 2, characterized in that, The operating parameters of the differential scanning calorimeter include the following: Close the oxygen valve, open the nitrogen valve, adjust the auxiliary pressure gauge to less than 0.1 MPa, adjust the drying gas flow rate to 150 ml / min, set the nitrogen flow rate to 50 ml / min, weigh the ambergris sample and place it in the aluminum crucible, cover it, press it with a tablet press, poke a small hole in the lid, and place it in the sample position of the instrument. At the same time, make an empty standard aluminum crucible, poke a small hole in the aluminum lid, and place it in the reference position of the instrument. The heating range is 100-320℃, and the heating rate is 10℃ / min.
7. The method as described in claim 1, characterized in that, The ambrosin content in ambrosin samples was determined by external standard method using ambrosin reference standard.
8. The method as described in claim 1, characterized in that, The ambergris content in ambergris samples is determined and calculated by recording the peak area and / or enthalpy of the heat flux value using differential scanning calorimetry.
9. The method as described in claim 1, characterized in that, The ambrosin content in the ambrosin sample was determined by comparing the enthalpy of the ambrosin sample with that of the ambrosin reference standard.