The whole chain quality inspection and control method of Qidan Tongmai Tablets

Abstract

The invention discloses a whole-chain quality detection and control method for Qidan Tongmai tablets. The method comprises the following steps: S1, chromatographic conditions: using octadecylsilane bonded silica gel as a filler; using acetonitrile as a mobile phase A and 0.2% formic acid aqueous solution as a mobile phase B for gradient elution; using different wavelengths for detection in different time periods to detect the quality status of the five herbs in the whole prescription and perform similarity evaluation; objectively, comprehensively and accurately evaluating the quality of the Qidan Tongmai tablets; the detection method is simple, convenient to operate, short in time consumption, and convenient for detection by staff; through research on the transmission of information through a material chain, the influence of a preparation process on the preparation quality is confirmed; a fingerprint spectrum can be used to monitor the stability of the preparation process; a reference fingerprint spectrum of the Qidan Tongmai tablets is established, which is conducive to achieving quality control of different batches of products and ensuring product uniformity.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine detection, and in particular to a full-chain quality detection and control method for Qidan Tongmai Tablets. Background Art

[0002] Qidan Tongmai Tablets are composed of five herbs, namely, Danshen, Angelica, Cinnamon, Safflower and Astragalus. According to the preparation method, Safflower is partially used as raw powder, Angelica is used as medicine after percolation extraction, and the remaining herbs are all used after decoction and extraction. The quality of Chinese herbal medicine slices is affected by factors including origin, cultivation years, picking time, origin processing, storage, etc., and is also affected by the control of the preparation process during the processing into preparations. In order to maintain the stable efficacy of different batches of Qidan Tongmai Tablets, strict internal control quality standards must be formulated.

[0003] In the existing quality standard testing process of Qidan Tongmai Tablets, the composition change rules of Qidan Tongmai Tablets from raw materials, intermediates to preparations have not been specifically explained, the quality inspection and monitoring of Qidan Tongmai Tablets is not complete, and the description of the detection change rules is not clear, which leads to greatly extended detection time for later chromatography and wavelength. Therefore, a full-chain quality inspection and control method for Qidan Tongmai Tablets is proposed. Summary of the invention

[0004] The object of the present invention is to provide a whole-chain quality detection and control method for Qidan Tongmai Tablets to solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above object, the present invention provides the following technical solution: a whole-chain quality detection and control method for Qidan Tongmai Tablets, comprising: Qidan Tongmai Tablets are composed of five herbs: Danshen, Angelica, Cinnamon Twig, Carthamus tinctorius and Astragalus membranaceus, characterized in that the whole-chain quality detection and control method for Qidan Tongmai Tablets comprises the following steps:

[0006] S1. Chromatographic conditions: octadecylsilane bonded silica gel as filler; acetonitrile as mobile phase A, 0.2% formic acid aqueous solution as mobile phase B for gradient elution: 0-50 min, A: 5%-37%, B: 95%-63%; 50-52 min, A: 37-52%, B: 63%-48%; 52-80 min, A: 52%-76%, B: 48%-24%;

[0007] S2. Segmented wavelength detection: +0~10min, wavelength is 280nm; 10~20min, wavelength is 403nm; 20~27min, wavelength is: 260nm; 27.00~32min, wavelength is 403nm; 32~80min, wavelength is: 280nm, the theoretical plate number calculated based on the peak of salvianolic acid B should be no less than 3800;

[0008] S3. Preparation of reference solution: Take an appropriate amount of salvianolic acid B reference substance, accurately weigh it, and add methanol to make a solution containing 40 μg of salvianolic acid B per 1 ml to obtain a reference solution;

[0009] S4. Preparation of test solution: Take 20 tablets of Qidan Tongmai Tablets, remove the sugar coating, accurately weigh, grind, take 0.5-1g, accurately weigh, put in a stoppered conical bottle, accurately add 25ml of 70% methanol, stopper, weigh, ultrasonically treat for 30 minutes, cool, weigh again, make up the lost weight with 70% methanol, shake well, use ash-free quantitative filtration, filter, take the filtrate to obtain the test solution;

[0010] S5. Determination: Accurately pipette 10 μl of the reference solution and the test solution respectively, inject into the liquid chromatograph, and determine to obtain the detection value;

[0011] S6. Precision test: Take the same test solution and the same injection volume for 6 consecutive times, and measure according to the experimental conditions and laws. According to the fingerprint similarity evaluation system, the test sample fingerprint and the control fingerprint are similarly calculated and measured.

[0012] S7, stability test: take the same test sample solution, inject it 5 times at different times within 38 hours, measure it according to the experimental conditions and laws, and calculate the similarity between the test sample fingerprint and the control fingerprint according to the similarity evaluation system of traditional Chinese medicine chromatographic fingerprint;

[0013] S8, reproducibility experiment, take 6 samples of the same batch number, prepare and test them according to the above S1-S5 methods, and calculate the similarity between the fingerprint of the test sample and the fingerprint of the control according to the similarity evaluation system of Chinese medicine chromatographic fingerprint;

[0014] S9. Establishing fingerprints by comparison: 10 batches of samples with different batches were selected, and the samples were tested according to the above test sample preparation and chromatographic conditions. The fingerprint similarity software 2.0 was used for evaluation, and the fingerprints were established with 16 fingerprint peaks with relatively stable peaks and retention times from different batches. Peak 10, salvianolic acid B, was designated as the S peak, and a reference spectrum was established for comparison;

[0015] S10, fingerprint peak medicinal flavor identification: weigh each medicinal flavor slice according to the proportion, prepare a single medicinal solution according to the test solution preparation method, and compare it with the control fingerprint spectrum;

[0016] S11. Fingerprint peak identification: Use the specific component reference substance contained in each medicinal material to identify each fingerprint peak of the fingerprint spectrum;

[0017] S12, material chain transfer, comparison of each drug flavor with intermediates and preparations: compare the single drug chromatograms of all drug flavors with the chromatograms of intermediates and preparations, and show the number of peaks and peak area values;

[0018] S13. Comparison between intermediates and preparations: By analyzing the number and area of ​​each fingerprint peak of the preparation, it is ensured that the 4 fingerprint peaks of Carthamus tinctorius account for about 44.4% of the total peak area; the 7 fingerprint peaks of Salvia miltiorrhiza account for 42.5% of the total peak area; the 1 fingerprint peak of Cinnamon Twig accounts for 3.3%; the 1 fingerprint peak of Astragalus accounts for 1.2%; the 1 fingerprint peak of Angelica sinensis accounts for about 0.6% of the total peak area; Peaks 1, 2, and 11 are newly generated fingerprint peaks of intermediates and preparations after extraction, and the peak area accounts for 8.0%.

[0019] Preferably, the S5 medium phase chromatograph adopts an Agilent 1260 high performance liquid chromatograph.

[0020] Preferably, in S1, acetonitrile is of chromatographic grade; and other reagents are of analytical grade.

[0021] Preferably, a 200-400 nm PDA detector is used for scanning detection during the inspection wavelength process.

[0022] Preferably, the chromatographic column in the chromatograph in S5 is selected from one or more of a Krosimasil C18 column (5 μm, 4.6×250 mm) chromatographic column, a Shimadzu Inert Sustain C18 (5 μm, 4.6×250 mm) chromatographic column, and a Shiseido CAPCELL PAK MG C18 (5 μm, 4.6×250 mm) chromatographic column.

[0023] Preferably, part of safflower powder is used as medicine, angelica is used as medicine after percolation extraction, and the remaining medicinal ingredients are used as medicine after decoction in water.

[0024] Preferably, during the wavelength detection process of Qidan Tongmai Tablets, the optimal absorption wavelength of the effective ingredient of safflower is >400nm, the optimal absorption wavelength of the calycosin glucoside in astragalus is between 250-260nm, and the optimal absorption wavelength of the effective ingredients in salvia miltiorrhiza, angelica and cinnamon twig is between 260nm-290nm.

[0025] Preferably, the ultrasonic treatment in S4 uses an ultrasonic extractor with a power of 270-300W and an ultrasonic frequency of 30-40KHz.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] In the present invention, the inspection chromatographic conditions of Qidan Tongmai Tablets are specifically defined, and wavelength detection, precision detection of reference solution and test solution, stability detection and reproducibility experimental detection are carried out under specific chromatographic conditions, and the detection data of each batch of test products are specifically obtained, and experimental comparison is carried out on the data, so that the quality of Qidan Tongmai Tablets can be objectively, comprehensively and accurately evaluated. The detection method is simple, convenient to operate, and short in time, which is convenient for detection by staff. Through the study of information transmission in the material chain, the influence of the preparation process on the preparation quality is confirmed, the stability of the preparation process can be monitored by using the fingerprint spectrum, and a reference fingerprint spectrum of Qidan Tongmai Tablets is established, which is conducive to achieving the control of the quality of different batches of products and ensuring product uniformity. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a schematic diagram of the de-elution of each mobile phase in the whole chain quality detection and control method S1 of Qidan Tongmai Tablets of the present invention;

[0029] Figure 2 It is a schematic diagram of segmented wavelength detection in the whole chain quality detection and control method S2 of Qidan Tongmai Tablets of the present invention;

[0030] Figure 3 It is a schematic diagram of the comparison of the precision spectrum in the whole chain quality detection and control method S6 of Qidan Tongmai Tablets of the present invention;

[0031] Figure 4 It is a comparative schematic diagram of stability similarity in the whole chain quality detection and control method S7 of Qidan Tongmai Tablets of the present invention;

[0032] Figure 5 It is a schematic diagram of the comparison of the repeatability similarity of the fingerprint spectrum in the whole chain quality detection and control method S8 of the Qidan Tongmai Tablets of the present invention;

[0033] Figure 6 It is the reference fingerprint spectrum in the whole chain quality detection and control method of Qidan Tongmai Tablets of the present invention;

[0034] Figure 7 It is the identification diagram of each fingerprint peak reference substance in the whole chain quality detection and control method of Qidan Tongmai Tablets of the present invention;

[0035] Figure 8 It is a comparison diagram of the chromatograms of each medicinal flavor and the preparation test sample solution in the whole chain quality detection and control method of Qidan Tongmai Tablets of the present invention;

[0036] Fig. 9 It is a comparison chart of the chromatograms of the intermediate and the preparation test sample solution in the whole chain quality detection and control method of Qidan Tongmai Tablets of the present invention;

[0037] Fig.10 The whole chain quality detection and control method of Qidan Tongmai Tablets of the present invention is Figure 6Figure 2. List of fingerprint peak identification in Chinese. DETAILED DESCRIPTION

[0038] 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.

[0039] See also Figure 1-Figure 10 , the present invention provides a technical solution:

[0040] Example 1

[0041] The whole chain quality inspection and control method of Qidan Tongmai Tablets includes: Qidan Tongmai Tablets are composed of five herbs: Danshen, Angelica, Cinnamon Twig, Carthamus tinctorius and Astragalus membranaceus; the whole chain quality inspection and control method of Qidan Tongmai Tablets includes the following steps:

[0042] S1. Chromatographic conditions: octadecylsilane bonded silica gel as filler; acetonitrile as mobile phase A, 0.2% formic acid aqueous solution as mobile phase B for gradient elution: 50 min, A: 37%, B: 63%; 52 min, A: 52%, B: 48%; 80 min, A: 76%, B: 24%;

[0043] S2, segmented wavelength detection: +0min, wavelength is 280nm; 10min, wavelength is 403nm; 20min, wavelength is: 260nm; 27.00min, wavelength is 403nm; 32, wavelength is: 280nm, the theoretical plate number calculated according to the peak of salvianolic acid B should not be less than 3800;

[0044] S3. Preparation of reference solution: Take an appropriate amount of salvianolic acid B reference substance, accurately weigh it, and add methanol to make a solution containing 40 μg of salvianolic acid B per 1 ml to obtain a reference solution;

[0045] S4. Preparation of test solution: Take 20 tablets of Qidan Tongmai Tablets, remove the sugar coating, accurately weigh, grind, take 0.5-1g, accurately weigh, put in a stoppered conical bottle, accurately add 25ml of 70% methanol, stopper, weigh, ultrasonically treat for 30 minutes, cool, weigh again, make up the lost weight with 70% methanol, shake well, use ash-free quantitative filtration, filter, take the filtrate to obtain the test solution;

[0046] S5. Determination: Accurately pipette 10 μl of the reference solution and the test solution respectively, inject into the liquid chromatograph, and determine to obtain the detection value;

[0047] S6. Precision test: Take the same test solution and the same injection volume for 6 consecutive times, and measure according to the experimental conditions and laws. According to the fingerprint similarity evaluation system, the test sample fingerprint and the control fingerprint are similarly calculated and measured.

[0048] S7, stability test: take the same test sample solution, inject it 5 times at different times within 38 hours, measure it according to the experimental conditions and laws, and calculate the similarity between the test sample fingerprint and the control fingerprint according to the similarity evaluation system of traditional Chinese medicine chromatographic fingerprint;

[0049] S8, reproducibility experiment: take 6 samples of the same batch number, prepare and test them according to the above S1-S5 methods, and calculate the similarity between the fingerprint of the test sample and the fingerprint of the control according to the similarity evaluation system of the chromatographic fingerprint of traditional Chinese medicine;

[0050] S9. Establishing fingerprints by comparison: 10 batches of samples with different batches were selected, and the samples were tested according to the above test sample preparation and chromatographic conditions. The fingerprint similarity software 2.0 was used for evaluation, and the fingerprints were established with 16 fingerprint peaks with relatively stable peaks and retention times from different batches. Peak 10, salvianolic acid B, was designated as the S peak, and a reference spectrum was established for comparison;

[0051] S10, fingerprint peak medicinal flavor identification: weigh each medicinal flavor slice according to the proportion, prepare a single medicinal solution according to the test solution preparation method, and compare it with the control fingerprint spectrum;

[0052] S11. Fingerprint peak identification: Use the specific component reference substance contained in each medicinal material to identify each fingerprint peak of the fingerprint spectrum;

[0053] S12, material chain transfer, comparison of each drug flavor with intermediates and preparations: compare the single drug chromatograms of all drug flavors with the chromatograms of intermediates and preparations, and show the number of peaks and peak area values;

[0054] S13. Comparison between intermediates and preparations: By analyzing the number and area of ​​each fingerprint peak of the preparation, it is ensured that the 4 fingerprint peaks of Carthamus tinctorius account for about 44.4% of the total peak area; the 7 fingerprint peaks of Salvia miltiorrhiza account for 42.5% of the total peak area; the 1 fingerprint peak of Cinnamon Twig accounts for 3.3%; the 1 fingerprint peak of Astragalus accounts for 1.2%; the 1 fingerprint peak of Angelica sinensis accounts for about 0.6% of the total peak area; Peaks 1, 2, and 11 are newly generated fingerprint peaks of intermediates and preparations after extraction, and the peak area accounts for 8.0%.

[0055] Specifically, the S5 medium phase chromatograph adopts Agilent 1260 high performance liquid chromatograph.

[0056] Specifically, in S1, acetonitrile is of chromatographic grade; other reagents are of analytical grade.

[0057] Specifically, during the wavelength inspection process, a 200-400 nm PDA detector is used for scanning detection.

[0058] Specifically, one or more of Shimadzu Inert Sustain C18 (5um, 4.6×250mm) chromatographic columns; Shiseido CAPCELL PAKMG C18 (5μm, 4.6X250mm) chromatographic columns.

[0059] Specifically, part of the safflower powder is used as medicine, the angelica is used as medicine after percolation extraction, and the remaining medicinal flavors are used as medicine after decoction in water.

[0060] Specifically, during the wavelength detection process of Qidan Tongmai Tablets, the optimal absorption wavelength of the active ingredient of safflower is >400nm, the optimal absorption wavelength of the calycosin glucoside in astragalus is between 250 and 260nm respectively, and the optimal absorption wavelength of the active ingredients in salvia miltiorrhiza, angelica and cinnamon twig is between 260nm.

[0061] Specifically, the ultrasonic treatment in S4 uses an ultrasonic extractor with a power of 270-300W and an ultrasonic frequency of 30-40KHz.

[0062] Example 2

[0063] The whole chain quality inspection and control method of Qidan Tongmai Tablets includes: Qidan Tongmai Tablets are composed of five herbs: Danshen, Angelica, Cinnamon Twig, Carthamus tinctorius and Astragalus membranaceus; the whole chain quality inspection and control method of Qidan Tongmai Tablets includes the following steps:

[0064] S1. Chromatographic conditions: octadecylsilane bonded silica gel as filler; acetonitrile as mobile phase A, 0.2% formic acid aqueous solution as mobile phase B for gradient elution: 42 min, A: 32%, B: 67%; 50 min, A: 51%, B: 50%; 70 min, A: 60%, B: 44%;

[0065] S2, segmented wavelength detection: +7min, wavelength is 280nm; 15min, wavelength is 403nm; 24min, wavelength is: 260nm; 28min, wavelength is 403nm; 44min, wavelength is: 280nm, the theoretical plate number calculated based on the peak of salvianolic acid B should be no less than 3800;

[0066] S3. Preparation of reference solution: Take an appropriate amount of salvianolic acid B reference substance, accurately weigh it, and add methanol to make a solution containing 40 μg of salvianolic acid B per 1 ml to obtain a reference solution;

[0067] S4. Preparation of test solution: Take 20 tablets of Qidan Tongmai Tablets, remove the sugar coating, accurately weigh, grind, take 0.8, accurately weigh, put in a stoppered conical bottle, accurately add 25 ml of 70% methanol, stopper, weigh, ultrasonically treat for 30 minutes, cool, weigh again, make up the lost weight with 70% methanol, shake well, use ash-free quantitative filtration, filter, take the filtrate to obtain the test solution;

[0068] S5. Determination: Accurately pipette 10 μl of the reference solution and the test solution respectively, inject into the liquid chromatograph, and determine to obtain the detection value;

[0069] S6. Precision test: Take the same test solution and the same injection volume for 6 consecutive times, and measure according to the experimental conditions and laws. According to the fingerprint similarity evaluation system, the test sample fingerprint and the control fingerprint are similarly calculated and measured.

[0070] S7, stability test: take the same test sample solution, inject it 5 times at different times within 38 hours, measure it according to the experimental conditions and laws, and calculate the similarity between the test sample fingerprint and the control fingerprint according to the similarity evaluation system of traditional Chinese medicine chromatographic fingerprint;

[0071] S8, reproducibility experiment: take 6 samples of the same batch number, prepare and test them according to the above S1-S5 methods, and calculate the similarity between the fingerprint of the test sample and the fingerprint of the control according to the similarity evaluation system of the chromatographic fingerprint of traditional Chinese medicine;

[0072] S9. Establishing fingerprints by comparison: 10 batches of samples with different batches were selected, and the samples were tested according to the above test sample preparation and chromatographic conditions. The fingerprint similarity software 2.0 was used for evaluation, and the fingerprints were established with 16 fingerprint peaks with relatively stable peaks and retention times from different batches. Peak 10, salvianolic acid B, was designated as the S peak, and a reference spectrum was established for comparison;

[0073] S10, fingerprint peak medicinal flavor identification: weigh each medicinal flavor slice according to the proportion, prepare a single medicinal solution according to the test solution preparation method, and compare it with the control fingerprint spectrum;

[0074] S11. Fingerprint peak identification: Use the specific component reference substance contained in each medicinal material to identify each fingerprint peak of the fingerprint spectrum;

[0075] S12, material chain transfer, comparison of each drug flavor with intermediates and preparations: compare the single drug chromatograms of all drug flavors with the chromatograms of intermediates and preparations, and show the number of peaks and peak area values;

[0076] S13. Comparison between intermediates and preparations: By analyzing the number and area of ​​each fingerprint peak of the preparation, it is ensured that the 4 fingerprint peaks of Carthamus tinctorius account for about 44.4% of the total peak area; the 7 fingerprint peaks of Salvia miltiorrhiza account for 42.5% of the total peak area; the 1 fingerprint peak of Cinnamon Twig accounts for 3.3%; the 1 fingerprint peak of Astragalus accounts for 1.2%; the 1 fingerprint peak of Angelica sinensis accounts for about 0.6% of the total peak area; Peaks 1, 2, and 11 are newly generated fingerprint peaks of intermediates and preparations after extraction, and the peak area accounts for 8.0%.

[0077] Specifically, the S5 medium phase chromatograph adopts Agilent 1260 high performance liquid chromatograph.

[0078] Specifically, in S1, acetonitrile is of chromatographic grade; other reagents are of analytical grade.

[0079] Specifically, a 300 nm PDA detector is used for scanning detection during the wavelength inspection process.

[0080] Specifically, one or more of Shimadzu Inert Sustain C18 (5um, 4.6×250mm) chromatographic columns; Shiseido CAPCELL PAKMG C18 (5μm, 4.6X250mm) chromatographic columns.

[0081] Specifically, part of the safflower powder is used as medicine, the angelica is used as medicine after percolation extraction, and the remaining medicinal flavors are used as medicine after decoction in water.

[0082] Specifically, during the wavelength detection process of Qidan Tongmai Tablets, the optimal absorption wavelength of the active ingredient of safflower is >400nm, the optimal absorption wavelength of the calycosin glucoside in astragalus is between 255nm, and the optimal absorption wavelength of the active ingredients in salvia miltiorrhiza, angelica and cinnamon twig is between 270nm.

[0083] Specifically, the ultrasonic treatment in S4 uses an ultrasonic extractor with a power of 270-300W and an ultrasonic frequency of 35KHz.

[0084] Example 3

[0085] The whole chain quality inspection and control method of Qidan Tongmai Tablets includes: Qidan Tongmai Tablets are composed of five herbs: Danshen, Angelica, Cinnamon Twig, Carthamus tinctorius and Astragalus membranaceus; the whole chain quality inspection and control method of Qidan Tongmai Tablets includes the following steps:

[0086] S1. Chromatographic conditions: octadecylsilane bonded silica gel as filler; acetonitrile as mobile phase A, 0.2% formic acid aqueous solution as mobile phase B for gradient elution: 50 min, A: 5%-37%, B: 63%; 52 min, A: 52%, B: 48%; 80 min, A: 76%, B: 24%;

[0087] S2, segmented wavelength detection: +10min, wavelength is 280nm; 20min, wavelength is 403nm; 27min, wavelength is: 260nm; 32min, wavelength is: 403nm; 80min, wavelength is: 280nm, the theoretical plate number calculated based on the peak of salvianolic acid B should not be less than 3800;

[0088] S3. Preparation of reference solution: Take an appropriate amount of salvianolic acid B reference substance, accurately weigh it, and add methanol to make a solution containing 40 μg of salvianolic acid B per 1 ml to obtain a reference solution;

[0089] S4. Preparation of test solution: Take 20 tablets of Qidan Tongmai Tablets, remove the sugar coating, accurately weigh, grind, take 1g, accurately weigh, put in a stoppered conical flask, accurately add 25ml of 70% methanol, stopper, weigh, ultrasonically treat for 30 minutes, cool, weigh again, make up the lost weight with 70% methanol, shake well, use ash-free quantitative filtration, filter, take the filtrate to obtain the test solution;

[0090] S5. Determination: Accurately pipette 10 μl of the reference solution and the test solution respectively, inject into the liquid chromatograph, and determine to obtain the detection value;

[0091] S6. Precision test: Take the same test solution and the same injection volume for 6 consecutive times, and measure according to the experimental conditions and laws. According to the fingerprint similarity evaluation system, the test sample fingerprint and the control fingerprint are similarly calculated and measured.

[0092] S7, stability test: take the same test sample solution, inject it 5 times at different times within 38 hours, measure it according to the experimental conditions and laws, and calculate the similarity between the test sample fingerprint and the control fingerprint according to the similarity evaluation system of traditional Chinese medicine chromatographic fingerprint;

[0093] S8, reproducibility experiment: take 6 samples of the same batch number, prepare and test them according to the above S1-S5 methods, and calculate the similarity between the fingerprint of the test sample and the fingerprint of the control according to the similarity evaluation system of the chromatographic fingerprint of traditional Chinese medicine;

[0094] S9. Establishing fingerprints by comparison: 10 batches of samples with different batches were selected, and the samples were tested according to the above test sample preparation and chromatographic conditions. The fingerprint similarity software 2.0 was used for evaluation, and the fingerprints were established with 16 fingerprint peaks with relatively stable peaks and retention times from different batches. Peak 10, salvianolic acid B, was designated as the S peak, and a reference spectrum was established for comparison;

[0095] S10, fingerprint peak medicinal flavor identification: weigh each medicinal flavor slice according to the proportion, prepare a single medicinal solution according to the test solution preparation method, and compare it with the control fingerprint spectrum;

[0096] S11. Fingerprint peak identification: Use the specific component reference substance contained in each medicinal material to identify each fingerprint peak of the fingerprint spectrum;

[0097] S12, material chain transfer, comparison of each drug flavor with intermediates and preparations: compare the single drug chromatograms of all drug flavors with the chromatograms of intermediates and preparations, and show the number of peaks and peak area values;

[0098] S13. Comparison between intermediates and preparations: By analyzing the number and area of ​​each fingerprint peak of the preparation, it is ensured that the 4 fingerprint peaks of Carthamus tinctorius account for about 44.4% of the total peak area; the 7 fingerprint peaks of Salvia miltiorrhiza account for 42.5% of the total peak area; the 1 fingerprint peak of Cinnamon Twig accounts for 3.3%; the 1 fingerprint peak of Astragalus accounts for 1.2%; the 1 fingerprint peak of Angelica sinensis accounts for about 0.6% of the total peak area; Peaks 1, 2, and 11 are newly generated fingerprint peaks of intermediates and preparations after extraction, and the peak area accounts for 8.0%.

[0099] Specifically, the S5 medium phase chromatograph adopts Agilent 1260 high performance liquid chromatograph.

[0100] Specifically, in S1, acetonitrile is of chromatographic grade; other reagents are of analytical grade.

[0101] Specifically, during the wavelength inspection process, a 400 nm PDA detector was used for scanning detection.

[0102] Specifically, one or more of Shimadzu Inert Sustain C18 (5um, 4.6×250mm) chromatographic columns; Shiseido CAPCELL PAKMG C18 (5μm, 4.6X250mm) chromatographic columns.

[0103] Specifically, part of the safflower powder is used as medicine, the angelica is used as medicine after percolation extraction, and the remaining medicinal flavors are used as medicine after decoction in water.

[0104] Specifically, during the wavelength detection process of Qidan Tongmai Tablets, the optimal absorption wavelength of the active ingredient of safflower is >400nm, the optimal absorption wavelength of the calycosin glucoside in astragalus is between 260nm, and the optimal absorption wavelength of the active ingredients in salvia miltiorrhiza, angelica and cinnamon twig is between 290nm.

[0105] Specifically, the ultrasonic treatment in S4 uses an ultrasonic extractor with a power of 300W and an ultrasonic frequency of 40KHz.

[0106] The working steps of this scheme are summarized and sorted out according to the above technical scheme: In the present invention, the inspection chromatographic conditions of Qidan Tongmai Tablets are specifically defined, and wavelength detection, precision detection of reference solution and test solution, stability detection and reproducibility experimental detection are carried out under specific chromatographic conditions. The detection data of each batch of test products are specifically obtained, and the data are experimentally compared. The quality of Qidan Tongmai Tablets can be objectively, comprehensively and accurately evaluated. The detection method is simple, easy to operate, and time-saving, which is convenient for staff to detect. Through the study of information transmission in the material chain, the influence of the preparation process on the preparation quality is confirmed. The stability of the preparation process can be monitored by using the fingerprint spectrum. A control fingerprint spectrum of Qidan Tongmai Tablets is established, which is conducive to the control of the quality of different batches of products and ensures product uniformity.

[0107] Parts not involved in the present invention are the same as the prior art or can be implemented by the prior art. Although the embodiments of the present invention have been shown and described, it is understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A full-chain quality inspection and control method for Qidan Tongmai Tablets, comprising the quality inspection and control of the five herbs of the Qidan Tongmai Tablets, namely, Danshen, Angelica, Cinnamon Twig, Carthamus tinctorius and Astragalus membranaceus, characterized in that: The control of drug taste quality, preparation process control and product quality is achieved through fingerprint technology, including the following steps: S1. Chromatographic conditions: octadecylsilane bonded silica gel as filler; acetonitrile as mobile phase A, 0.2% formic acid aqueous solution as mobile phase B for gradient elution: 0-50 min, A: 5%-37%, B: 95%-63%; 50-52 min, A: 37-52%, B: 63%-48%; 52-80 min, A: 52%-76%, B: 48%-24%; S2. Segmented wavelength detection: 0-10min, wavelength is 280nm; 10-20min, wavelength is 403nm; 20-27min, wavelength is 260nm; 27.00-32min, wavelength is 403nm; 32-80min, wavelength is 280nm, the theoretical plate number calculated based on the salvianolic acid B peak should be no less than 3800; S3. Preparation of reference solution: Take an appropriate amount of salvianolic acid B reference substance, accurately weigh it, and add methanol to make a solution containing 40 μg of salvianolic acid B per 1 ml to obtain a reference solution; S4. Preparation of test solution: Take 20 tablets of Qidan Tongmai Tablets, remove the sugar coating, accurately weigh, grind, take 0.5-1g, accurately weigh, put in a stoppered conical flask, accurately add 25ml of 70% methanol, stopper, weigh, ultrasonically treat for 30 minutes, cool, weigh again, make up the lost weight with 70% methanol, shake well, use ash-free quantitative filtration, filter, take the filtrate to obtain the test solution; S5. Determination: Accurately pipette 10 μl of the reference solution and the test solution respectively, inject into the liquid chromatograph, and determine to obtain the detection value; S6. Precision test: Take the same test solution and the same injection volume for 6 consecutive times, and measure according to the experimental conditions and laws. According to the fingerprint similarity evaluation system, the test sample fingerprint and the control fingerprint are similarly calculated and measured. S7, stability test: take the same test sample solution, inject it 5 times at different times within 38 hours, measure it according to the experimental conditions and laws, and calculate the similarity between the test sample fingerprint and the control fingerprint according to the similarity evaluation system of traditional Chinese medicine chromatographic fingerprint; S8, reproducibility experiment, take 6 samples of the same batch number, prepare and test them according to the above S1-S5 methods, and calculate the similarity between the fingerprint of the test sample and the fingerprint of the control according to the similarity evaluation system of Chinese medicine chromatographic fingerprint; S9. Establishing fingerprints by comparison: 10 batches of samples with different batches were selected, and the samples were tested according to the above test sample preparation and chromatographic conditions. The fingerprint similarity software 2.0 was used for evaluation, and the fingerprints were established with 16 fingerprint peaks with relatively stable peaks and retention times from different batches. Peak 10, salvianolic acid B, was designated as the S peak, and a reference spectrum was established for comparison; S10, fingerprint peak medicinal flavor identification: weigh each medicinal flavor slice according to the proportion, prepare a single medicinal solution according to the test solution preparation method, and compare it with the control fingerprint spectrum; S11. Fingerprint peak identification: Use the specific component reference substance contained in each medicinal material to identify each fingerprint peak of the fingerprint spectrum; S12, material chain transfer, comparison of each drug flavor with intermediates and preparations: compare the single drug chromatograms of all drug flavors with the chromatograms of intermediates and preparations, and show the number of peaks and peak area values; S13. Comparison between intermediates and preparations: By analyzing the number and area of ​​each fingerprint peak of the preparation, it is ensured that the 4 fingerprint peaks of Carthamus tinctorius account for about 44.4% of the total peak area; the 7 fingerprint peaks of Salvia miltiorrhiza account for 42.5% of the total peak area; the 1 fingerprint peak of Cinnamon twig accounts for 3.3%; the 1 fingerprint peak of Astragalus membranaceus accounts for 1.2%; the 1 fingerprint peak of Angelica sinensis accounts for about 0.6% of the total peak area; Peaks 1, 2, and 11 are newly generated fingerprint peaks of intermediates and preparations after extraction, and the peak area accounts for 8.0%.

2. The whole chain quality detection and control method of Qidan Tongmai Tablets according to claim 1, characterized in that: The S5 medium phase chromatograph adopts Agilent 1260 high performance liquid chromatograph.

3. The whole chain quality detection and control method of Qidan Tongmai Tablets according to claim 1, characterized in that: In S1, acetonitrile was of chromatographic grade; other reagents were of analytical grade.

4. The whole chain quality detection and control method of Qidan Tongmai Tablets according to claim 1, characterized in that: During the wavelength inspection process, a 200-400nm PDA detector was used for scanning detection.

5. The whole chain quality detection and control method of Qidan Tongmai Tablets according to claim 1, characterized in that: The chromatographic column in the chromatograph in the S5 is selected from one or more of Krosimasil C18 column, with a specification of 5 μm, 4.6×250 mm; Shimadzu Inert Sustain C18, with a specification of 5 μm, 4.6×250 mm; and Shiseido CAPCELL PAK MG C18, with a specification of 5 μm, 4.6×250 mm.

6. The whole chain quality detection and control method of Qidan Tongmai Tablets according to claim 1, characterized in that: Part of the safflower powder is used as medicine, angelica is used as medicine after percolation extraction, and the rest of the medicinal flavors are used as medicine after being boiled in water and extracted.

7. The whole chain quality detection and control method of Qidan Tongmai Tablets according to claim 1, characterized in that: During the wavelength detection process of Qidan Tongmai Tablets, the optimal absorption wavelength of the active ingredient of safflower is >400nm, the optimal absorption wavelength of the calycosin glucoside in astragalus is between 250-260nm, and the optimal absorption wavelength of the active ingredients in salvia miltiorrhiza, angelica and cinnamon twig is between 260nm-290nm.

8. The whole chain quality detection and control method of Qidan Tongmai Tablets according to claim 1, characterized in that: The ultrasonic treatment in S4 adopts an ultrasonic extractor with a power of 270-300W and an ultrasonic frequency of 30-40KHz.

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