CN115493917A - Dissolution curve determination method of Ruuggoli tablets - Google Patents

Dissolution curve determination method of Ruuggoli tablets Download PDF

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CN115493917A
CN115493917A CN202211020727.7A CN202211020727A CN115493917A CN 115493917 A CN115493917 A CN 115493917A CN 202211020727 A CN202211020727 A CN 202211020727A CN 115493917 A CN115493917 A CN 115493917A
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dissolution
solution
medium
potassium dihydrogen
dihydrogen phosphate
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王英蛟
熊玲
庞晓星
乔智涛
陈洪
王颖
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Chengdu Shuoder Pharmaceutical Co ltd
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Abstract

The invention belongs to the technical field of drug analysis, and provides a dissolution curve determination method of Ruugeli tablets with good durability and reproducibility and distinguishing force, wherein a phosphate buffer solution with pH5.6 is used as a dissolution medium in the dissolution curve method, so that the problem that the dissolution method in the prior art cannot meet the requirement of comparing the similarity of dissolution curves by adopting a similarity factor (f 2) method in the guiding principle of 'determination of dissolution curves and comparison guiding principle of common oral solid preparations', and thus the screening of the simulated pharmaceutical process of the Ruugeli tablets and the evaluation of the in-vitro consistency are influenced is solved.

Description

Dissolution curve determination method of Ruuggoli tablets
Technical Field
The invention belongs to the technical field of drug analysis, and particularly relates to a dissolution curve determination method of Ruugoli tablets.
Background
Reluggolix (Relugolix) was the first oral gonadotropin releasing hormone (GnRH) receptor antagonist to be used in the treatment of endometriosis and advanced prostate cancer. Is a small molecular gonadotropin-releasing hormone (GnRH) receptor antagonist, and is used for treating hysteromyoma and relieving symptoms in 2019. Since it rapidly achieves simultaneous suppression of LH and FSH release from the pituitary in a short period of time and has been shown by several clinical phase i and phase ii studies to reduce testosterone levels, it is later approved for the treatment of advanced prostate cancer.
According to a Biopharmaceutics Classification System (BCS), ruugeli is classified into BCS IV, the BCS IV belongs to low-solubility and low-permeability medicines, the dissolution and dissolution of the medicines directly influence the absorption of the medicines, the dissolution media with not less than 3 pH values (at least pH values 1.2, 4.5 and 6.8) are recommended to be selected for dissolution curve investigation according to questions (research suggestions) of dissolution curve determination and comparison guide principles of common oral solid preparation and guide principles (trial) of chemical medicine pharmaceutical change research technology in the market, some standard media (media used in registration standards) may contain a small amount of surfactant, other media are not recommended to be added except the standard media, and for the medicines with solubility influenced by pH values, investigation in the dissolution media with more pH values may be required. Ruuggol as a drug with solubility greatly influenced by pH value (the solubility is lower when the pH value is larger), the drug is dissolved out too fast under the medium conditions of pH1.2 and pH4.5, and the dissolution rate is over 85 percent in 15 minutes; the dissolution is too slow under the medium condition of pH6.8, and can not reach 85% in 6 hours; at present, a referred dissolution curve determination medium is only citric acid buffer salt with pH value of 5.5 suggested in an FDA evaluation report, however, under the condition of the medium, the dissolution rate of the Ruugeli reference preparation in 15 minutes reaches 85%, and the evaluation cannot be carried out by referring to a similar factor (f 2) method provided in the general oral solid preparation dissolution curve determination and comparison guiding principle, so that the evaluation of the in-vitro consistency of the imitation drugs is influenced. Therefore, the development of a dissolution profile having a discriminative power is of great importance for guidance of the development of a Ruugeli mimetic preparation, evaluation of the consistency of the quality between batches of the preparation, evaluation of the consistency of the quality and the therapeutic effect before and after the process change of a drug formulation, and the like.
Disclosure of Invention
The invention provides a dissolution curve determination method of Ruugeli tablets with good durability and reproducibility and differentiated force by investigating dissolution curves of different pH media, and aims to solve the problem that the dissolution method in the prior art cannot meet the requirement of comparing the similarity of dissolution curves by adopting a similarity factor (f 2) method in the guiding principle of 'determination of dissolution curves and comparison guiding principle of common oral solid preparations', so that the screening of the simulated pharmaceutical process of the Ruugeli tablets and the evaluation of in-vitro consistency are influenced.
In order to achieve the above purpose, the invention provides the following technical scheme:
a dissolution curve determination method of Ruuggolide tablets comprises the following steps:
step (1): preparing a phosphate buffer solution with pH of 5.6 as a dissolution medium;
step (2): measuring the dissolution medium in the step (1), placing in a dissolution cup, heating, adding Ruuggolin tablets in the dissolution cup under stirring, timing, taking out dissolution liquid at different dissolution time points, detecting the dissolution amount, and establishing a dissolution curve according to the dissolution amount and the dissolution time.
Further, the dissolution medium in the step (1) comprises a mixed solution of potassium dihydrogen phosphate, a pH value regulator and water, wherein the pH value regulator is sodium hydroxide.
Further, the specific preparation method of the dissolution medium in the step (1) is that 27.200 plus or minus 0.100g of potassium dihydrogen phosphate is weighed, and 90ml to 97ml of sodium hydroxide solution is weighed and added into 4L of degassed purified water for dissolution.
Furthermore, the specific preparation method of the dissolution medium in the step (1) is to weigh 27.200 ± 0.100g of potassium dihydrogen phosphate, and weigh 90-97ml of 0.1mol/L sodium hydroxide solution (weigh 4.000 ± 0.004g of sodium hydroxide in a 1L measuring flask, dissolve in degassed purified water and dilute to the scale), and add into 4L of degassed purified water to dissolve, and the volume of the added 0.1mol/L sodium hydroxide solution is preferably 94ml.
Furthermore, the dosage of the dissolution medium in the step (2) is 900 mL/cup, the stirring speed is 40-75rpm/min, preferably 50rpm/min, and the dissolution medium temperature is 37 +/-0.5 ℃.
Further, the different dissolution time points in the step (2) are 5, 10, 15, 20, 30, 45, 60, 90 and 120min.
Further, the method for detecting the elution amount in the step (2) is high performance liquid chromatography.
Furthermore, in the detection process of the high performance liquid chromatography, the adopted chromatographic column is a C8 chromatographic column, and preferably an Agilent SB-C8 chromatographic column.
Further, in the detection process of the high performance liquid chromatography, the adopted mobile phase comprises a phosphate buffer solution and acetonitrile, and the volume ratio of the phosphate buffer solution to the acetonitrile is 3; the pH value of the phosphate buffer solution is 2.2 +/-0.1, and the phosphate buffer solution with the pH value of 2.2 is preferred; the volume ratio of the phosphate buffer solution to the acetonitrile is 3; preferably, the pH of the phosphate buffer is adjusted by phosphoric acid.
The phosphate buffer solution is a potassium dihydrogen phosphate solution, the potassium dihydrogen phosphate solution comprises potassium dihydrogen phosphate and water, and the molar volume ratio of the potassium dihydrogen phosphate to the water is (0.01-0.03).
Furthermore, in the detection process of the high performance liquid chromatography, acetonitrile and 0.02mol/L potassium dihydrogen phosphate solution are used as mobile phases, and the pH value of the 0.02mol/L potassium dihydrogen phosphate solution is adjusted to 2.2 +/-0.1 by phosphoric acid, wherein the volume ratio of the acetonitrile to the 0.02mol/L potassium dihydrogen phosphate solution is 3.
Further, in the detection process of the high performance liquid chromatography, the column temperature of a chromatographic column is 40 ℃; the detection wavelength was 291nm, the injection volume was 5. Mu.l, and the flow rate was 1.0ml/min.
Further, the chromatographic conditions of the high performance liquid chromatography are as follows:
a chromatographic column: agilent SB-C8 chromatographic column; detection wavelength: 291nm; the flow rate is 1.0ml/min; sample introduction volume: 5 mu l of the solution; column temperature: 40 ℃; mobile phase: a mixed solution of 0.02mol/L potassium dihydrogen phosphate solution and acetonitrile, wherein the pH value of the 0.02mol/L potassium dihydrogen phosphate solution is adjusted to 2.2 +/-0.1 by phosphoric acid, and the volume ratio of the 0.02mol/L potassium dihydrogen phosphate solution to the acetonitrile is 3.
Furthermore, the preparation method of the mobile phase comprises the steps of dissolving 2.72g of monopotassium phosphate in 1L of purified water, adjusting the pH to 2.2 +/-0.1 by using phosphoric acid, filtering to obtain a phosphate buffer solution, and mixing acetonitrile with the phosphate buffer solution to ensure that the volume ratio of the acetonitrile to the acetonitrile is 3.
Further, in the detection process of the high performance liquid chromatography, the preparation method of the test solution comprises the following steps: and (3) respectively taking 10ml of the dissolution liquid at different time points in the step (2), filtering by using a 0.45-micrometer filter membrane, discarding 5-7ml of the primary filtrate, and taking the subsequent filtrate as a test solution.
Furthermore, the preparation method of the test solution comprises the following steps: respectively taking 10ml of the dissolution liquid at different time points in the step (2), timely replenishing 10ml of dissolution medium, filtering the dissolution liquid with PES (0.45 mu m,25 mm) filter head by the taken 10ml of dissolution liquid, discarding 6ml of primary filtrate, and taking the subsequent filtrate as a test solution.
Furthermore, although the filter head PES (0.45 μm,25 mm) used in the leaching solution is a commonly used filter head in a water system, in the application process, the leaching amount obtained is abnormally increased after the same filter head is continuously used for a long time, which indicates that the filter head is damaged or the Ruugeli adsorbed on the filter membrane is redissolved at the moment, and a preferable method is to replace the filter head after each time point is taken out.
In the step (2), the conventional dissolution process may be referred to as the dissolution process, for example, the paddle method is used as the dissolution process, and the dissolution apparatus refers to the second method 0931, the fourth general rule in 2020 edition of Chinese pharmacopoeia.
Further, the high performance liquid chromatography can be carried out by referring to the conventional procedures in the prior art, and preferably, the quantitative analysis is carried out by adopting an external standard method.
Furthermore, the dissolution curve determination method of the rilogeli tablet provided by the invention comprises the following steps:
step (1): 27.200 +/-0.100 g of monopotassium phosphate is weighed, 90ml-97ml of sodium hydroxide solution is weighed and added into 4L of degassed purified water for dissolution;
step (2): adopting a paddle method, respectively measuring 900ml of dissolution medium in the step (1), placing the dissolution medium in a dissolution cup, setting the temperature of the dissolution medium to be 37 +/-0.5 ℃, stirring at 50rpm/min, putting Ruugeli tablets in the dissolution cup, timing, respectively taking 10ml of dissolution liquid after 5, 10, 15, 20, 30, 45, 60, 90 and 120min, timely replenishing 10ml of dissolution medium, filtering the taken 10ml of dissolution liquid by using a 0.45 mu m filter membrane, discarding 5-7ml of primary filtrate, taking subsequent filtrate as a test solution, detecting the dissolution amount by adopting a high performance liquid chromatography, and establishing a dissolution curve according to the dissolution amount and the dissolution time;
furthermore, the dissolution curve determination method of the Ruugolii tablet comprises the following steps:
step (1): 27.200 +/-0.100 g of monopotassium phosphate is weighed, 90ml-97ml of sodium hydroxide solution is weighed and added into 4L of degassed purified water for dissolution;
step (2): adopting a paddle method, respectively measuring 900ml of dissolution medium in the step (1), placing the dissolution medium in a dissolution cup, setting the temperature of the dissolution medium to be 37 +/-0.5 ℃, stirring at 50rpm/min, putting Ruugeli tablets in the dissolution cup, timing, respectively taking 10ml of dissolution liquid after 5, 10, 15, 20, 30, 45, 60, 90 and 120min, timely replenishing 10ml of dissolution medium, filtering the taken 10ml of dissolution liquid by using a 0.45 mu m filter membrane, discarding 5-7ml of primary filtrate, taking subsequent filtrate as test solution, detecting the dissolution amount by adopting a high performance liquid chromatography, and establishing a dissolution curve according to the dissolution amount and the dissolution time;
the chromatographic conditions of the high performance liquid chromatography are as follows: a chromatographic column: an Agilent SB-C8 chromatographic column; detection wavelength: 291nm; the flow rate is 1.0ml/min; sample introduction volume: 5 mu l of the solution; column temperature: 40 ℃; mobile phase: and (2) a mixed solution of 0.02mol/L potassium dihydrogen phosphate solution and acetonitrile, wherein the pH value of the 0.02mol/L potassium dihydrogen phosphate solution is adjusted to 2.2 by using phosphoric acid, and the volume ratio of the 0.02mol/L potassium dihydrogen phosphate solution to the acetonitrile is 3.
Compared with the prior art, the invention has the following beneficial effects:
(1) The invention solves the defects that the conventional dissolution curve in the prior art has no discrimination, and the difference between the dissolution behaviors of the Ruugolii tablet imitation preparation and the original preparation in vitro cannot be accurately measured, the technical scheme of the invention is applied, the dissolution speed of the Ruugolii tablet is obviously improved, the dissolution amount in 15 minutes is less than 85 percent, the dissolution amount in 2 hours is more than 85 percent, the requirement of common oral solid preparation dissolution curve determination and comparison guide principle on adopting a similarity factor (f 2) method to compare the similarity of the dissolution curves is met, the obtained dissolution curve can be used for process screening and in vitro consistency evaluation, the internal quality of the Ruugolii tablet can be better reflected, the in vivo and in vitro correlation is good, and the invention has important significance for improving the efficiency of bioequivalence test, accelerating the research and development process, enriching the domestic drug supply and reducing the medical cost.
(2) The method has the characteristics of scientificity, durability, reproducibility and the like, can effectively distinguish the influence of different prescriptions and process variables on the in-vitro release of the Ruugeli tablets, can be used for evaluating the quality consistency of the imitation drugs and the original drugs, and can also provide guarantee for the quality consistency among drug batches so as to guarantee the quality of the drugs.
Drawings
Fig. 1 is a dissolution profile of three batches of rilogeli tablet reference formulation and two batches of homemade formulation provided in example 1 of the present invention.
Detailed Description
The method of the present invention is described below with reference to specific examples to make it easier to understand and understand the technical solution of the present invention, but the present invention is not limited thereto. The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
In the following examples, referring to "determination of dissolution curve and comparative guideline for general oral solid preparation", a similarity factor method is used to calculate a similarity factor (f 2) using dissolution amount data of a reference preparation and a home-made preparation at different time points, and the similarity factor (f 2) is used to evaluate the similarity between the reference preparation and the home-made preparation.
The similarity factor (f 2) is calculated by the formula:
Figure BDA0003813915960000041
wherein Rt is the average dissolution amount of a reference preparation at t time; tt is the average dissolution amount of the self-made sample at the time t; n is the number of sampling time points.
Example 1
(1) Ruuggoli tablet sample
Reference preparations (batch number: S11399A, T04328A, T05195A)
Self-made preparation (batch: 22070402, 220705)
(2) The dissolution curve measuring method comprises the following steps:
1. dissolution conditions
The pulp method is adopted, the volume of the dissolution medium is 900 ml/cup, the rotating speed is 50rpm/min, and the temperature of the dissolution medium is 37 +/-0.5 ℃.
2. Dissolution medium preparation
27.200 +/-0.100 g of monopotassium phosphate is weighed, and 90-97ml of 0.1mol/L sodium hydroxide solution (3.996-4.004 g of sodium hydroxide is weighed in a 1L measuring flask, dissolved in degassed purified water and diluted to scale) is added into 4L of degassed purified water for dissolution.
3. Detection method and solution preparation
Detecting the elution amount by adopting a high performance liquid chromatography, wherein the chromatographic conditions are as follows: agilent SB-C8 chromatographic column; detection wavelength: 291nm; the flow rate is 1.0ml/min; sample introduction volume: 5 mu l of the solution; column temperature: at 40 ℃. Mobile phase: a mixed solution of 0.02mol/L potassium dihydrogen phosphate solution and acetonitrile (pH adjusted to 2.2. + -. 0.1 with phosphoric acid) (3.
Preparation of a mobile phase: dissolving 2.72g of monopotassium phosphate in 1L of purified water, adjusting the pH to 2.2 +/-0.1 by using phosphoric acid, filtering to obtain a phosphate buffer solution, and mixing acetonitrile with the phosphate buffer solution to ensure that the volume ratio of the phosphate buffer solution to the acetonitrile is 3.
Preparing a reference substance solution: precisely weighing 13.33mg of Ruugeli reference substance into a 100ml measuring flask, adding 5ml of acetonitrile, ultrasonically dissolving, and adding a dissolution medium to dilute to scale.
Test solution: adopting a paddle method, respectively measuring 900 ml/cup of prepared dissolution medium, placing the dissolution medium in a dissolution cup, setting the temperature of the dissolution medium at 37 +/-0.5 ℃, stirring at 50rpm/min, putting Ruugeli tablets in the dissolution cup, respectively taking 10ml of dissolution liquid out at 5, 10, 15, 20, 30, 45, 60, 90 and 120min, then supplementing the volume of the dissolution medium to 10ml, adopting a PES (0.45 mu m and 25 mm) filter head for filtration, discarding 6ml of primary filtrate, taking continuous filtrate as a sample solution directly, and replacing the filter head once after sampling at each time point.
The determination method comprises the following steps: and (5) respectively injecting the reference substance solution and the test solution into a high performance liquid chromatograph, and calculating the dissolution amount.
(3) Results of measurement of dissolution Curve
The dissolution curves of three reference batches of the formulation (batches: S11399A, T04328A and T05195A) and two self-made batches of the formulation (batches: 22070402 and 220705) were measured according to the above measurement method, the specific dissolution curve measurement results (dissolution amount and relative standard deviation) are shown in Table 1, and the dissolution curves are shown in figure 1. And calculating a similarity factor (f 2) by referring to 'determination of dissolution curve of common oral solid preparation and comparative guiding principle' for evaluating the similarity between the reference preparation and the self-made preparation, and the result is shown in table 2.
Table 1 dissolution profile data for each batch of formulations
Figure BDA0003813915960000061
TABLE 2 similarity factor (f 2) for each batch of preparations
Batches of T04328A T05195A S11399A
22070402 30 34 31
220705 42 50 45
From the first table, it can be seen that the dissolution curve data of the three reference batches of the formulation, whether the dissolution amount or the relative standard deviation (RSD%), satisfy the data requirement of the "determination of dissolution curve and comparison guiding principle of common oral solid formulation" for similarity comparison using the similarity factor (f 2).
It can be seen from table two that the similarity factors (f 2) of the home-made preparations 22070402 batches are obviously smaller than 220705 batches, which shows that the dissolution curve method has stronger distinguishing capability, can distinguish the difference between different prescriptions, and has the uniformity and the repeatability which meet the requirements, which shows that the method is suitable for evaluating the difference between different batches of the Ruugolii tablets and the difference of the in-vitro dissolution behavior between the Ruugolii tablets and the original preparation, can evaluate the difference of the in-vivo dissolution behavior between the Ruugolii tablets and the original preparation, makes predictions for in-vivo bioequivalence tests, and improves the success rate of the bioequivalence tests.
Test example 1 dissolution Medium pH examination test
Rilogeli tablet samples: self-made preparation (220117 batch)
According to the measurement method described in example 1, using the self-made preparation (220117 lot) as a sample, the dissolution data under the dissolution medium conditions of different pH were measured by examining 87ml, 90ml, 92ml, 95ml and 97ml respectively by changing the addition volume of 0.1mol/L sodium hydroxide solution in the dissolution medium preparation method of example 1 and measuring the pH of the dissolution medium, and the results are shown in Table III. And the similarity factor (f 2) of the dissolution curves obtained for the other addition volumes was calculated, using an addition volume of 92ml (first measurement) as standard, and the results are given in table four.
TABLE III dissolution data under different pH dissolution media conditions
Figure BDA0003813915960000071
TABLE four similar factors under different pH dissolution media conditions
Volume of addition 87ml 90ml 92ml (second time) 95ml 97ml
Similarity factor (f 2) 63 80 89 80 88
pH of dissolution medium 5.54 5.56 5.60 5.62 5.62
As can be seen from Table IV, when the volumes of 90, 92, 95 and 97ml are added, the pH of the dissolution medium is between 5.56 and 5.62, and the similarity factors (f 2) are all above 80; when the volume of the dissolution medium is 87ml, the pH value of the dissolution medium is 5.54, and the similarity factor (f 2) is obviously reduced to 63, which shows that the dissolution curve of the Ruugolii tablet is extremely sensitive to the tiny change of the pH value of the medium under the condition of the pH value of 5.6 medium, the pH value of the dissolution medium needs to be strictly controlled, and when the volume of 0.1mol/L sodium hydroxide is between 90ml and 97ml, a stably reproduced dissolution curve result can be obtained; when the addition volume of 0.1mol/L of sodium hydroxide is out of this range (e.g., 87ml as mentioned above), no results are obtained which correspond to the addition volumes of 90 to 97 ml.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A dissolution curve determination method of Ruuggoli tablets is characterized in that,
step (1): preparing a phosphate buffer solution with pH of 5.6 as a dissolution medium;
step (2): measuring the dissolution medium in the step (1), putting the dissolution medium into a dissolution cup, putting Ruuggolin tablets into the dissolution cup under the stirring condition, timing, taking the dissolution liquid at different dissolution time points, detecting the dissolution amount, and establishing a dissolution curve according to the dissolution amount and the dissolution time.
2. A dissolution profile determination method according to claim 1, characterized in that the dissolution medium comprises potassium dihydrogen phosphate, a pH adjusting agent, preferably sodium hydroxide, and water.
3. A dissolution profile determination method according to claim 1, wherein the dissolution medium is specifically prepared by weighing 27.200 ± 0.100g of potassium dihydrogen phosphate, and weighing 90-97ml of sodium hydroxide solution, and adding into 4L of degassed purified water for dissolution.
4. The dissolution profile measuring method according to claim 1, wherein the method for detecting the amount of dissolution in step (2) is high performance liquid chromatography.
5. The dissolution profile determination method according to claim 1, wherein the dissolution medium is used in an amount of 900 mL/cup, the stirring speed is 40-75rpm/min, preferably 50rpm/min, and the dissolution medium is at a temperature of 37 ± 0.5 ℃.
6. The dissolution profile measurement method according to claim 1, wherein the different dissolution time points are 5, 10, 15, 20, 30, 45, 60, 90, 120min.
7. The dissolution profile measurement method according to claim 4, wherein the chromatographic conditions in the HPLC detection process are as follows: the adopted chromatographic column is a C8 chromatographic column, preferably an Agilent SB-C8 chromatographic column; the temperature of the chromatographic column is 40 ℃; the detection wavelength is 291nm, the sample injection volume is 5 mul, and the flow rate is 1.0ml/min; the mobile phase is a mixed solution of phosphate buffer solution and acetonitrile, and the pH value of the phosphate buffer solution is 2.2 +/-0.1; the volume ratio of the phosphate buffer solution to the acetonitrile is 3.
8. A dissolution profile measurement method according to claim 7, wherein the phosphate buffer solution is a potassium dihydrogen phosphate solution comprising potassium dihydrogen phosphate and water in a molar volume ratio of 0.01 to 0.03.
9. The dissolution profile measurement method according to claim 4, wherein the sample solution is prepared by: respectively taking 10ml of the dissolution liquid at different time points in the step (2), filtering with a 0.45-micrometer filter membrane, discarding 5-7ml of the primary filtrate, and taking the subsequent filtrate as the test solution.
10. The dissolution profile determination method according to claim 1, comprising the steps of:
step (1): weighing 27.200 +/-0.100 g of monopotassium phosphate, weighing 90-97ml of sodium hydroxide solution, and adding the sodium hydroxide solution into 4L of degassed purified water for dissolving;
step (2): respectively measuring 900ml of the dissolution medium obtained in the step (1) by adopting a paddle method, placing the dissolution medium into a dissolution cup, setting the temperature of the dissolution medium at 37 +/-0.5 ℃, stirring at 50rpm/min, putting Ruugeli tablets into the dissolution cup, timing, respectively taking 10ml of dissolution liquid after 5, 10, 15, 20, 30, 45, 60, 90 and 120min, filtering by using a 0.45 mu m filter membrane, discarding 5-7ml of primary filtrate, taking a subsequent filtrate as a test solution, detecting the dissolution amount by adopting a high performance liquid chromatography, and establishing a dissolution curve according to the dissolution amount and the dissolution time;
the chromatographic conditions of the high performance liquid chromatography are as follows: a chromatographic column: agilent SB-C8 chromatographic column; detection wavelength: 291nm; the flow rate is 1.0ml/min; sample introduction volume: 5 mu l of the solution; column temperature: 40 ℃; mobile phase: a mixed solution of 0.02mol/L potassium dihydrogen phosphate solution and acetonitrile, wherein the pH value of the 0.02mol/L potassium dihydrogen phosphate solution is adjusted to 2.2 +/-0.1 by phosphoric acid, and the volume ratio of the 0.02mol/L potassium dihydrogen phosphate solution to the acetonitrile is 3.
CN202211020727.7A 2022-08-24 2022-08-24 Dissolution curve determination method of Ruuggoli tablets Pending CN115493917A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117129597B (en) * 2023-08-28 2024-07-12 苏州方昆医药科技有限公司 Method for detecting rui Lu Geli in plasma by HPLC-MS/MS method

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117129597B (en) * 2023-08-28 2024-07-12 苏州方昆医药科技有限公司 Method for detecting rui Lu Geli in plasma by HPLC-MS/MS method

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