CN111272918A - High performance liquid chromatography-mass spectrometry detection method for nafil medicine intermediate - Google Patents
High performance liquid chromatography-mass spectrometry detection method for nafil medicine intermediate Download PDFInfo
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Abstract
The invention discloses a high performance liquid chromatography-mass spectrometry detection method for nafil medicine intermediates, and belongs to the field of medicine detection. The method comprises the steps of measuring the tetrahydrocarboline hydrochloride serving as the traditional Chinese medicine intermediate in the food by an ultra-performance liquid chromatography tandem mass spectrometry, dissolving a sample by a 50% methanol solution, carrying out ultrasonic extraction, detecting by the liquid chromatography tandem mass spectrometry under an ESI source positive ion mode, collecting by a multi-reaction monitoring (MRM) mode, and quantifying by an external standard method. The method has the advantages of simple and convenient detection steps, strong specificity, high sensitivity and accurate and reliable detection result, and provides more reliable confirmation basis for the supervision of illegally adding chemical drugs in food and health-care food. Aiming at the current domestic lack of a related detection method of a medical intermediate tetrahydrocarboline hydrochloride, the invention fills the gap of the domestic analysis and detection method of the compound.
Description
Technical Field
The invention relates to the field of drug detection, in particular to a high performance liquid chromatography-mass spectrometry detection method of nafil pharmaceutical intermediates.
Background
At present, the national food and drug administration has issued a supplementary inspection method for illegally adding yang-strengthening medicines into various foods and health-care foods. However, under high pressure shock, the molecular weight of the patient is not allowed to be measured, and other analogs outside the range of the current standard, such as cis- (1R,3R) -1,2,3, 4-tetrahydro-1- (3, 4-methylenedioxyphenyl) -9H-pyrido [3,4-B ] are added]Indole-3-carboxylic acid methyl ester hydrochloride (abbreviation: tetrahydrocarboline hydrochloride, chemical formula: C)20H19ClN2O4CAS number: 171752-68-4), the substance is a novel tadalafil derivative, is a key intermediate for synthesizing tadalafil, is not approved to be on the market in China, and has no relevant detection method at home and abroad.
The above background disclosure is only for the purpose of assisting understanding of the inventive concept and technical solutions of the present invention, and does not necessarily belong to the prior art of the present patent application, and should not be used for evaluating the novelty and inventive step of the present application in the case that there is no clear evidence that the above content is disclosed at the filing date of the present patent application.
Disclosure of Invention
The invention aims to provide a high performance liquid chromatography-mass spectrometry detection method for nafil pharmaceutical intermediates, so as to solve the technical problem that no related detection method for pharmaceutical intermediates tetrahydrocarboline hydrochloride exists in China at present.
For this purpose, the invention proposes the following solutions:
a high performance liquid chromatography-mass spectrometry detection method of nafil pharmaceutical intermediates comprises the following steps:
s1: grinding, crushing and uniformly mixing a solid sample, precisely weighing 1g to 0.001g, and preparing a solid sample for later use;
s2: taking a proper amount of contents of the soft capsule sample, uniformly mixing, precisely weighing 1g to 0.001g, and preparing an oil-containing sample for later use;
s3: preparing a blank sample: respectively processing the samples according to the same method as the steps S1 and S2 without adding the samples to prepare two blank solutions;
s4: accurately weighing 10mg of tetrahydrocarboline hydrochloride standard substance to prepare a standard stock solution; accurately sucking 0.1mL of standard stock solution to prepare standard intermediate solution; sucking the standard intermediate solution with the concentration of 1 mug/mL into a 10mL volumetric flask, fixing the volume to the scale with methanol, shaking up to be used as a series of standard curve solutions;
s5: performing high performance liquid chromatography-tandem mass spectrometry detection, wherein the used instruments are as follows: a high performance liquid chromatography-tandem mass spectrometer and an electrospray ion source;
s6: and identifying the medicine intermediate tetrahydrocarboline hydrochloride by the extracted ion flow diagram of the standard substance characteristic ions obtained in the step S5.
Preferably, in step S1, the step of preparing a solid sample is: grinding and crushing a solid sample, uniformly mixing, precisely weighing 1g of sample to be accurate to 0.001g, accurately adding 40mL of methanol into a 50mL volumetric flask, ultrasonically extracting for 15min, placing to room temperature, and fixing the volume to the scale by using methanol; transferring to a 100mL centrifuge tube, centrifuging at 5000r/min for 5min, filtering the supernatant with a 0.22 μm organic phase type filter membrane, and diluting with 50% methanol water solution to a linear range according to the actual concentration.
Preferably, in step S2, the step of preparing the grease sample includes: taking a proper amount of contents of a soft capsule sample, uniformly mixing, precisely weighing 1g to be accurate to 0.001g, placing the mixture in a 50mL volumetric flask, adding 5mL of ethyl acetate, shaking to disperse the mixture, adding 40mL of methanol, carrying out ultrasonic extraction for 15min, cooling to room temperature, fixing the volume to a scale with the methanol, transferring the scale to a 100mL centrifugal tube, centrifuging for 5min at 5000r/min, filtering with a 0.22 mu m organic phase type filter membrane, and properly diluting with 50% methanol water solution to a linear range according to actual concentration.
Preferably, the step S4 of preparing the standard stock solution comprises the steps of: accurately weighing 10mg of a tetrahydrocarboline hydrochloride standard substance, dissolving and diluting the tetrahydrocarboline hydrochloride standard substance to 20mL by using methanol, and shaking up to prepare a standard stock solution with the concentration of 500 mu g/mL;
preferably, the step S4 of preparing the standard intermediate solution comprises the steps of: accurately sucking 0.1mL of standard stock solution, diluting to 50mL with methanol, shaking up, and preparing into 1 μ g/mL of standard intermediate solution.
Preferably, the step S4 of preparing a series of standard curve solutions comprises: sucking standard intermediate solution with concentration of 1 mug/mL, 0.010mL, 0.020mL, 0.050mL, 0.100mL, 0.200mL, 0.500mL and 1.00mL into a 10mL volumetric flask, fixing the volume to the scale with methanol, shaking up to obtain a series of standard curve solutions with concentration of 2ng/mL, 5ng/mL, 10ng/mL, 20ng/mL, 50ng/mL and 100ng/mL, and preparing standard working solution with proper concentration according to the response condition of the instrument or the solution for fresh use.
Preferably, in the step S5 hplc-tandem mass spectrometry detection, the liquid chromatography conditions are as follows: a chromatographic column: agilent Eclipse Plus C18, 2.1mm × 100mm, 1.8 μm; mobile phase: the phase A is 0.1% formic acid water solution, and the phase B is 0.1% formic acid acetonitrile solution; flow rate: gradient elution at 400 μ L/min; column temperature: 40 ℃; sample introduction amount: 5 μ L.
Preferably, the gradient elution mode is as follows: the change of the volume percentage of the phase A is 95% → 90% at 0-1 min; the change of the volume percentage of the phase A is 90% → 50% in 1-3.5 min; at 3.5-6 min, the change of the volume percentage of the phase A is 50% → 10%; the change of the volume percentage of the phase A is 10% → 95% at 6-9 min.
Preferably, in the step S5 hplc-tandem mass spectrometry detection, the mass spectrometry conditions are as follows: continuously and directly injecting sample by a needle pump with 1 mu g/mL of standard intermediate solution, and performing ion source: an electrospray ion source; the detection mode is as follows: monitoring multiple reactions; (ii) a The scanning mode is as follows: scanning in a positive ion mode; atomizing: n is a radical of2Collision gas: and optimizing the mass spectrum parameters under the He condition.
Preferably, the optimization conditions are: capillary voltage: 3.0 kV; source temperature: 150 ℃; desolventizing temperature: 500 ℃; desolventizing agent gas flow: 1000L/Hr; taper hole gas flow: 150L/Hr; collision gas flow rate: 0.15 mL/Min.
Compared with the prior art, the invention has the advantages that:
1. at present, no related detection method of the traditional Chinese medicine intermediate tetrahydrocarboline hydrochloride exists in China, and the invention fills the gap of the analysis and detection method of the compound in China.
2. The method for determining the tetrahydrocarboline hydrochloride in the food by the ultra-high performance liquid chromatography tandem mass spectrometry has the ultra-high separation capability of the ultra-high performance liquid chromatography, and the specificity and high resolution of the mass spectrometry, and can quickly and accurately perform qualitative and quantitative analysis on a target compound. The detection result is accurate and reliable, thereby providing more reliable confirmation basis for the supervision of illegally adding chemical drugs in food and health-care food.
Drawings
FIG. 1 is an ion flow diagram of the extraction of characteristic ions of cis- (1R,3R) -1,2,3, 4-tetrahydro-1- (3, 4-methylenedioxyphenyl) -9H-pyrido [3,4-B ] indole-3-carboxylic acid methyl ester hydrochloride (i.e., tetrahydrocarboline hydrochloride) standard substance in the present invention.
Detailed Description
The present invention will be described in further detail with reference to the following detailed description and accompanying drawings. It should be emphasized that the following description is merely exemplary in nature and is not intended to limit the scope of the invention or its application.
Non-limiting and non-exclusive embodiments will be described with reference to the following figures, wherein like reference numerals refer to like parts, unless otherwise specified.
Example 1
A high performance liquid chromatography-mass spectrometry detection method of nafil pharmaceutical intermediates comprises the following steps:
(1) solid state sample preparation
Grinding and crushing a proper amount of solid sample, uniformly mixing, precisely weighing 1g of sample (accurate to 0.001g) in a 50mL volumetric flask, accurately adding 40mL of methanol, ultrasonically extracting for 15min, standing to room temperature, and fixing the volume to the scale with methanol. Transferring to a 100mL centrifuge tube, centrifuging at 5000r/min for 5min, filtering the supernatant with 0.22 μm organic phase type filter membrane, and diluting with 50% methanol water solution to linear range according to actual concentration.
(2) Preparation of oil-containing test specimens
Taking a proper amount of contents of the soft capsule sample, uniformly mixing, precisely weighing 1g (precisely to 0.001g) and placing in a 50mL volumetric flask, adding 5mL of ethyl acetate, shaking to disperse the mixture, adding 40mL of methanol, carrying out ultrasonic extraction for 15min, cooling to room temperature, fixing the volume to the scale with the methanol, transferring to a 100mL centrifugal tube, centrifuging at 5000r/min for 5min, filtering with a 0.22 mu m organic phase type filter membrane, and properly diluting with 50% methanol water solution according to actual concentration to a linear range for later use.
(3) Preparing a blank sample: respectively processing the samples according to the same method as the steps (1) and (2) without adding a sample to prepare two blank solutions;
(4) standard curve solution
Accurately weighing tetrahydrocarboline hydrochloride standard substance (molecular formula: C)20H19ClN2O4CAS number 171752-68-4, purity is more than or equal to 98%), 10mg is dissolved and diluted to 20mL by methanol, and the mixture is shaken up to prepare standard stock solution with the concentration of 500 mug/mL. The standard stock solution is stored at-20 ℃ in the dark, and the effective period is 3 months.
Accurately sucking 0.1mL of standard stock solution, diluting to 50mL with methanol, shaking up, and preparing into 1 μ g/mL of standard intermediate solution. The standard intermediate solution is prepared newly.
Sucking standard intermediate solution with concentration of 1 mug/mL, 0.010mL, 0.020mL, 0.050mL, 0.100mL, 0.200mL, 0.500mL and 1.00mL into a 10mL volumetric flask, fixing the volume to the scale with methanol, shaking up to obtain a series of standard curve solutions with concentration of 2ng/mL, 5ng/mL, 10ng/mL, 20ng/mL, 50ng/mL and 100ng/mL, and preparing standard working solution with proper concentration according to the response condition of a new clinical or instrument.
(5) High performance liquid chromatography-tandem mass spectrometry detection
a. The instrument comprises the following steps: high performance liquid chromatography-tandem mass spectrometer (Waters acquisition UPLC H-Class _ XEVO TQD): an electrospray ion source (ESI source) was provided.
a. Conditions of liquid chromatography
A chromatographic column: agilent Eclipse Plus C18(2.1 mm. times.100 mm, 1.8 μm); mobile phase: a is 0.1% formic acid aqueous solution, B is 0.1% formic acid acetonitrile solution. Flow rate: 400 μ L/min, gradient elution is shown in Table 1. Column temperature: 40 ℃; sample introduction amount: 5 μ L.
TABLE 1 gradient wash-release pattern in liquid chromatography conditions
In order to improve the separation effect and detection sensitivity of the object to be detected, the separation effects of three chromatographic columns, namely a chromatographic column Agilent Eclipse Plus C18(2.1mm multiplied by 100mm, 1.8 mu m), a ZORBAX SB-C18 chromatographic column (2.1 multiplied by 100mm, 3.5 mu m) and an ACQUITYUPLLC HSS T3(2.1 multiplied by 100mm, 1.8 mu m) are respectively examined, and the results show that the three chromatographic columns can effectively separate the target substance, wherein the Agilent Eclipse Plus C18 has better peak shape and higher column efficiency. Because the food matrix is complex, in order to protect the chromatographic column and improve the separation efficiency, the method adopts a gradient elution mode.
b. Conditions of Mass Spectrometry
Detection was performed by continuous direct injection of 1. mu.g/mL of a standard intermediate solution using a needle pump, at an ion source: electrospray ion source (ESI source); the detection mode is as follows: multiple Reaction Monitoring (MRM); (ii) a The scanning mode is as follows: scanning in a positive ion mode; atomizing: n is a radical of2Collision gas: and (3) optimizing mass spectrum parameters under the He condition, wherein the optimization condition is as follows:
capillary voltage: 3.0 kV; source Temperature (Source Temperature): 150 ℃; desolventizing Temperature (Desolvation Temperature): 500 ℃; desolvation Gas Flow (Desolvation Gas Flow): 1000L/Hr; cone Gas Flow (Cone Gas Flow): 150L/Hr; collision Gas Flow rate (Collision Gas Flow): 0.15 mL/Min. The mass spectrum conditions of the detection method for tetrahydrocarboline hydrochloride in the food are shown in table 2.
TABLE 2 Tetrahydrocarboline hydrochloride detection Mass Spectrometry conditions
Note: is a quantitative ion pair
The method for detecting tetrahydrocarboline hydrochloride in food is characterized in that the mass spectrometry is characterized in that when a chromatographic peak (the variation range is within +/-2.5%) consistent with the retention time of the chromatographic peak of the standard solution is detected in a sample, the relative abundance of a selected qualitative ion pair in a sample chromatogram is consistent with the relative abundance of ions in the standard solution with a corresponding concentration, and the deviation does not exceed the range specified in table 3, the corresponding compound can be determined to be detected in the sample, and the detection result of the embodiment of the invention is specifically shown in fig. 1.
TABLE 3 maximum permissible deviation of relative ion abundance in qualitative confirmation
According to the detection method, the concentration of the standard working solution is taken as a horizontal coordinate, the peak area of a chromatographic peak is taken as a vertical coordinate, a standard curve is drawn, the content of the tetrahydrocarboline hydrochloride is calculated by the peak area according to an external standard method, and a blank test is free of interference.
According to the method for detecting the tetrahydrocarboline hydrochloride in the food, when the sample weighing amount is 1g and the constant volume is 50mL, the detection limit is 50 mug/kg. As the HPLC-MS/MS method has the characteristics of good specificity and high sensitivity, the method is always used as the most important judgment basis for identifying the nafil substances. The qualitative and quantitative determination of the method depends on the retention time of characteristic parent ions, daughter ions and characteristic peaks. Therefore, the method can be used for detecting the content of the tetrahydrocarboline hydrochloride in the food, and achieves the purposes of fighting against illegal addition of illegal activities and ensuring the safety of the food and health-care food of the people.
And (3) specific investigation: selecting a representative substrate: taking food such as particles, oyster protein powder and the like and soft capsule health food as blank matrixes, analyzing according to a pretreatment method and a detection method determined by the standard, simultaneously accurately adding three-level standard intermediate solution of 0.05mL0.25mL0.5mL into 3 blank matrixes respectively, and preparing low, medium and high concentration levels according to the pretreatment method determined by the standard: the labeling solutions of 2ng/mL and 5ng/mL, 10ng/mL were analyzed according to the present assay to determine whether the substances present in each matrix interfere with the components being assayed. The result shows that the method has no interference to the blank substrate and the solvent of the target substance basically, the specificity is good, the three-level recovery rate is 80-105%, the relative standard deviation RSD is 0.5-2.8%, and the accuracy and precision are good.
Claims (10)
1. A high performance liquid chromatography-mass spectrometry detection method for nafil pharmaceutical intermediates is characterized by comprising the following steps:
s1: grinding, crushing and uniformly mixing a solid sample to prepare a solid sample for later use;
s2: taking a proper amount of contents of the soft capsule sample, and uniformly mixing to prepare an oil-containing sample for later use;
s3: preparing a blank sample: respectively processing the samples according to the same method as the steps S1 and S2 without adding the samples to prepare two blank solutions;
s4: accurately weighing a tetrahydrocarboline hydrochloride standard substance to prepare a standard stock solution; accurately sucking a standard stock solution to prepare a standard intermediate solution; sucking the standard intermediate solution into a 10mL volumetric flask, fixing the volume to the scale with methanol, and shaking up to obtain a series of standard curve solutions;
s5: performing high performance liquid chromatography-tandem mass spectrometry detection, wherein the used instruments are as follows: a high performance liquid chromatography-tandem mass spectrometer and an electrospray ion source;
s6: and identifying the medicine intermediate tetrahydrocarboline hydrochloride by the extracted ion flow diagram of the standard substance characteristic ions obtained in the step S5.
2. The method for HPLC-MS detection of the nafil pharmaceutical intermediate of claim 1, wherein in step S1, the step of preparing a solid sample comprises: grinding and crushing a solid sample, uniformly mixing, precisely weighing 1g of sample to be accurate to 0.001g, accurately adding 40mL of methanol into a 50mL volumetric flask, ultrasonically extracting for 15min, placing to room temperature, and fixing the volume to the scale by using methanol; transferring to a 100mL centrifuge tube, centrifuging at 5000r/min for 5min, filtering the supernatant with a 0.22 μm organic phase type filter membrane, and diluting with 50% methanol water solution to a linear range according to the actual concentration.
3. The method for detecting the nafil pharmaceutical intermediate by high performance liquid chromatography-mass spectrometry according to claim 1, wherein in step S2, the step of preparing the oil and fat sample comprises: taking a proper amount of contents of a soft capsule sample, uniformly mixing, precisely weighing 1g to be accurate to 0.001g, placing the mixture in a 50mL volumetric flask, adding 5mL of ethyl acetate, shaking to disperse the mixture, adding 40mL of methanol, carrying out ultrasonic extraction for 15min, cooling to room temperature, fixing the volume to a scale with the methanol, transferring the scale to a 100mL centrifugal tube, centrifuging for 5min at 5000r/min, filtering with a 0.22 mu m organic phase type filter membrane, and properly diluting with 50% methanol water solution to a linear range according to actual concentration.
4. The method for HPLC-MS detection of the nafil pharmaceutical intermediate of claim 1, wherein the step S4 of preparing a standard stock solution comprises the steps of: the tetrahydrocarboline hydrochloride standard substance 10mg is accurately weighed, dissolved and diluted to 20mL by methanol, and shaken up to prepare the standard stock solution with the concentration of 500 mug/mL.
5. The HPLC-MS/MS detection method for the nafil pharmaceutical intermediate of claim 1 or 4, wherein the step S4 is a step of preparing a standard intermediate solution comprising: accurately sucking 0.1mL of standard stock solution, diluting to 50mL with methanol, shaking up, and preparing into 1 μ g/mL of standard intermediate solution.
6. The HPLC-MS/MS detection method for the pharmaceutical intermediate of claim 1 or 5, wherein the step S4 is a step of preparing a series of standard curve solutions: sucking standard intermediate solution with concentration of 1 mug/mL, 0.010mL, 0.020mL, 0.050mL, 0.100mL, 0.200mL, 0.500mL and 1.00mL into a 10mL volumetric flask, fixing the volume to the scale with methanol, shaking up to obtain a series of standard curve solutions with concentration of 2ng/mL, 5ng/mL, 10ng/mL, 20ng/mL, 50ng/mL and 100ng/mL, and preparing standard working solution with proper concentration according to the response condition of the instrument or the solution for fresh use.
7. The method for HPLC-MS/MS detection of the nafil pharmaceutical intermediate of claim 1, wherein in the step S5 HPLC-tandem mass spectrometry detection, the liquid chromatography conditions are as follows: a chromatographic column: agilent eclipse Plus C18, 2.1mm × 100mm, 1.8 μm; mobile phase: the phase A is 0.1% formic acid water solution, and the phase B is 0.1% formic acid acetonitrile solution; flow rate: gradient elution at 400 μ L/min; column temperature: 40 ℃; sample introduction amount: 5 μ L.
8. The HPLC-MS detection method for the nafil pharmaceutical intermediate of claim 7, wherein the gradient elution is performed by: the change of the volume percentage of the phase A is 95% → 90% at 0-1 min; the change of the volume percentage of the phase A is 90% → 50% in 1-3.5 min; at 3.5-6 min, the change of the volume percentage of the phase A is 50% → 10%; the change of the volume percentage of the phase A is 10% → 95% at 6-9 min.
9. The method for HPLC-MS detection of the nafil class of pharmaceutical intermediate of claim 1, wherein in the step S5 HPLC-tandem mass spectrometry detection, the mass spectrometry conditions are as follows: continuously and directly injecting sample by a needle pump with 1 mu g/mL of standard intermediate solution, and performing ion source: an electrospray ion source; the detection mode is as follows: monitoring multiple reactions; the scanning mode is as follows: scanning in a positive ion mode; atomizing: n is a radical of2Collision gas: and optimizing the mass spectrum parameters under the He condition.
10. The method for hplc-ms detection of the nafil class of pharmaceutical intermediate of claim 9, wherein the optimization conditions are: capillary voltage: 3.0 kV; source temperature: 150 ℃; desolventizing temperature: 500 ℃; desolventizing agent gas flow: 1000L/Hr; taper hole gas flow: 150L/Hr; collision gas flow rate: 0.15 mL/Min.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115728428A (en) * | 2022-11-15 | 2023-03-03 | 山东省医药工业设计院有限公司 | Method for determining related substances of tadalafil intermediate cis-tetrahydrocarboline hydrochloride |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102971318A (en) * | 2010-07-06 | 2013-03-13 | 小野药品工业株式会社 | Tetrahydrocarboline derivative |
| CN105021735A (en) * | 2015-07-21 | 2015-11-04 | 中国科学院西北高原生物研究所 | Detection method for ss or/and rsMTCA in Nitraria tangutorum Bobr seeds or extract thereof |
| CN105541835A (en) * | 2015-12-31 | 2016-05-04 | 湖南千金湘江药业股份有限公司 | Cis-tetrahydrocarboline intermediate and synthesis method thereof, and application of cis-tetrahydrocarboline intermediate in preparing tadalafil |
| CN106810554A (en) * | 2017-01-14 | 2017-06-09 | 山东裕欣药业有限公司 | A kind of preparation method of Tadalafei compound |
| CN110437228A (en) * | 2019-07-22 | 2019-11-12 | 山东省药学科学院 | A kind of preparation method of Tadalafei and its intermediate |
-
2020
- 2020-03-31 CN CN202010245299.2A patent/CN111272918A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102971318A (en) * | 2010-07-06 | 2013-03-13 | 小野药品工业株式会社 | Tetrahydrocarboline derivative |
| CN105021735A (en) * | 2015-07-21 | 2015-11-04 | 中国科学院西北高原生物研究所 | Detection method for ss or/and rsMTCA in Nitraria tangutorum Bobr seeds or extract thereof |
| CN105541835A (en) * | 2015-12-31 | 2016-05-04 | 湖南千金湘江药业股份有限公司 | Cis-tetrahydrocarboline intermediate and synthesis method thereof, and application of cis-tetrahydrocarboline intermediate in preparing tadalafil |
| CN106810554A (en) * | 2017-01-14 | 2017-06-09 | 山东裕欣药业有限公司 | A kind of preparation method of Tadalafei compound |
| CN110437228A (en) * | 2019-07-22 | 2019-11-12 | 山东省药学科学院 | A kind of preparation method of Tadalafei and its intermediate |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115728428A (en) * | 2022-11-15 | 2023-03-03 | 山东省医药工业设计院有限公司 | Method for determining related substances of tadalafil intermediate cis-tetrahydrocarboline hydrochloride |
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