CN109668987A - A kind of 3- amino piperidine dihydrochloride enantiomter measurement analysis method - Google Patents
A kind of 3- amino piperidine dihydrochloride enantiomter measurement analysis method Download PDFInfo
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- amino piperidine
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- G—PHYSICS
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract
The invention discloses the measurement analysis methods of 3- amino piperidine dihydrochloride enantiomter content, this method passes through the free 3- amino piperidine dihydrochloride of inorganic base in aqueous organic solvent, derived with arene acyl chlorides, extraction, then the content that isomers in derivative is measured with high performance liquid chromatography, to obtain the content of isomers in 3- amino piperidine dihydrochloride.The features such as analysis method has easy to operate, favorable reproducibility, and specificity is good, high sensitivity, is easy to normalizing operation.
Description
Technical field
The present invention relates to 3- amino piperidine dihydrochloride is derived with arene acyl chlorides, is surveyed and derived with high performance liquid chromatography
The content of enantiomter in object, to calculate enantiomter content in 3- amino piperidine dihydrochloride.The method can be compared with
(S) -3- amino piperidine dihydrochloride in good control amber love song Ge Lieting starting material (R) -3- amino piperidine dihydrochloride
Content provides safeguard for the healthy medication of patient, belongs to pharmaceutical technology field.
Technical background
(R) -3- amino piperidine dihydrochloride is the important starting material in amber love song Ge Lieting synthesis process, is being synthesized
It is also easy to produce enantiomter in the process, such as cannot effectively control the quality of (R) -3- amino piperidine dihydrochloride, it will be to amber
The quality of love song Ge Lieting bulk pharmaceutical chemicals brings strong influence.Therefore establish and measure pair of (R) -3- amino piperidine dihydrochloride
Isomers measuring method is reflected to have great importance.(R) -3- amino piperidine dihydrochloride structure is as follows:
Great the choosing property of enantiomter content in measurement (R) -3- amino piperidine dihydrochloride of accurate quantitative analysis.3- ammonia
Phenylpiperidines dihydrochloride polarity is very big, without sensitive UV absorption functional group.Therefore it is difficult with using gas phase, liquid chromatogram
Its enantiomter is directly measured with other analysis means.
Currently, it is to be rarely reported that the method for the enantiomter content in measurement 3- amino piperidine dihydrochloride, which uses,.But
There are relevant report, Watanabe et al. (TetsuyaAssignee about 3- amino piperidine enantiomerism body detecting method
Sumitomo Chemical Co., Ltd., Japan 2009) use propyl chlorocarbonate for derivative reagent to 3- amino piperidine into
Row derives, and carries out analysis detection with CHIRALCEL AS-RH (50 × 4.6mm) chiral column；Sun Fengxia etc. uses (R)-Alpha-Methyl-
2- naphthalene chloroacetic chloride, chlorobenzoyl chloride, (R)-(+) -1- phenylethanesulfonyl chloride difference derivating agent derive 3- amino piperidine, use hand
Property chromatographic column analyzes it detection.Since 3- amino piperidine dihydrochloride is the hydrochloride of 3- amino piperidine, can not pass through
The method of above-mentioned report carries out the analysis detection of enantiomter.3- amido piperidine hydrochlorate manufacturing enterprise is generally by having
Triethylamine is added in solvent come the 3- amino piperidine dihydrochloride that dissociates, adds derivative reagent derivative, is then evaporated derivative, it is multiple
It is molten, it is finally detected with liquid chromatogram, cumbersome, repeated and precision all haves the defects that very big.
Summary of the invention
In order to overcome the drawbacks of the prior art, the present invention provides a kind of surveys of 3- amino piperidine dihydrochloride enantiomter
Setting analysis method.
Using in aqueous organic solvent, addition inorganic base is come the 3- amino piperidine dihydrochloride that dissociates, with arene acyl
Chlorine reacts to form stable derivative with 3- amino piperidine, and extraction is measured with liquid chromatograph.This method has operation letter
Just, reproducible, the advantages that precision is high, and specificity is good.
A kind of 3- amino piperidine dihydrochloride enantiomter measurement analysis method, includes the following steps:
Step 1: 3- amino piperidine dihydrochloride is dissolved in aqueous organic solution, act on forming 3- by inorganic base
Amino piperidine；
Step 2: the derivative reagent of acyl chlorides containing arene and 3- amino piperidine form derivative；
Step 3: extraction derivative, with the content of enantiomter in high effective liquid chromatography for measuring derivative, thus
Out in 3- amino piperidine dihydrochloride enantiomter content.
Preferably, organic solution aqueous in step 1 is the mixture of water and organic solvent, organic solvent are as follows: methanol,
Ethyl alcohol or acetonitrile, the content volume for accounting for organic solution of organic solvent is than 0~80%.
Preferably, the content volume ratio of organic solvent is 50%.
Preferably, inorganic base is sodium carbonate, potassium carbonate, sodium bicarbonate, saleratus, preferably potassium carbonate or carbon in step 1
Sour sodium.
Preferably, arene acyl chlorides be chlorobenzoyl chloride, to methyl benzoyl chloride, face methyl benzoyl chloride, methylbenzene
Formyl chloride, 3,5- dimethoxy-4 '-methyl benzoyl chloride, 4- trifluoromethyl benzoyl chloride, 3- trifluoromethyl benzoyl chloride, 3- first
Base -4- methoxy benzoyl chloride.
Preferably, arene acyl chlorides is chlorobenzoyl chloride.
Preferably, arene acyl chlorides and (R) -3- amino piperidine dihydrochloride molar ratio are 15:1~60:1.
Preferably, inorganic base and (R) -3- amino piperidine dihydrochloride molar ratio are 3:1~13:1.
Preferably, extractant selects n-hexane or normal heptane；Solvent quantity and sample solution volume are 1:10~5:10.
Preferably, the detection method includes the preparation of the preparation of test solution, reference substance solution, and system suitability is molten
The preparation of liquid and its several step of measurement:
(1) preparation of system suitability solution: amber love song Ge Lieting raw material (R) -3- amino piperidine dihydrochloride pair is taken
According to product and (S) -3- amino piperidine dihydrochloride reference substance, inorganic base is added, dissolves constant volume with dilution, every 1ml is made and contains
(R) -3- amino piperidine dihydrochloride ((S) -3- amino piperidine dihydrochloride that at least every 1ml contains 12.5ug) of 2.5mg, adds
Enter derivative reagent is added, sufficiently after reaction, extraction takes supernatant as system suitability solution.
(2) preparation of test solution: taking amber love song Ge Lieting raw material (R) -3- amino piperidine dihydrochloride reference substance,
Inorganic base is added, dissolves constant volume with dilution, (R) -3- amino piperidine dihydrochloride of every 1ml containing 2.5mg is made, be added and derive
Reagent, sufficiently after reaction, extraction takes supernatant as test solution.
(3) determination step: precision measures system suitability solution 40ul and injects liquid chromatograph, and it is sensitive to adjust detector
Degree makes the 10%~20% of the peak height full scale of principal component chromatographic peak, then the accurate test solution 40ul that measures injects liquid phase
Chromatograph records chromatogram.
Dilution are as follows: 50% ethanol water.
The purpose of the present invention is to provide a kind of using derivating agent and HPLC method to 3- amino piperidine dihydrochloride mapping
The method of isomers progress quantitative analysis detection.Using containing 2 amino this features in 3- amino piperidine dihydrochloride molecule,
Its characteristic can be transformed to be allowed to convert the molecular structure of suitable chromatogram quantitative analysis of the liquid phase.It can be with arene acyl using amino
This feature of chlorine fast quantification reaction.In addition to this, which has preferable UV absorption in UV detector, excessive
Arene acyl chlorides reacted with inorganic base (sodium carbonate or potassium carbonate) generate salt, derivative is extracted by extractant,
It is suitble to normal-phase chromatography analysis.
Concrete operations are as follows:
Step 1: free
3- amino piperidine dihydrochloride is dissolved in aqueous organic solvent, be added suitable inorganic base (sodium carbonate or
Potassium carbonate) so that the 3- amino piperidine dihydrochloride is dissociated into 3- amino piperidine.Reaction equation is shown in formula 1
Step 2, derivatization
Free 3- amino piperidine out is performed the derivatization with arene acyl chlorides under normal temperature conditions, adjusts 3- amino piperidine
With arene acyl chlorides into molar ratio, carry out derivatization reaction, reaction equation is shown in formula 2
Step 3, extraction
Derivative products have been extracted into several layers of from water layer with extractant (n-hexane or normal heptane), have been carried out by HPLC
Detection.
Being found by experiment that 3- amino piperidine in aqueous solution has extraordinary dissolubility, and the present invention will use 50% ethyl alcohol
Aqueous solution is as dilution.The key point of the analysis method is that suitable water is 1. added in dilution, makes 3- amino piperidine two
Hydrochloride has preferable dissolubility；2. suitable inorganic base is added in dilution, enable 3- amino piperidine dihydrochloride
Good separate out obtains 3- amino piperidine, and inorganic base can also consume excessive chlorobenzoyl chloride, and in extraction process
Faster layering；3. arene acyl chlorides provides good UV absorption functional group for derivative products, convenient for being waken up with a start with HPLC-UV
Analysis；4. 3- amino piperidine derivatives are extracted from saying in solution by extractant, and the derivating agent and nothing that unreacted is complete
Machine alkali forms salt, stays in water phase, so that component is relatively single in extract liquor, is convenient for chromatography.
Starting material (R) -3- amino piperidine dihydrochloride mapping is different in amber love song Ge Lieting bulk pharmaceutical chemicals
Structure body measures analysis method, and this method acts on forming 3- amino piperidine by inorganic base and 3- amino piperidine dihydrochloride, with virtue
Fragrant hydro carbons acyl chlorides forms derivative as derivative reagent and 3- amino piperidine, and 3- amino piperidine derivatives are extracted with extractant,
With the content of enantiomter in high effective liquid chromatography for measuring (R) -3- amino piperidine derivatives, to obtain (R) -3- amino
The content of enantiomter in piperidines dihydrochloride.
Organic solvent is the combination of one or more of methanol, ethyl alcohol and acetonitrile in above-mentioned aqueous organic solvent,
Ratio 20%:80%~100%:0% of water and organic phase, preferably 50% ethanol solution.
Above-mentioned inorganic base is sodium carbonate, potassium carbonate, sodium bicarbonate and saleratus, preferably sodium carbonate and potassium carbonate；Carbonic acid
Sodium and potassium carbonate and (R) -3- amino piperidine dihydrochloride molar ratio are 3:1~13:1.
Above-mentioned arene acyl chlorides be chlorobenzoyl chloride, to methyl benzoyl chloride, face methyl benzoyl chloride, toluyl
Chlorine, 3,5- dimethoxy-4 '-methyl benzoyl chloride, 4- trifluoromethyl benzoyl chloride, 3- trifluoromethyl benzoyl chloride, 3- methyl-
4- methoxy benzoyl chloride, preferably chlorobenzoyl chloride；Chlorobenzoyl chloride and (R) -3- amino piperidine dihydrochloride molar ratio be 15:1~
60:1。
It is above-mentioned using 3- amino piperidine derivatives by n-hexane or normal heptane as extractant；Solvent quantity and sample
Product liquor capacity is 1:10~5:10.
The technical solution adopted by the invention is as follows:
Sample pre-treatments:
Dilution: 50% ethanol water.
Inorganic base: sodium carbonate or potassium carbonate
Derivating agent: chlorobenzoyl chloride
Extractant: n-hexane or normal heptane
System suitability solution: amber love song Ge Lieting raw material (R) -3- amino piperidine dihydrochloride reference substance and (S)-are taken
The inorganic base of 10 times of 3- amino piperidine dihydrochloride moles is added in 3- amino piperidine dihydrochloride reference substance, molten with dilution
Constant volume is solved, (R) -3- amino piperidine dihydrochloride ((the S) -3- ammonia that at least every 1ml contains 12.5ug of every 1ml containing 2.5mg is made
Phenylpiperidines dihydrochloride), chlorobenzoyl chloride is added, under room temperature, after reacting 30min, extraction takes supernatant molten as system suitability
Liquid.
The preparation of test solution: amber love song Ge Lieting raw material (R) -3- amino piperidine dihydrochloride reference substance is taken, is added
Enter the inorganic base of 10 times of 3- amino piperidine dihydrochloride moles is added, dissolve constant volume with dilution, every 1ml is made containing 2.5mg
(R) -3- amino piperidine dihydrochloride, chlorobenzoyl chloride is added, under room temperature, after reacting 30min, with extractant (n-hexane or just
Heptane) extraction, take supernatant as test solution.
Measurement: precision measures system suitability solution 40ul and injects liquid chromatograph, adjusts detector sensitivity, precision amount
It takes test solution 40ul to inject liquid chromatograph, records chromatogram.
The chromatographic column that the present invention uses is the chromatographic column of amylose-three (3,5- dimethylphenylcarbamate), stream
0.5~1.0ml/min of speed.30 DEG C~40 DEG C of column temperature.Mobile phase A: n-hexane, Mobile phase B: ethyl alcohol, UV detector wavelength:
254nm
Gradient is as follows:
| Time | A/% | B/% |
| 0min | 80 | 20 |
| 15min | 80 | 20 |
。
The invention discloses the measurement analysis method of 3- amino piperidine dihydrochloride enantiomter content, this method is containing
By the free 3- amino piperidine dihydrochloride of inorganic base in the organic solvent of water, is derived with arene acyl chlorides, extracted, so
The content for measuring isomers in derivative with high performance liquid chromatography afterwards, to obtain isomers in 3- amino piperidine dihydrochloride
Content.The features such as analysis method has easy to operate, favorable reproducibility, and specificity is good, high sensitivity, is easy to normalizing operation.
Detailed description of the invention
Attached drawing 1: the according to embodiments of the present invention 1 obtained liquid-derived map of dilution；
Attached drawing 2: the according to embodiments of the present invention 1 obtained derivative map of system suitability solution；
Attached drawing 3: according to embodiments of the present invention 1 obtained (S) -3- amino piperidine dihydrochloride reference substance derivative map；
Attached drawing 4: according to embodiments of the present invention 2 obtained (R) -3- amino piperidine dihydrochloride test sample derivative maps.
Attached drawing 5: according to embodiments of the present invention 3 obtained (R) -3- amino piperidine dihydrochloride test samples add (S) -3- amino
Piperidines dihydrochloride rate of recovery map.
Attached drawing 6: according to embodiments of the present invention 4 obtained (R) -3- amino piperidine dihydrochloride test samples add (S) -3- amino
Piperidines dihydrochloride rate of recovery map.
Attached drawing 7: according to embodiments of the present invention 4 obtained (S) -3- amino piperidine dihydrochloride test samples add (S) -3- amino
Piperidines dihydrochloride rate of recovery map.
Specific embodiment
For a better understanding of the technical solution of the present invention, making furtherly below with reference to specific embodiments of the present invention
It is bright, but it is not limited to the present invention.
Embodiment one
Instrument and condition:
High performance liquid chromatograph: Agilent 1100 is with UV detector.
Chromatographic column: DAICEL AD-H, 4.6mm*250mm*5um
Mobile phase: A: n-hexane B: ethyl alcohol.
Isocratic as follows: 0~15min, n-hexane ratio keep 80%.
Column temperature: 35 DEG C
Flow velocity: 1ml/min
Detection wavelength: 254nm
Sampling volume: 40ul
Implementation steps:
1) dilution: 200ml methanol is dissolved in 200ml water, is mixed, ultrasonic degassing.
2) placebo solution A: accurately weighing 100mg sodium carbonate in 20ml ml headspace bottle, and 10ml dilution is added.Ultrasound
The chlorobenzoyl chloride reaction 30min of addition 0.5ml after 10min is placed in dissolution.Addition 5ml n-hexane shakes quiet ten minutes later repeatedly
It sets, solution layering takes upper organic phase to detect.See typical spectrum Fig. 1
3) (S) -3- amino piperidine dihydrochloride reference substance stock solution B: (S) -3- amino piperidine of 12.5mg is accurately weighed
Dihydrochloride reference substance adds dilution to dissolve and is diluted to scale and shake up in 100ml measuring bottle.
4) reference substance and 25mg of (R) -3- amino piperidine dihydrochloride of 25mg system suitability solution C: are weighed
(S) in 20ml ml headspace bottle 100mg sodium carbonate is added, with 50% ethyl alcohol of 9ml in the reference substance of -3- amino piperidine dihydrochloride
Aqueous solution.Ultrasonic dissolution places the chlorobenzoyl chloride reaction 30min of addition 0.5ml after 10min.5ml n-hexane is added to shake repeatedly
It is stood after 10min, solution layering takes upper organic phase to detect.See typical spectrum Fig. 2
5) (S) -3- amino piperidine dihydrochloride reference substance solution D: precision measures the B of 1ml in 20ml ml headspace bottle, is added
100mg sodium carbonate and the 50% ethanol water ultrasonic dissolution for adding 9ml place the chlorobenzoyl chloride reaction of addition 0.5ml after 10min
30min.Addition 5ml n-hexane shakes repeatedly to be stood ten minutes later, and solution layering takes upper organic phase to detect.See typical spectrum Fig. 3
Embodiment two
Instrument and condition:
High performance liquid chromatograph: Agilent 1100 is with UV detector.
Chromatographic column: DAICEL AD-H, 4.6mm*250mm*5um
Mobile phase: A: n-hexane B: ethyl alcohol.
Isocratic as follows: 0~15min, n-hexane ratio keep 80%.
Column temperature: 35 DEG C
Flow velocity: 1ml/min
Detection wavelength: 254nm
Sampling volume: 40ul
Implementation steps:
1) dilution: 200ml methanol is dissolved in 200ml water, is mixed, ultrasonic degassing.
2) test solution E: weighing the test sample of (R) -3- amino piperidine dihydrochloride of 25mg in 20ml ml headspace bottle,
50% ethanol water of 100mg sodium carbonate and 10ml is added.Ultrasonic dissolution places the chlorobenzoyl chloride of addition 0.5ml after 10min
React 30min.Addition 5ml n-hexane shakes repeatedly to be stood ten minutes later, and solution layering takes upper organic phase to detect.See typical spectrum
Fig. 4
Embodiment three
Instrument and condition:
High performance liquid chromatograph: Agilent 1100 is with UV detector.
Chromatographic column: DAICEL AD-H, 4.6mm*250mm*5um
Mobile phase: A: n-hexane B: ethyl alcohol.
Isocratic as follows: 0~15min, n-hexane ratio keep 80%.
Column temperature: 35 DEG C
Flow velocity: 1ml/min
Detection wavelength: 254nm
Sampling volume: 40ul
Implementation steps:
1) dilution: 200ml methanol is dissolved in 200ml water, is mixed, ultrasonic degassing.
2) (S) -3- amino piperidine dihydrochloride reference substance stock solution B: (S) -3- amino piperidine of 12.5mg is accurately weighed
Dihydrochloride reference substance adds dilution to dissolve and is diluted to scale and shake up in 100ml measuring bottle.
3) (R) -3- amino piperidine dihydrochloride mark-on solution F: (R) -3- amino piperidine dihydrochloride of 25mg is weighed
In 20ml ml headspace bottle the B of 100mg sodium carbonate and 1ml is added, with 50% ethanol water of 9ml in test sample.Ultrasonic dissolution,
The chlorobenzoyl chloride that 0.5ml is added after placement 10min reacts 30min.Addition 5ml n-hexane shakes repeatedly to be stood ten minutes later, molten
Liquid layering takes upper organic phase to detect.See typical spectrum Fig. 5
Example IV
Instrument and condition:
High performance liquid chromatograph: Agilent 1100 is with UV detector.
Chromatographic column: DAICEL AD-H, 4.6mm*250mm*5um
Mobile phase: A: n-hexane B: ethyl alcohol.
Isocratic as follows: 0~15min, n-hexane ratio keep 80%.
Column temperature: 35 DEG C
Flow velocity: 1ml/min
Detection wavelength: 254nm
Sampling volume: 40ul
Implementation steps:
1) dilution: 200ml methanol is dissolved in 200ml water, is mixed, ultrasonic degassing.
2) (S) -3- amino piperidine dihydrochloride reference substance stock solution B: (S) -3- amino piperidine of 12.5mg is accurately weighed
Dihydrochloride reference substance adds dilution to dissolve and is diluted to scale and shake up in 100ml measuring bottle.
3) system suitability solution G: the reference substance of (R) -3- amino piperidine dihydrochloride of 25mg is weighed in 20ml head space
In bottle, the B of 200mg sodium carbonate and 1ml is added, with 50% ethanol water of 9ml.Ultrasonic dissolution is added after placing 10min
The chlorobenzoyl chloride of 1.0ml reacts 30min.Addition 5ml n-hexane shakes repeatedly to be stood ten minutes later, and solution layering takes upper layer organic
Mutually detect.See typical spectrum Fig. 6
4) system suitability Solution H: the reference substance of (R) -3- amino piperidine dihydrochloride of 25mg is weighed in 20ml head space
In bottle, the B of 50mg sodium carbonate and 1ml is added, with 50% ethanol water of 9ml.Ultrasonic dissolution is added after placing 10min
The chlorobenzoyl chloride of 0.25ml reacts 30min.Addition 5ml n-hexane shakes repeatedly to be stood ten minutes later, and solution layering takes upper layer to have
Machine mutually detects.See typical spectrum Fig. 7.
Claims (10)
1. a kind of 3- amino piperidine dihydrochloride enantiomter measures analysis method, characterized by the following steps:
Step 1: 3- amino piperidine dihydrochloride is dissolved in aqueous organic solution, act on forming 3- amino by inorganic base
Piperidines；
Step 2: the derivative reagent of acyl chlorides containing arene and 3- amino piperidine form derivative；
Step 3: extraction derivative, with the content of enantiomter in high effective liquid chromatography for measuring derivative, to obtain 3-
The content of enantiomter in amino piperidine dihydrochloride.
2. according to the method described in claim 1, it is characterized by: organic solution aqueous in step 1 is water and organic solvent
Mixture, organic solvent are as follows: methanol, ethyl alcohol or acetonitrile, the content volume for accounting for organic solution of organic solvent is than 0~80%.
3. according to the method described in claim 2, it is characterized by: the content volume ratio of organic solvent is 50%.
4. according to the method described in claim 1, it is characterized by: inorganic base is sodium carbonate, potassium carbonate, bicarbonate in step 1
Sodium, saleratus.
5. method according to claim 1, it is characterised in that: arene acyl chlorides is chlorobenzoyl chloride, to methyl in step 2
Chlorobenzoyl chloride faces methyl benzoyl chloride, m-methyl benzoyl formyl chloride, 3,5- dimethoxy-4 '-methyl benzoyl chloride, 4- trifluoromethyl
Chlorobenzoyl chloride, 3- trifluoromethyl benzoyl chloride, 3- methyl -4- methoxy benzoyl chloride.
6. according to claim 5, it is characterised in that: arene acyl chlorides and (R) -3- amino piperidine dihydrochloride molar ratio
For 15:1~60:1.
7. method according to claim 1, it is characterised in that: inorganic base is potassium carbonate or sodium carbonate in step 1；Step 2
Middle arene acyl chlorides is chlorobenzoyl chloride.
8. according to the method described in claim 1, it is characterized by: inorganic base and (R) -3- amino piperidine dihydrochloride molar ratio
For 3:1~13:1；Extractant selects n-hexane or normal heptane；Solvent quantity and sample solution volume are 1:10~5:10.
9. according to the method described in claim 1, it is characterized by: the step 3 detection method includes the system of test solution
Standby, reference substance solution preparation, the preparation of system suitability solution and its several step of measurement, the specific steps are as follows:
(1) preparation of system suitability solution: amber love song Ge Lieting raw material (R) -3- amino piperidine dihydrochloride reference substance is taken
Inorganic base is added in (S) -3- amino piperidine dihydrochloride reference substance, dissolves constant volume with dilution, every 1ml is made and contains
Derivative reagent is added in (R) -3- amino piperidine dihydrochloride of 12.5ug-2.5mg, and sufficiently after reaction, extraction takes supernatant to make
For system suitability solution；
(2) preparation of test solution: taking amber love song Ge Lieting raw material (R) -3- amino piperidine dihydrochloride reference substance, is added
Inorganic base dissolves constant volume with dilution, (R) -3- amino piperidine dihydrochloride that every 1ml contains 12.5ug-2.5mg is made, adds
Enter derivative reagent, sufficiently after reaction, extraction takes supernatant as test solution；
(3) determination step: precision measures system suitability solution 40ul and injects liquid chromatograph, adjusts detector sensitivity, makes
The peak height of principal component chromatographic peak is the 10%~20% of full scale, then the accurate test solution 40ul that measures injects liquid chromatogram
Instrument records chromatogram.
10. according to the method described in claim 9, it is characterized by: dilution are as follows: 50% ethanol water.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116482280A (en) * | 2023-05-22 | 2023-07-25 | 北京北陆益康医药研发有限公司 | Method for determining aminopiperidine dihydrochloride isomer |
| CN116660417A (en) * | 2023-06-02 | 2023-08-29 | 北京北陆益康医药研发有限公司 | Determination method and application of R-3-aminopiperidine dihydrochloride in bulk drug |
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