CN108241030A - The assay method of compound I content in a kind of BUPROPIONE HCl - Google Patents
The assay method of compound I content in a kind of BUPROPIONE HCl Download PDFInfo
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- CN108241030A CN108241030A CN201611225836.7A CN201611225836A CN108241030A CN 108241030 A CN108241030 A CN 108241030A CN 201611225836 A CN201611225836 A CN 201611225836A CN 108241030 A CN108241030 A CN 108241030A
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- Prior art keywords
- compound
- acetonitrile
- bupropione hcl
- solution
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
Abstract
The invention discloses 2 bromine, 3 ' chlorophenyl acetone in a kind of BUPROPIONE HCl (hereinafter referred to as：Compound I) content assay method, this method is using chemically derived and combine the content that high performance liquid chromatography mass spectrometer measures compound I in BUPROPIONE HCl.The analysis method is good with specificity compared with prior art, and favorable reproducibility, sensitivity is high, the features such as being suitble to do trace analysis.
Description
Technical field
The present invention relates to use chemically derived and determine BUPROPIONE HCl with reference to High Performance Liquid Chromatography-Mass Spectrometry instrument
The middle bromo- 3 '-chlorophenyl acetones of 2- are (hereinafter referred to as：Compound I) content.The method can preferably control trace in bulk pharmaceutical chemicals and preparation
The content of compound I is measured, the healthy and safe medication for patient provides safeguard, and belongs to pharmaceutical technology field.
Technical background
BUPROPIONE HCl, chemical name 2- (tert-butylamino) -1- (3-chlorophenyl) propan-1-
one。
BUPROPIONE HCl is auxiliary smoking deterent and antidepressants.Its main mechanism is to inhibit taking the photograph again for DA and NE
It takes, so as to play antidepressant effect.BUPROPIONE HCl structure is as follows：
Containing remaining compound I is reacted in BUPROPIONE HCl, structure is as follows：
The compound I content for measuring to accurate quantitative analysis trace in BUPROPIONE HCl is extremely challenging.Be difficult to adopt gas phase,
Liquid chromatogram etc. carries out trace to it and directly measures.
At present, in the BUPROPIONE HCl of only classical chromatography determination constant compound I content method, it is single-minded
Property, sensitivity, method precision and repeatability all exist it is very big the defects of, it is impossible to reliable trace analysis result is provided.In order to
The defects of overcoming original method, the present invention are non-using chemically derived and combination High Performance Liquid Chromatography-Mass Spectrometry instrument measure hydrochloric acid peace
The content of compound I in his ketone.The analysis method has the characteristics that easy to operate, specificity is good, sensitive high, favorable reproducibility.
It is as follows that it derives principle：
Invention content
As described above, directly there are various defects by compound I in accurate quantitative analysis measure trace hydrochloric acid Bupropion.However,
Be very suitable for derivatization reaction and derivative products using compound I has stable and Mass Spectrometer Method in reversed-phase liquid chromatography
The characteristics of molecular structure of the suitable quantitative analysis of ionization is easy in device, may be used High Performance Liquid Chromatography-Mass Spectrometry
Instrument directly measures.In addition to this, compound I derivative products have in mass detector and sensitively absorb this feature and make this method
Sensitivity and specificity greatly improve.
It is found by experiment that BUPROPIONE HCl in acetonitrile：Water=50：There is extraordinary dissolubility in 50 (%V/V), because
This present invention will use acetonitrile：Water=50：50 (%V/V) are as diluent.
The present invention relates to a kind of assay method of compound I content in BUPROPIONE HCl, this method for it is chemically derived simultaneously
The content of compound I in BUPROPIONE HCl is measured with reference to High Performance Liquid Chromatography-Mass Spectrometry instrument.
Acetonitrile is used in above-mentioned sample preparation：Water=50：50 (%V/V) are as dilution.
It is above-mentioned to use High Performance Liquid Chromatography-Mass Spectrometry instrument, cation choice ion pattern.
This method includes following steps：
(1) BUPROPIONE HCl raw material or powder formulation are taken, with acetonitrile：Water=50：50 (%V/V) solution are as dilution
Sample solution is prepared；
(2) using octadecyl silane chromatographic column, mobile phase is 0.05%-0.2% formic acid or acetic acid or trifluoro second
Aqueous acid and acetonitrile carry out gradient elution.
(3) setting flow rate of mobile phase is 0.3-1.2mL/min, and column temperature is controlled between 25 DEG C -40 DEG C.
(4) the 10 μ L of sample solution of step (1) are taken, sample introduction records mass spectrum total ion current figure.
(5) using mass detector, ion mode selection cation takes the sample solution sample introduction of (1), records compound I
Derivative mass spectral ion current figure.
(6) using 2- mercaptopyridines acetonitrile solution as derivative liquid.
The technical solution adopted by the present invention is as follows：
Sample pre-treatments：
Dilution：Acetonitrile：Water=50：50 (%V/V).
Compound I derivative standard solution：The Compound I solution of 33ng/mL is prepared with dilution precision.It takes isometric
The solution and derivative liquid mixing are carried out after deriving, sample introduction.
Sample solution：Precision weighs 100mg samples in the volumetric flask of 10mL, is dissolved with dilution and is settled to scale,
Isometric solution and derivative liquid mixing is taken to carry out after deriving, sample introduction.
The present invention is using chromatographic column：Octadecyl silane chromatographic column.Flow velocity 0.3-1.2mL/min.25 DEG C of column temperature-
40℃.Mobile phase A：0.05%-0.2% formic acid or acetic acid or trifluoroacetic acid aqueous solution, Mobile phase B：Acetonitrile, gradient are as follows：
| A | B | |
| 0min | 90% | 10% |
| 8min | 10% | 90% |
Mass detector：Positive ion mode, [M+H]+：278
Description of the drawings：
Attached drawing 1：According to embodiments of the present invention 1 obtained compound I derivative mass spectrum rod figures；
Attached drawing 2：According to embodiments of the present invention 1 obtained compound I standard items derivative mass spectrum total ion current figures；
Attached drawing 3：According to embodiments of the present invention 2 obtained BUPROPIONE HCl sample mass spectrum total ion current figures；
Attached drawing 4：According to embodiments of the present invention 3 obtained BUPROPIONE HCl sample pipetting volume rate of recovery mass spectrum total ion currents
Figure.
Specific embodiment
For a better understanding of the technical solution of the present invention, make furtherly 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 chromatography mass spectrometer：Agilent 1260infinity, MS detectors.
Chromatographic column：Octadecyl silane chromatographic column
Mobile phase：A：0.05%-0.2% formic acid or acetic acid or trifluoroacetic acid aqueous solution B：Acetonitrile.
Gradient is as follows：0~8.0min, organic Phase Proportion become 90% from 10%.
Column temperature：35℃.
Flow velocity：1.0mL/min
Select cation：278
Sampling volume：5μL
Experimental procedure：
1) mobile phase A is prepared：Precision measures 1.0mL trifluoroacetic acids and is dissolved in 1000mL water, mixing.
2) dilution B：Acetonitrile：Water=50：50 (%V/V)
3) standard solution C：Precision weighs about 33mg compounds I in 100mL volumetric flasks, and B is added to dissolve constant volume, is shaken up, essence
Close measurement 2.0mL is placed in another 100mL volumetric flasks, is added B constant volumes, is shaken up, and precision measures 1.0mL and is placed in another 100mL capacity
In bottle, add B constant volumes, isometric solution and derivative liquid mixing is taken to carry out recording matter after deriving to get standard solution C, sample introduction
Rod figure is composed, sees attached drawing 1.Compound I derivative mass spectrum total ion current figures are recorded, see attached drawing 2.
Embodiment two
Instrument and condition：
High performance liquid chromatograph：Agilent 1260infinity, MS detectors.
Chromatographic column：Octadecyl silane chromatographic column
Mobile phase：A：0.05%-0.2% formic acid or acetic acid or trifluoroacetic acid aqueous solution B：Acetonitrile.
Gradient is as follows：0~8.0min, organic Phase Proportion become 90% from 10%.
Column temperature：35℃.
Flow velocity：1.0mL/min
Select cation：278
Sampling volume：5μL
Experimental procedure：
1) mobile phase A is prepared：Precision measures 1.0mL trifluoroacetic acids and is dissolved in 1000mL water, mixing.
2) dilution B：Acetonitrile：Water=50：50 (%V/V)
3) standard solution C：Precision weighs about 33mg compounds I in 100mL volumetric flasks, and B is added to dissolve constant volume, is shaken up, essence
Close measurement 2.0mL is placed in another 100mL volumetric flasks, is added B constant volumes, is shaken up, and precision measures 1.0mL and is placed in another 100mL capacity
In bottle, add B constant volumes, isometric solution and derivative liquid mixing is taken to carry out after deriving to get standard solution C.
4) sample solution D：Precision weighs about 200mg BUPROPIONE HCl samples and is placed in 10mL volumetric flasks, adds B constant volumes,
Isometric solution and derivative liquid mixing is taken to carry out after deriving to get sample solution D, sample introduction.Record compound I derived materials
Total ion current figure is composed, sees attached drawing 3.
Embodiment three
Instrument and condition：
High performance liquid chromatograph：Agilent 1260infinity, MS detectors.
Chromatographic column：Octadecyl silane chromatographic column
Mobile phase：A：0.05%-0.2% formic acid or acetic acid or trifluoroacetic acid aqueous solution B：Acetonitrile.
Gradient is as follows：0~8.0min, organic Phase Proportion become 90% from 10%.
Column temperature：35℃.
Flow velocity：1.0mL/min
Select cation：278
Sampling volume：5μL
Experimental procedure：
1) mobile phase A is prepared：Precision measures 1.0mL trifluoroacetic acids and is dissolved in 1000mL water, mixing.
2) dilution B：Acetonitrile：Water=50：50 (%V/V)
3) standard solution C：Precision weighs about 33mg compounds I in 100mL volumetric flasks, and B is added to dissolve constant volume, is shaken up, essence
Close measurement 2.0mL is placed in another 100mL volumetric flasks, is added B constant volumes, is shaken up, and precision measures 1.0mL and is placed in another 100mL capacity
In bottle, add B constant volumes, isometric solution and derivative liquid mixing is taken to carry out after deriving to get standard solution C.
4) sample solution D：Precision weighs about 200.0mg BUPROPIONE HCl samples, is dissolved and is titrated to standard solution C
Scale, mixing take isometric solution and derivative liquid mixing to carry out after deriving, sample introduction.It is total to record compound I derivative mass spectrums
Ion flow graph is shown in attached drawing 4.
Claims (3)
1. the bromo- 3 '-chlorophenyl acetones of doubtful genotoxicity impurity 2- are (hereinafter referred to as in a kind of BUPROPIONE HCl：Compound I) contain
The assay method of amount, it is characterised in that it is non-that hydrochloric acid peace is measured using chemically derived and combination High Performance Liquid Chromatography-Mass Spectrometry instrument
The content of the compound I of trace in his ketone.
2. analysis method according to claim 1, it is characterised in that use is chemically derived and combines high performance liquid chromatography-matter
Compose combined instrument, ion mode selection cation.
3. according to claim 1, it is characterised in that this method includes following steps：
(1) BUPROPIONE HCl raw material or powder formulation are taken, with acetonitrile：Water=50：50 (%V/V) are prepared as dilution
Sample solution；
(2) using octadecyl silane chromatographic column, mobile phase is 0.05%-0.2% formic acid or acetic acid or trifluoroacetic acid water
Solution and acetonitrile carry out gradient elution.
(3) setting flow rate of mobile phase is 0.3-1.2mL/min, and column temperature is controlled between 25 DEG C -40 DEG C.
(4) the 5 μ L of sample solution of step (1) are taken, sample introduction records mass spectrum total ion current figure.
(5) using mass detector, ion mode selection cation takes the sample solution sample introduction of (1), records mass spectral ion current
Figure.
(6) using 2- mercaptopyridine acetonitrile solutions as derivatization reagent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611225836.7A CN108241030A (en) | 2016-12-27 | 2016-12-27 | The assay method of compound I content in a kind of BUPROPIONE HCl |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611225836.7A CN108241030A (en) | 2016-12-27 | 2016-12-27 | The assay method of compound I content in a kind of BUPROPIONE HCl |
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| Publication Number | Publication Date |
|---|---|
| CN108241030A true CN108241030A (en) | 2018-07-03 |
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ID=62701739
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611225836.7A Pending CN108241030A (en) | 2016-12-27 | 2016-12-27 | The assay method of compound I content in a kind of BUPROPIONE HCl |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111830151A (en) * | 2020-07-01 | 2020-10-27 | 迪沙药业集团有限公司 | Systematic applicability reference substance for quality control of bupropion hydrochloride composition |
-
2016
- 2016-12-27 CN CN201611225836.7A patent/CN108241030A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111830151A (en) * | 2020-07-01 | 2020-10-27 | 迪沙药业集团有限公司 | Systematic applicability reference substance for quality control of bupropion hydrochloride composition |
| CN111830151B (en) * | 2020-07-01 | 2021-05-04 | 迪沙药业集团有限公司 | Systematic applicability reference substance for quality control of bupropion hydrochloride composition |
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| PB01 | Publication | ||
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Application publication date: 20180703 |