CN107870208A - The detection method of residues of formaldehyde in a kind of bisulfate clopidogrel - Google Patents
The detection method of residues of formaldehyde in a kind of bisulfate clopidogrel Download PDFInfo
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- CN107870208A CN107870208A CN201610857515.2A CN201610857515A CN107870208A CN 107870208 A CN107870208 A CN 107870208A CN 201610857515 A CN201610857515 A CN 201610857515A CN 107870208 A CN107870208 A CN 107870208A
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- 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
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Abstract
The invention discloses a kind of detection of residues of formaldehyde in bisulfate clopidogrel.Method includes following steps：（1）The configuration of derivatization reagent, 2,4 dinitrophenylhydrazine acetonitrile solutions（5%）With 0.1mol/L hydrochloric acid；（2）Solvent（Methanol：Water=1:9）Preparation；（3）The configuration of blank solvent,（4）The configuration of reference substance solution, the formaldehyde reference substance storing solution of high concentration is first configured, progressively dilutes, obtains 20ng/ml reference substance solution；（5）500mg samples are first weighed, add derivatization reagent and 0.1mol/L hydrochloric acid；（6）Blank solvent, reference substance solution and sample solution are placed in 2 3h in 50 DEG C of 60 DEG C of isothermal vibration casees, is let cool after taking-up to room temperature, solubilizer and is diluted to scale, shaken up；（7）Detection.
Description
Technical field
The present invention relates to a kind of detection of residues of formaldehyde in bisulfate clopidogrel, belongs to genotoxicity impurity residue detection
Technical field.
Background technology
Formaldehyde (formaldehyde) is gas that is colourless, having excitant and asphyxiating, and commodity are its aqueous solution.Yi Rong
Most organic solvents such as the Yishui River, ethanol.Formaldehyde property is stable, is a kind of important Organic Ingredients, and dyestuff, medicine, agricultural chemicals
Raw material etc..
Formaldehyde is noxious material, and research shows, formaldehyde easily chemically reacts with cell nucleophile, forms chemical combination
Thing, causes DNA damage, and formaldehyde is classified as suspect carcinogen by international cancer mechanism；Formaldehyde exposure limit:Chinese MAC is 3mg/
M3, U.S. TWA-OSHA are 3ppm.
In the synthesis technique of bisulfate clopidogrel, the residual of formaldehyde is had, it is therefore desirable to develop a kind of method, determine
The residual of formaldehyde in bisulfate clopidogrel.
The content of the invention
It is an object of the invention to provide a kind of sensitivity is low, residues of formaldehyde in repeated good bisulfate clopidogrel
Detection method.
The present invention is achieved by the following technical solutions：
The detection of residues of formaldehyde, includes following steps in a kind of bisulfate clopidogrel：
（1）Derivatization reagent is prepared：
DNPH acetonitrile solution（Concentration 5%）：Precision weighs 25mg DNPH reference substance in 100ml
In volumetric flask, after adding appropriate acetonitrile dissolving, scale is settled to dilution in acetonitrile, after shaking uniformly, precision pipettes the 5ml solution
It is placed in 50ml volumetric flasks, after being settled to scale with dilution in acetonitrile, shakes up standby.
0.1mol/L hydrochloric acid：Precision pipettes 9ml hydrochloric acid in 100ml volumetric flasks, is diluted with water and is settled to scale；It is accurate
Above-mentioned solution 10ml is pipetted in 100ml volumetric flasks, is diluted with water and is settled to scale.
（2）Solvent is prepared：Solvent（Methanol：Water=1:9）：100ml methanol and 900ml water are measured respectively, are well mixed.
（3）Blank solvent：Precision pipettes 30ml solvents in 50ml volumetric flasks, adds 5ml DNPH second
Nitrile solution（Concentration 5%）With 0.1mol/L hydrochloric acid 10ml.
（4）Reference substance solution：Precision weighs the 55.6mg formaldehyde reference substance aqueous solution in the 100ml containing 10ml or so water
In volumetric flask, after being diluted with water, scale is settled to, is shaken up, be designated as reference substance storing solution #1；Precision pipette 1ml storing solutions #1 in
In 100ml volumetric flasks, scale is diluted with water to, after shaking up, is denoted as reference substance storing solution #1；Precision pipettes 5ml storing solutions #2
In 50ml volumetric flasks, 25ml solvents are added, add 5ml DNPH acetonitrile solution（Concentration 5%）, Ran Houzai
0.1mol/L hydrochloric acid 10ml are added, are shaken up rear closed
（5）Sample solution：Precision weighs 500mg bisulfate clopidogrels in 50ml volumetric flasks, after adding 5ml methanol to dissolve, then
25ml water is added, then adds 5ml DNPH acetonitrile solution（Concentration 5%）With 0.1mol/L hydrochloric acid 10ml, shake up
It is closed afterwards.
（6）Derivatization：Above-mentioned blank solvent, reference substance solution and sample solution are placed in 50 DEG C of -60 DEG C of isothermal vibration casees
Middle 2-3h, let cool after taking-up to room temperature, solubilizer and be diluted to scale, shaken up.
（7）Detection：Detected using HPLC, testing conditions are using C18 posts, specification 3.0*100mm, Detection wavelength
For 367nm, mobile phase uses volume ratio as 4:6 acetonitrile and 0.01mol/L aqueous hydrochloric acid solutions, flow velocity 0.7ml/min.
The detection method of residues of formaldehyde, derivatization reagent DNPH in a kind of described bisulfate clopidogrel
Concentration be 5%.
The making of standard curve：After taking formaldehyde reference substance storing solution #2 and derivatization reagent derivatization, dilution is configured to
40ng/ml, 30ng/ml, 20ng/ml, 10ng/ml and 5ng/ml standard liquid, are detected using HPLC, and testing conditions are
Volume ratio is used as 4 using C18 posts, specification 3.0*100mm, Detection wavelength 367nm, mobile phase:6 acetonitrile and
0.01mol/L aqueous hydrochloric acid solutions, flow velocity 0.7ml/min.Obtained numerical value and concentration are depicted as standard curve.
Determination of recovery rates：2ml, 1ml and 0.5ml formaldehyde reference substance are separately added into bisulfate clopidogrel sample solution
Storing solution #2, is configured to 40ng/ml, 20ng/ml and 10ng/ml rate of recovery solution, while prepares blank solvent, sample solution
And contrast solution, calculate the rate of recovery.
The beneficial effect that the present invention is reached：
The detection method of the present invention is simple to operation, and sensitivity is low, favorable reproducibility；Appearance time is 3.0min；It is computed,
Linear relationship is good in the range of 5ng/mL-40ng/mL, correlation coefficient r 0.9985, the rate of recovery of three concentration from low to high
Respectively 84.6%, 89.5% and 95.1%.
Embodiment
With reference to embodiment, the invention will be further described.
Embodiment 1：
In the present embodiment, the detection of residues of formaldehyde in a kind of bisulfate clopidogrel, including following steps：
（1）Derivatization reagent is prepared：
DNPH acetonitrile solution（Concentration 5%）：Precision weighs 25mg DNPH reference substance in 100ml
In volumetric flask, after adding appropriate acetonitrile dissolving, scale is settled to dilution in acetonitrile, after shaking uniformly, precision pipettes the 5ml solution
It is placed in 50ml volumetric flasks, after being settled to scale with dilution in acetonitrile, shakes up standby.
0.1mol/L hydrochloric acid：Precision pipettes 9ml hydrochloric acid in 100ml volumetric flasks, is diluted with water and is settled to scale；It is accurate
Above-mentioned solution 10ml is pipetted in 100ml volumetric flasks, is diluted with water and is settled to scale.
（2）Solvent is prepared：Solvent（Methanol：Water=1:9）：100ml methanol and 900ml water are measured respectively, are well mixed.
（3）Blank solvent：Precision pipettes 30ml solvents in 50ml volumetric flasks, adds 5ml DNPH second
Nitrile solution（Concentration 5%）With 0.1mol/L hydrochloric acid 10ml.
（4）Reference substance solution：Precision weighs the 55.6mg formaldehyde reference substance aqueous solution in the 100ml containing 10ml or so water
In volumetric flask, after being diluted with water, scale is settled to, is shaken up, be designated as reference substance storing solution #1；Precision pipette 1ml storing solutions #1 in
In 100ml volumetric flasks, scale is diluted with water to, after shaking up, is denoted as reference substance storing solution #1；Precision pipettes 5ml storing solutions #2
In 50ml volumetric flasks, 25ml solvents are added, add 5ml DNPH acetonitrile solution（Concentration 5%）, Ran Houzai
0.1mol/L hydrochloric acid 10ml are added, are shaken up rear closed
（5）Sample solution：Precision weighs 500mg bisulfate clopidogrels in 50ml volumetric flasks, after adding 5ml methanol to dissolve, then
25ml water is added, then adds 5ml DNPH acetonitrile solution（Concentration 5%）With 0.1mol/L hydrochloric acid 10ml, shake up
It is closed afterwards.
（6）Derivatization：Above-mentioned blank solvent, reference substance solution and sample solution are placed in 2h in 60 DEG C of isothermal vibration casees,
Let cool after taking-up to room temperature, solubilizer and be diluted to scale, shaken up.
（7）Detection：Detected using HPLC, testing conditions are using C18 posts, specification 3.0*100mm, Detection wavelength
For 367nm, mobile phase uses volume ratio as 4:6 acetonitrile and 0.01mol/L aqueous hydrochloric acid solutions, flow velocity 0.7ml/min.
Embodiment 2：
In the present embodiment, the detection of residues of formaldehyde in a kind of bisulfate clopidogrel, including following steps：
（1）Derivatization reagent is prepared：
DNPH acetonitrile solution（Concentration 5%）：Precision weighs 25mg DNPH reference substance in 100ml
In volumetric flask, after adding appropriate acetonitrile dissolving, scale is settled to dilution in acetonitrile, after shaking uniformly, precision pipettes the 5ml solution
It is placed in 50ml volumetric flasks, after being settled to scale with dilution in acetonitrile, shakes up standby.
0.1mol/L hydrochloric acid：Precision pipettes 9ml hydrochloric acid in 100ml volumetric flasks, is diluted with water and is settled to scale；It is accurate
Above-mentioned solution 10ml is pipetted in 100ml volumetric flasks, is diluted with water and is settled to scale.
（2）Solvent is prepared：Solvent（Methanol：Water=1:9）：100ml methanol and 900ml water are measured respectively, are well mixed.
（3）Blank solvent：Precision pipettes 30ml solvents in 50ml volumetric flasks, adds 5ml DNPH second
Nitrile solution（Concentration 5%）With 0.1mol/L hydrochloric acid 10ml.
（4）Reference substance solution：Precision weighs the 55.6mg formaldehyde reference substance aqueous solution in the 100ml containing 10ml or so water
In volumetric flask, after being diluted with water, scale is settled to, is shaken up, be designated as reference substance storing solution #1；Precision pipette 1ml storing solutions #1 in
In 100ml volumetric flasks, scale is diluted with water to, after shaking up, is denoted as reference substance storing solution #1；Precision pipettes 5ml storing solutions #2
In 50ml volumetric flasks, 25ml solvents are added, add 5ml DNPH acetonitrile solution（Concentration 5%）, Ran Houzai
0.1mol/L hydrochloric acid 10ml are added, are shaken up rear closed
（5）Sample solution：Precision weighs 500mg bisulfate clopidogrels in 50ml volumetric flasks, after adding 5ml methanol to dissolve, then
25ml water is added, then adds 5ml DNPH acetonitrile solution（Concentration 5%）With 0.1mol/L hydrochloric acid 10ml, shake up
It is closed afterwards.
（6）Derivatization：Above-mentioned blank solvent, reference substance solution and sample solution are placed in 3h in 50 DEG C of isothermal vibration casees,
Let cool after taking-up to room temperature, solubilizer and be diluted to scale, shaken up.
（7）Detection：Detected using HPLC, testing conditions are using C18 posts, specification 3.0*100mm, Detection wavelength
For 367nm, mobile phase uses volume ratio as 4:6 acetonitrile and 0.01mol/L aqueous hydrochloric acid solutions, flow velocity 0.7ml/min.
Claims (8)
- A kind of 1. detection of residues of formaldehyde in bisulfate clopidogrel, it is characterized in that DNPH acetonitrile solution concentration 1%-15%, preferably detectable concentration are 5%.
- 2. the detection of residues of formaldehyde in a kind of bisulfate clopidogrel according to claim 1, wherein solvent are methanol, second The mixture of alcohol, propyl alcohol, acetic acid and water, volume ratio 1:5—1：9, preferably methanol：Water=1:9.
- 3. detection method according to claim 1, reference substance solution scope is the ug/ml of 0.1 ug/ml -1.0, preferably 0.5 ug/ml。
- 4. detection method Detection wavelength according to claim 1 is 330nm -380nm, preferably Detection wavelength is 367nm.
- 5. detection method according to claim 1, flow and be for acetonitrile, propionitrile, normal propyl alcohol and aqueous hydrochloric acid solution, volume ratio 1:5—5:6, preferably select 2:3.
- 6. detection method flow velocity according to claim 1 is 0.4ml/min -1.1ml/min, preferable flow rate 0.7ml/ min。
- 7. the detection of residues of formaldehyde in a kind of bisulfate clopidogrel according to claim 1, it is characterized in that derivatization For condition to be placed in 20 DEG C of -80 DEG C of isothermal vibration casees, preferable temperature is 50 DEG C -60 DEG C.
- 8. detection method according to claim 1, the time is that 1-5h is suitable, preferably 2-3h in isothermal vibration case.
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| CN201610857515.2A CN107870208A (en) | 2016-09-28 | 2016-09-28 | The detection method of residues of formaldehyde in a kind of bisulfate clopidogrel |
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| CN201610857515.2A CN107870208A (en) | 2016-09-28 | 2016-09-28 | The detection method of residues of formaldehyde in a kind of bisulfate clopidogrel |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110763777A (en) * | 2019-11-06 | 2020-02-07 | 宁夏启元药业有限公司 | Method for detecting residual formaldehyde in azithromycin |
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2016
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110763777A (en) * | 2019-11-06 | 2020-02-07 | 宁夏启元药业有限公司 | Method for detecting residual formaldehyde in azithromycin |
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