CN104614451B - A kind of diethylene glycol methyl propionate detection method - Google Patents
A kind of diethylene glycol methyl propionate detection method Download PDFInfo
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- CN104614451B CN104614451B CN201410739263.4A CN201410739263A CN104614451B CN 104614451 B CN104614451 B CN 104614451B CN 201410739263 A CN201410739263 A CN 201410739263A CN 104614451 B CN104614451 B CN 104614451B
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- diethylene glycol
- methyl propionate
- detection method
- glycol methyl
- acrylic acid
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Abstract
The present invention relates to a kind of diethylene glycol methyl propionate detection method, described detection method comprises the following steps: prepare standard substance；Titer is prepared；Draw standard curve；Measure: testing sample solution is injected ion exclusion high performance liquid chromatography and detects, reference standard curve, carry out peak area quantification calculating according to quota ion.The present invention is quick, and easy, accurately, mild condition is easily operated, can be used for PEG trace and semimicrodetermination, can apply to PEG dressing agent and the assay of PEG modified medicaments and quality control.
Description
Technical field
The present invention relates to a kind of detection method, particularly relate to a kind of quick, easy, diethylene glycol methyl propionate inspection accurately
Survey method.
Background technology
Polyethylene Glycol (PEG) is albumen and the minimum polymer of cell absorption level in hitherto known polymer, by
In the biocompatibility that PEG is nontoxic and good, it is that by chemical method, the PEG of activation is coupled to medicine that the PEG of medicine modifies
On process, physicochemical property and the biologic activity of medicine can be improved after PEGization, improve pharmacokinetics and drug effect etc. property
Matter, is obviously enhanced dissolubility and the stability of medicine, reduces immunogenicity and antigenicity, reduces toxic and side effects, adds internal
The effect such as biological activity and curative effect, this technology has started to be applied to protein (peptides), enzyme, antibody and small-molecule drug
In.
This dressing agent is widely used in modification research and the application of various kinds of drug, and Present Domestic is outer to polyethyleneglycol modified dose
Detection analysis have not been reported.The present invention, according to the architectural characteristic of diethylene glycol methyl propionate dressing agent, uses ion row
Resistance high performance liquid chromatography carries out quantitative detecting analysis.
Summary of the invention
The invention provides a kind of quick, easy, diethylene glycol methyl propionate detection method accurately.
In order to realize above-mentioned mesh ground, the present invention by the following technical solutions:
A kind of diethylene glycol methyl propionate detection method, described detection method comprises the following steps:
A) prepare standard substance stock solution: weigh diethylene glycol methyl propionate 95-105mg, be dissolved in water and constant volume 1000mL,
Obtain Standard Reserving Solution, preserve at 0-4 DEG C；
B) titer preparation: respectively aspiration step 1) obtain standard reserving solution 1,2,3,4,5mL is in 100mL volumetric flask
In, add water constant volume；
3) standard curve is drawn: the titer of step b) is carried out the most successively according to concentration ion exclusion high-efficient liquid
Phase chromatograph detects and draws standard curve；
4) measure: draw testing sample 1mL and add pure water to be diluted to concentration be 1-5 μ g/mL, then testing sample solution is noted
Enter ion exclusion high performance liquid chromatography to detect, reference standard curve, carry out peak area quantification calculating according to quota ion.This
Quickly, easy, accurately, mild condition is easily operated, can be used for PEG trace and semimicrodetermination, can apply to PEG and repaiies in invention
Adorn agent and the assay of PEG modified medicaments and quality control.
As preferably, the structural formula of diethylene glycol methyl propionate is:。
As preferably, diethylene glycol methyl propionate be prepared under catalyst action by diethylene glycol and acrylic acid methyl ester. and
Becoming, preparation condition is: pressure 0.1-0.8Mpa, reaction temperature 1-220 DEG C.
As preferably, diethylene glycol is 1:1-1.85 with the mass ratio of acrylic acid methyl ester..
As preferably, solvent be the one in ether, ethanol, acetone, acetonitrile, catalyst be nano catalyst, nanometer
One or more in silver catalyst, cerium oxide, nano magnesia, the consumption of solvent is diethylene glycol and the total matter of acrylic acid methyl ester.
The 10-20% of amount.
As preferably, diethylene glycol and acrylic acid methyl ester. before starting reaction, first ultrasonic vibration 1-3 hour, ultrasonic power
For 65-85kw, vibrations add catalyst after half an hour, and the consumption of catalyst is diethylene glycol and acrylic acid methyl ester. gross mass
0.5-1.1%。
As preferably, the testing conditions of ion exclusion high performance liquid chromatography is: chromatographic column: Bio-radHPX-87H (5um,
300mmx7.8mm)；Flowing phase: pH1.0 3.0 sulfuric acid solution, flow velocity: 0.4-1.2mL/min；Sample size is 20uL；Column temperature
40-60℃；Using UV-detector, detection wavelength is 190-220nm.
Beneficial effects of the present invention: the present invention is quick, easy, accurately, mild condition is easily operated, can be used for PEG trace
With semimicrodetermination, can apply to PEG dressing agent and the assay of PEG modified medicaments and quality control.
Accompanying drawing explanation
Fig. 1 is the chromatographic fractionation figure of embodiment 1.
In figure, 1, diethylene glycol (reactant)；2, methyl propionate (reactant)；3, reaction dissolvent；4, by-product dimerization
Body；5, diethylene glycol methyl propionate.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further explained:
Embodiment 1
Prepare diethylene glycol methyl propionate: join in ether by diethylene glycol and acrylic acid methyl ester., first ultrasonic vibration half
Adding catalyst nano gold after hour, ultrasonic power is 65-85kw, then proceedes to vibrate 1.5 hours, at pressure 0.1Mpa, instead
Answering temperature 10 DEG C to start reaction, the response time is 5 hours.Wherein, the consumption of nanometer gold is that diethylene glycol is total with acrylic acid methyl ester.
The 0.5% of quality, the consumption of ether is the 10% of diethylene glycol and acrylic acid methyl ester. gross mass, diethylene glycol and acrylic acid methyl ester.
Mass ratio is 1:1.
Diethylene glycol methyl propionate dressing agent detects:
A) prepare standard substance stock solution: weigh diethylene glycol methyl propionate 100mg, be dissolved in water and constant volume 1000mL,
To Standard Reserving Solution, preserve at 4 DEG C；
B) titer preparation: respectively aspiration step 1) obtain standard reserving solution 1,2,3,4,5mL is in 100mL volumetric flask
In, add water constant volume；
3) standard curve is drawn: the titer of step b) is carried out the most successively according to concentration ion exclusion high-efficient liquid
Phase chromatograph detects and draws standard curve；
4) measure: draw testing sample 1mL and add pure water to be diluted to concentration be 1-5 μ g/mL, then testing sample solution is noted
Enter ion exclusion high performance liquid chromatography to detect, reference standard curve, carry out peak area quantification calculating according to quota ion.Its
In, the testing conditions of ion exclusion high performance liquid chromatography is: chromatographic column: Bio-radHPX-87H (5um, 300mmx7.8mm)；Stream
Dynamic phase: pH1.0 sulfuric acid solution, flow velocity: 0.4mL/min；Sample size is 20uL；Column temperature 50 DEG C；Use UV-detector, detect ripple
A length of 220nm.
Embodiment 2
Prepare diethylene glycol methyl propionate: join in ethanol by diethylene glycol and acrylic acid methyl ester., first ultrasonic vibration half
Adding catalyst nano silver after hour, ultrasonic power is 65-85kw, then proceedes to vibrate half an hour, in pressure 0.5Mpa, reaction
Temperature 180 DEG C starts reaction, and the response time is 8 hours.Wherein, the consumption of nanometer silver is diethylene glycol and the total matter of acrylic acid methyl ester.
The 0.8% of amount, the consumption of ethanol is the 15% of diethylene glycol and acrylic acid methyl ester. gross mass, diethylene glycol and the matter of acrylic acid methyl ester.
Amount ratio is 1:1.2.
Diethylene glycol methyl propionate dressing agent detects:
A) prepare standard substance stock solution: weigh diethylene glycol methyl propionate 100mg, be dissolved in water and constant volume 1000mL,
To Standard Reserving Solution, preserve at 4 DEG C；
B) titer preparation: respectively aspiration step 1) obtain standard reserving solution 1,2,3,4,5mL is in 100mL volumetric flask
In, add water constant volume；
3) standard curve is drawn: the titer of step b) is carried out the most successively according to concentration ion exclusion high-efficient liquid
Phase chromatograph detects and draws standard curve；
4) measure: draw testing sample 1mL and add pure water to be diluted to concentration be 1-5 μ g/mL, then testing sample solution is noted
Enter ion exclusion high performance liquid chromatography to detect, reference standard curve, carry out peak area quantification calculating according to quota ion.Its
In, the testing conditions of ion exclusion high performance liquid chromatography is: chromatographic column: Bio-radHPX-87H (5um, 300mmx7.8mm)；Stream
Dynamic phase: pH2.0 sulfuric acid solution, flow velocity: 0.8mL/min；Sample size is 20uL；Column temperature 60 DEG C；Use UV-detector, detect ripple
A length of 200nm.
Embodiment 3
Prepare diethylene glycol methyl propionate: join in acetonitrile by diethylene glycol and acrylic acid methyl ester., first ultrasonic vibration half
Adding catalyst cerium oxide and nano magnesia after hour, ultrasonic power is 65-85kw, then proceedes to vibrate 2.5 hours, in pressure
Power 0.8Mpa, reaction temperature 220 DEG C starts reaction, and the response time is 10 hours.Wherein, cerium oxide and the consumption of nano magnesia
Respectively accounting for half for diethylene glycol with the 1.1% of acrylic acid methyl ester. gross mass, cerium oxide and nano magnesia, the consumption of acetonitrile is two
Ethylene glycol and the 20% of acrylic acid methyl ester. gross mass, diethylene glycol is 1:1.85 with the mass ratio of acrylic acid methyl ester..
Diethylene glycol methyl propionate dressing agent detects:
A) prepare standard substance stock solution: weigh diethylene glycol methyl propionate 100mg, be dissolved in water and constant volume 1000mL,
To Standard Reserving Solution, preserve at 4 DEG C；
B) titer preparation: respectively aspiration step 1) obtain standard reserving solution 1,2,3,4,5mL is in 100mL volumetric flask
In, add water constant volume；
3) standard curve is drawn: the titer of step b) is carried out the most successively according to concentration ion exclusion high-efficient liquid
Phase chromatograph detects and draws standard curve；
4) measure: draw testing sample 1mL and add pure water to be diluted to concentration be 1-5 μ g/mL, then testing sample solution is noted
Enter ion exclusion high performance liquid chromatography to detect, reference standard curve, carry out peak area quantification calculating according to quota ion.Its
In, the testing conditions of ion exclusion high performance liquid chromatography is: chromatographic column: Bio-radHPX-87H (5um, 300mmx7.8mm)；Stream
Dynamic phase: pH3.0 sulfuric acid solution, flow velocity: 1.2mL/min；Sample size is 20uL；Column temperature 40 DEG C；Use UV-detector, detect ripple
A length of 190nm.
The structural formula of diethylene glycol methyl propionate is。
With reference to Fig. 1, reactant retention time is respectively 9.00min and 10.3min, and solvent peak reaches 12.1min three
Baseline separation, by-product retention time 14.2min, product diethylene glycol methyl propionate is that 16.93min two component also obtains good
Good baseline separation.Solvent and by-product are not reaching to baseline separation, and a middle also unknown peak, but to product diethyl two
The external standard method of alcohol methyl propionate does not affect.Draw standard curve linearly dependent coefficient R2=0.992, average recovery
98.8-100.5%, its lowest detection is limited to 0.53ug/mL(S/N=3), detection precision is 0.51%.
Peak area (R good with concentration linear relationship2> 0.99), institute's construction method is quick, and easy, accurately, mild condition is prone to
Operation, can be used for PEG trace and semimicrodetermination, can apply PEG dressing agent and the assay of PEG modified medicaments and quality
Control.
Claims (3)
1. a diethylene glycol methyl propionate detection method, it is characterised in that described detection method comprises the following steps:
A) prepare standard substance stock solution: weigh diethylene glycol methyl propionate 95-105mg, be dissolved in water and constant volume 1000mL, obtain
Standard Reserving Solution, preserves at 0-4 DEG C；
B) titer preparation: respectively aspiration step 1) obtain standard reserving solution 1,2,3,4,5mL in 100mL volumetric flask, add
Water constant volume；
3) standard curve is drawn: the titer of step b) is carried out the most successively according to concentration ion exclusion high-efficient liquid phase color
Spectrum detection also draws standard curve；
4) measure: draw testing sample 1mL add pure water to be diluted to concentration be 1-5 μ g/mL, then by testing sample solution inject from
Sub-Exclusion High Performance liquid chromatograph detects, reference standard curve, carries out quantitative Analysis according to quota ion peak area size；Its
In, the structural formula of diethylene glycol methyl propionate is:；
Diethylene glycol methyl propionate is prepared from acrylic acid methyl ester. by diethylene glycol under catalyst action, preparation condition
For: pressure 0.1-0.8Mpa, reaction temperature 10-220 DEG C；Diethylene glycol is 1:1-1.85 with the mass ratio of acrylic acid methyl ester.；Two
Ethylene glycol and acrylic acid methyl ester. join in solvent, and before starting reaction, first ultrasonic vibration 1-3 hour, ultrasonic power is 65-
85kw, vibrations add catalyst after half an hour, and the consumption of catalyst is the 0.5-of diethylene glycol and acrylic acid methyl ester. gross mass
1.1%；The testing conditions of ion exclusion high performance liquid chromatography is: chromatographic column: Bio-radHPX-87H300mmx7.8mm, 5um；Stream
Dynamic phase: pH1.0 sulfuric acid solution, flow velocity: 0.4mL/min；Sample size is 20uL；Column temperature 50 DEG C；Use UV-detector, detect ripple
A length of 220nm.
A kind of diethylene glycol methyl propionate detection method the most according to claim 1, it is characterised in that solvent be ether,
One in ethanol, acetone, acetonitrile, catalyst are in nano catalyst, nano-silver catalyst, cerium oxide, nano magnesia
One or more, the consumption of solvent is the 10-20% of diethylene glycol and acrylic acid methyl ester. gross mass.
A kind of diethylene glycol methyl propionate detection method the most according to claim 1, it is characterised in that ion exclusion is efficient
The testing conditions of liquid chromatograph is: chromatographic column: Bio-radHPX-87H300mmx7.8mm, 5um；Flowing phase: pH1.0 sulphuric acid is molten
Liquid, flow velocity: 0.4mL/min；Sample size is 20uL；Column temperature 50 DEG C；Using UV-detector, detection wavelength is 220nm.
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