CN103995062B - Method for testing exenatide and impurities thereof by using high performance liquid chromatography - Google Patents

Method for testing exenatide and impurities thereof by using high performance liquid chromatography Download PDF

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CN103995062B
CN103995062B CN201410205748.5A CN201410205748A CN103995062B CN 103995062 B CN103995062 B CN 103995062B CN 201410205748 A CN201410205748 A CN 201410205748A CN 103995062 B CN103995062 B CN 103995062B
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exenatide
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sodium
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彭忠华
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Holy Million Medicine Science And Technology Co Ltd In Zhejiang
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Abstract

The invention provides a method for testing exenatide and impurities of exenatide by using high performance liquid chromatography. When the exenatide and the impurities of the exenatide are tested by using the high performance liquid chromatography, the tests on the specificity, the linearity, the range, the recycling rate, the precision, the durability and the like of the impurities can be well performed. Eight impurities of confirmed structures are already separated by using the method provided by the invention. The method provided by the invention is reasonable in design, a widespread high performance liquid chromatograph is adopted as the instrument equipment, the flowing phase can be simply prepared, the detection cost is low, and separation and quantitative testing on the exenatide and the impurities of the exenatide are achieved.

Description

A kind of method of high effective liquid chromatography for measuring Exenatide and impurity thereof
Technical field
The invention belongs to analytical chemistry field, relate to the method analyzed and detect Exenatide and impurity thereof, be particularly effectively separated by a kind of high performance liquid chromatography and measure the method for Exenatide and impurity thereof.
Background technology
In Exenatide synthesis, place, in preparation technical process, the assorted peptide (i.e. Exenatide impurity) that some and Exenatide structures and characteristics are similar can be produced, such as, lack peptide, diastereo-isomerism etc.At present, the method being separated Exenatide and impurity thereof is often reversed-phased high performace liquid chromatographic and ion-exchange chromatography, but these existing disclosed reversed-phased high performace liquid chromatographic (mobile phase system acetonitrile: 0.1% trifluoroacetic acid solution etc.) methods are in Exenatide and impurity determination process thereof, specificity is poor, makes Exenatide and impurity (Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, D-His 1exenatide, Des-Gly 2exenatide) peak can not be separated or degree of separation does not reach requirement.
Summary of the invention
The object of this invention is to provide a kind of method of high effective liquid chromatography for measuring Exenatide and impurity thereof, be intended to solve Exenatide and impurity (Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, D-His 1exenatide, Des-Gly 2exenatide) separation quantitative measurement.
The present invention is realized by following steps:
1, the preparation of chromatographic column: the filling agent of chromatographic column used is for use octyl silane;
2, the setting of high performance liquid chromatograph: the determined wavelength of detecting device is 214nm, and auto injection actuator temperature is 6 DEG C, and column temperature is 40 DEG C, and flow rate of mobile phase is 0.8 ~ 1.2ml/min;
3, the configuration of chromatogram flow phase aqueous phase: take alkyl sodium sulfonate (sodium heptanesulfonate, sodium pentanesulfonate, sodium hexanesulfonate, perfluorooctane sulfonate, sodium nonanesulfonate, decane sulfonate) appropriate, by water-soluble solution and to be diluted to concentration summation be 1.2 ~ 1.8mmol/L solution, and adjust pH to 4.0 ~ 4.8 with phosphoric acid;
Described alkyl sodium sulfonate can be sodium heptanesulfonate, sodium pentanesulfonate, sodium hexanesulfonate, perfluorooctane sulfonate, sodium nonanesulfonate, decane sulfonate any one or multiple potpourri;
The concentration of described alkyl sodium sulfonate can be sodium heptanesulfonate, sodium pentanesulfonate, sodium hexanesulfonate, perfluorooctane sulfonate, sodium nonanesulfonate, one or more the concentration summation of potpourri of decane sulfonate;
4, the preparation of mobile phase: with acetonitrile-abovementioned alkyl sodium sulfonate solution (10:90) for mobile phase A, acetonitrile-abovementioned alkyl sodium sulfonate solution (52:48) is Mobile phase B;
5, adopt gradient elution, elution time and mobile phase A volume ratio program are 0.01 ~ 60 min from 60% → 25%, 60 ~ 60.5min moves to 65min from 25% → 60%, 60% again;
6, the configuration of sample solution: it is appropriate that precision takes sample, dissolves with mobile phase and is diluted to every ml about containing Exenatide 0.4 ~ 1.6mg/ml solution;
7, accurate pipette samples solution 40 μ l, inject hplc determination, and record chromatogram, in the chromatogram obtained, each impurity and main peak all reach good separation, the retention time of Exenatide is 26.272min, each impurity E xenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, D-His 1exenatide, Des-Gly 2the retention time of Exenatide is respectively: 8.787min, 10.935min, 12.109min, 13.085min, 23.204min, 24.855min, 28.458min, 29.407min, and relative retention time is respectively: 0.33,0.42,0.46,0.50,0.88,0.95,1.08,1.12.
The present invention, by rational method design, compared with existing method and technology, has obvious advantage: make the impurity of the structural identification of separation reach 8; The test such as the specificity of each impurity, linear and scope, the recovery, precision, durability is all good; Instrument and equipment is the high performance liquid chromatograph popularized; And mobile phase preparation is simple, testing cost is low.
Accompanying drawing explanation
Fig. 1 is Exenatide and each impurity liquid phase separation figure.
Embodiment
Below in conjunction with embodiment, the invention will be further described, but protection scope of the present invention is not limited to embodiment.
embodiment 1the process of establishing of the inventive method:
1, instrument and reagent
Instrument: Waters 2489 detecting device, Waters e2695 pump, Empower chromatographic work station;
Reagent: acetonitrile (chromatographically pure); Sodium heptanesulfonate, sodium pentanesulfonate, sodium hexanesulfonate, perfluorooctane sulfonate, sodium nonanesulfonate, decane sulfonate, trifluoroacetic acid, phosphoric acid (analyzing pure); Water for injection.
2, the foundation of Exenatide impurity determination method
(1) selection of wavelength: Exenatide and impurity (Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, D-His 1exenatide, Des-Gly 2exenatide) UV Absorption has the characteristic of self.We determine it at the absorption collection of illustrative plates of 25% acetonitrile solution under ultraviolet, Exenatide and each impurity thereof all have stronger uv absorption under 214nm wavelength, and therefore we select 214nm as the determined wavelength of this product.
(2) dissolubility test:
By the dissolubility contrast test of Exenatide in water and 25% acetonitrile, result shows: the solubleness of Exenatide in the acetonitrile of 25% can reach more than 1.6mg/ml, its impurity (Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, D-His 1exenatide, Des-Gly 2exenatide) in 25% acetonitrile, also can reach more than 0.5mg/ml, show, the requirement of the sensitivity of the mensuration of high-efficient liquid phase analysis can be met with 25% acetonitrile as analysis Exenatide and impurity thereof.
(3) the interference test of solvent:
Test solution after Exenatide and each impurity thereof being dissolved with 25% acetonitrile and solvent (25% acetonitrile) carry out test and comparison, judge whether selected solvent (25% acetonitrile) disturbs this to measure with this.
Method is as follows: get Exenatide and be about 10mg, accurately weighed, puts in 10ml measuring bottle, dissolves and be settled to scale with 25% acetonitrile, separately gets each impurity of Exenatide (Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, D-His 1exenatide, Des-Gly 2exenatide) appropriate, making concentration with 25% acetonitrile is the solution about containing each composition 10 μ g in every 1ml, as the need testing solution measuring Exenatide and impurity thereof.
Under above-mentioned chromatographic condition, get need testing solution and each 40 μ l of solvent (25% acetonitrile), injecting chromatograph, record chromatogram.
Result shows: Exenatide and impurity thereof is all good detecting of energy under this chromatographic condition, and all do not interfere with each other.Therefore, we adopt 25% acetonitrile as Exenatide and each impurity determination solvent.
(4) specificity of method
Separation under destructive (acid, alkali, hydrogen peroxide, heat, photo damage) test: get the appropriate about 10mg of Exenatide, 2 hours are destroyed (because this product is polypeptide drug under being placed in the condition of acid (0.1mol/ml HCl), alkali (0.1mol/ml NaOH), hydrogen peroxide (10%), heat 45 DEG C, light (4000L μ X), its to oxidation, heat, light is all more responsive, whole degradation time is shorter).Result shows that Exenatide all has degradation peak to produce under these conditions, and they and main peak all can reach good being separated.Therefore we think that this method has good specificity.
(5) with the comparing of existing method
After patent (CN103293255A, CN103424496A) is compared with this method: the amount of impurities of structural identification that method herein can be separated reaches 8 (see Fig. 1), not only isolate two impurity than original technology (CN103293255A) more, and have six impurity (Exenatide fragment3-39, Acetyl Exenatide, D-Ser 8exenatide, D-Ser 11exenatide, D-His 1exenatide, Des-Gly 2exenatide) be newly isolated; What original technology (CN103293255A) was used is the ultra-performance liquid chromatography not yet popularized, and technology is herein the high performance liquid chromatography popularized.
(6) sample introduction precision
Get each solution in Exenatide impurity determination, accurate absorption 40 μ l sample introductions, repeat 6 times, record each main peak area, calculate the method sample introduction precision.Result shows, the relative standard deviation of Exenatide and each impurity peak area thereof is all less than 2.0%, shows that the sample introduction precision of this method is good.
(7) recovery test of each impurity of Exenatide
Need testing solution: precision takes Exenatide and is about 10mg, is placed in the brown volumetric flask of 10ml by 9 parts, more corresponding precision adds each impurity reference substance mother liquor (impure Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, D-His 1exenatide, Des-Gly 2the concentration of Exenatide is about 100 μ g/ml) 0.5,1.0, each three parts of 1.5ml, with 25% acetonitrile dissolve and constant volume, for subsequent use.
Reference substance solution: accurate absorption Exenatide each impurity reference substance mother liquor (impure concentration is about 100 μ g/ml) 1.0ml, is placed in the brown volumetric flask of 10ml, 25% dilution in acetonitrile constant volume, for subsequent use.
Measure according to above-mentioned Exenatide and each impurity HPLC method thereof.Calculate, the results are shown in Table 1.
Above result shows: the present invention is to each impurity (D-Ser of Exenatide 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-His 1exenatide, Des-Gly 2exenatide) recovery measured is good.
(8) linear and scope
Precision measures reference substance mother liquor (the impure D-Ser of each impurity of Exenatide 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-His 1exenatide, Des-Gly 2the concentration of Exenatide is about 100 μ g/ml) 0.5,0.7,1.0,1.2,1.5,2.0ml, be placed in the brown volumetric flask of 10ml, with 25% dilution in acetonitrile constant volume, get 40 μ l sample introductions respectively, record peak area.Linear relationship between calculating concentration and peak area, obtains regression curve and regression equation.
Result shows: each impurity (D-Ser 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-His 1exenatide, Des-Gly 2exenatide) concentration is within the scope of 5 ~ 20 μ g/ml, and have good linear relationship between the peak area of each impurity of Exenatide and concentration, correlation coefficient r value is all greater than 0.9991.
(9) detectability and quantitative limit
By reference substance mother liquor (the impure D-Ser of each for Exenatide impurity 8exenatide, D-Ser 11exenatide, Met [O] Exenatide, Exenatide fragment3-39, Acetyl Exenatide, L-Glu 13exenatide, D-His 1exenatide, Des-Gly 2the concentration of Exenatide is about 100 μ g/ml) carry out stepwise dilution with 25% acetonitrile, injecting chromatograph, record peak height, concentration when each impurity peak height is 10 times high of baseline noise be quantitative limit concentration, 2 ~ 3 times high time concentration be detectability concentration, the quantitative limit of each impurity is: 25ng/ml; Quantitative limit is: 10ng/ml.
(10) method durability
in the methodological study and impurity determination of Exenatide impurity determination method, we once used different liquid phase instrument and the chromatographic column of different brands, and its result is unanimously.Therefore show that the durability of this method reaches requirement.
(11) stability of test solution
Get the test solution of Exenatide and each impurity thereof, place, respectively at different time sample introduction, record peak area, depending on its stability.Result shows: Exenatide and each test solution of relevant impurity thereof 8 time in peak area have no significant change, namely test solution is stable in 8 hours under the condition of this method.
detect by each impurity of following detection method to four batches of Exenatide samples.
embodiment 2measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V A).
Each impurity determination of Exenatide: be filling agent with octyl silane group silica gel, with acetonitrile-heptane sulfonic acid sodium salt (1.2mmol/L heptane sulfonic acid sodium salt, phosphoric acid adjusts pH to 4.0) (10:90) be mobile phase A, acetonitrile-heptane sulfonic acid sodium salt (52:48) is Mobile phase B, carries out gradient elution according to following table 2.
Determined wavelength is 214nm; Flow velocity 1.2ml/min; Auto injection actuator temperature is 6 DEG C; Column temperature is that the degree of separation at 40 DEG C of main peaks and assorted peak should meet the requirements.
The preparation of Exenatide need testing solution: get Exenatide sample appropriate (about containing Exenatide 10mg), accurately weighed, become concentration to be the solution about containing Exenatide 1mg in every 1ml with 25% acetontrile, shake up, for subsequent use.
Determination method: under chromatographic condition of the present invention, gets each 40 μ l of need testing solution, injecting chromatograph, and record chromatogram, calculates the content of Exenatide impurity with area normalization method.The results are shown in Table 3.
embodiment 3measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V A).
Each impurity determination of Exenatide: be filling agent with octyl silane group silica gel, with acetonitrile-heptane sulfonic acid sodium salt (1.8mmol/L heptane sulfonic acid sodium salt, phosphoric acid adjusts pH to 4.8) (10:90) be mobile phase A, acetonitrile-heptane sulfonic acid sodium salt (52:48) is Mobile phase B, carries out gradient elution according to following table 4.
Determined wavelength is 214nm; Flow velocity 1.2ml/min; Auto injection actuator temperature is 6 DEG C; Column temperature is that the degree of separation at 40 DEG C of main peaks and assorted peak should meet the requirements.
The preparation of Exenatide impurity need testing solution: get Exenatide sample appropriate (about containing Exenatide 10mg), accurately weighed, become concentration to be the solution about containing Exenatide 1mg in every 1ml with 25% acetontrile, shake up, for subsequent use.
Determination method: under chromatographic condition of the present invention, gets each 40 μ l of need testing solution, injecting chromatograph, and record chromatogram, calculates the content of the impurity of Exenatide with area normalization method.The results are shown in Table 5.
embodiment 4measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V A).
Each impurity determination of Exenatide: be filling agent with octyl silane group silica gel, with acetonitrile-decane sulfonic acid sodium solution (1.1mmol/L decane sulfonic acid sodium solution, phosphoric acid adjusts pH to 4.0) (10:90) be mobile phase A, acetonitrile-decane sulfonic acid sodium solution (52:48) is Mobile phase B, carries out gradient elution according to following table 6.
Determined wavelength is 214nm; Flow velocity 1.2ml/min; Auto injection actuator temperature is 6 DEG C; Column temperature is that the degree of separation at 40 DEG C of main peaks and assorted peak should meet the requirements.
The preparation of Exenatide impurity need testing solution: get Exenatide appropriate (about containing Exenatide 10mg), accurately weighed, become concentration to be the solution about containing Exenatide 1mg in every 1ml with 25% acetontrile, shake up, for subsequent use.
Determination method: under chromatographic condition of the present invention, gets each 40 μ l of need testing solution, injecting chromatograph, and record chromatogram, calculates the content of the impurity of Exenatide with area normalization method.The results are shown in Table 7.
embodiment 5measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V A).
Each impurity determination of Exenatide: be filling agent with octyl silane group silica gel, with acetonitrile-decane sulfonic acid sodium solution (1.8mmol/L decane sulfonic acid sodium solution, phosphoric acid adjusts pH to 4.8) (10:90) be mobile phase A, acetonitrile-decane sulfonic acid sodium solution (52:48) is Mobile phase B, carries out gradient elution according to following table 8.
Determined wavelength is 214nm; Flow velocity 1.2ml/min; Auto injection actuator temperature is 6 DEG C; Column temperature is that the degree of separation at 40 DEG C of main peaks and assorted peak should meet the requirements.
The preparation of Exenatide impurity need testing solution: get Exenatide sample appropriate (about containing Exenatide 10mg), accurately weighed, become concentration to be the solution about containing Exenatide 1mg in every 1ml with 25% acetontrile, shake up, for subsequent use.
Determination method: under chromatographic condition of the present invention, gets each 40 μ l of need testing solution, injecting chromatograph, and record chromatogram, calculates the content of the impurity of Exenatide with area normalization method.The results are shown in Table 9.
embodiment 6high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V A) measures.
Each impurity determination of Exenatide: be filling agent with octyl silane group silica gel, with acetonitrile-alkyl sodium sulfonate mixed solution (0.25mmol/L sodium heptanesulfonate, 0.25mmol/L sodium pentanesulfonate, 0.25mmol/L sodium hexanesulfonate, 0.25mmol/L perfluorooctane sulfonate, 0.25mmol/L sodium nonanesulfonate, 0.25mmol/L decane sulfonate mixed solution, phosphoric acid adjusts pH to 4.2) (10:90) be mobile phase A, acetonitrile-alkyl sodium sulfonate mixed solution (52:48) is Mobile phase B, carries out gradient elution according to table 10.
Determined wavelength is 214nm; Flow velocity 1.2ml/min; Auto injection actuator temperature is 6 DEG C; Column temperature is that the degree of separation at 40 DEG C of main peaks and assorted peak should meet the requirements.
The preparation of Exenatide impurity need testing solution: get Exenatide sample appropriate (about containing Exenatide 10mg), accurately weighed, become concentration to be the solution about containing Exenatide 1mg in every 1ml with 25% acetontrile, shake up, for subsequent use.
Determination method: under chromatographic condition of the present invention, gets each 40 μ l of need testing solution, injecting chromatograph, and record chromatogram, calculates the content of the impurity of Exenatide with area normalization method.The results are shown in following table 11.
embodiment 7high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V A) measures.
Each impurity determination of Exenatide: be filling agent with octyl silane group silica gel, with acetonitrile-heptane sulfonic acid sodium salt (1.5mmol/L heptane sulfonic acid sodium salt, phosphoric acid adjusts pH to 3.9) (10:90) be mobile phase A, acetonitrile-heptane sulfonic acid sodium salt (52:48) is Mobile phase B, carries out gradient elution according to table 12.
Determined wavelength is 214nm; Flow velocity 1.2ml/min; Auto injection actuator temperature is 6 DEG C; Column temperature is that the degree of separation at 40 DEG C of main peaks and assorted peak should meet the requirements.
The preparation of Exenatide impurity need testing solution: get Exenatide sample appropriate (about containing Exenatide 10mg), accurately weighed, become concentration to be the solution about containing Exenatide 1mg in every 1ml with 25% acetontrile, shake up, for subsequent use.
Determination method: under chromatographic condition of the present invention, gets each 40 μ l of need testing solution, injecting chromatograph, and record chromatogram, calculates the content of the impurity of Exenatide with area normalization method.The results are shown in Table 13.
Result: the peak of Exenatide and other impurity peaks degree of separation can not reach the requirement of Chinese Pharmacopoeia, therefore cannot draw the correct result of impurity.
embodiment 8high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V A) measures.
Each impurity determination of Exenatide: be filling agent with octyl silane group silica gel, with acetonitrile-heptane sulfonic acid sodium salt (1.9mmol/L heptane sulfonic acid sodium salt, phosphoric acid adjusts pH to 4.7) (10:90) be mobile phase A, acetonitrile-heptane sulfonic acid sodium salt (52:48) is Mobile phase B, carries out gradient elution according to table 14.
Determined wavelength is 214nm; Flow velocity 1.2ml/min; Auto injection actuator temperature is 6 DEG C; Column temperature is that the degree of separation at 40 DEG C of main peaks and assorted peak should meet the requirements.
The preparation of Exenatide impurity need testing solution: get Exenatide sample appropriate (about containing Exenatide 10mg), accurately weighed, become concentration to be the solution about containing Exenatide 1mg in every 1ml with 25% acetontrile, shake up, for subsequent use.
Determination method: under chromatographic condition of the present invention, gets each 40 μ l of need testing solution, injecting chromatograph, and record chromatogram, calculates the content of the impurity of Exenatide with area normalization method.
Result: main peak retention time is about 45 minutes, the relative retention time of impurity peaks is about 0.93.The peak of Exenatide and other impurity peaks degree of separation can not reach the requirement of Chinese Pharmacopoeia.Therefore the correct result of impurity cannot be drawn.
As can be seen from embodiment 1-5 and embodiment 6-7(comparing embodiment) result: the inventive method is simple, and can reach again the requirement of Chinese Pharmacopoeia, obviously be better than published technology, therefore the method is more suitable for the mensuration of Exenatide and impurity thereof.

Claims (2)

1. a method for high effective liquid chromatography for measuring Exenatide and impurity thereof, is characterized in that, is realized by following steps:
(1) preparation of chromatographic column: the filling agent of chromatographic column used is for use octyl silane;
(2) setting of high performance liquid chromatograph: the determined wavelength of detecting device is 214nm, and auto injection actuator temperature is 6 DEG C, and column temperature is 40 DEG C, and flow rate of mobile phase is 0.8 ~ 1.2ml/min;
(3) configuration of chromatogram flow phase aqueous phase: take alkyl sodium sulfonate, by water-soluble solution and to be diluted to concentration summation be 1.2 ~ 1.8mmol/L solution, and adjusts pH to 4.0 ~ 4.8 with phosphoric acid;
(4) preparation of mobile phase: mobile phase A is acetonitrile-abovementioned alkyl sodium sulfonate solution=10 :90, Mobile phase B is acetonitrile -alkyl sulfonic acid sodium solution=52 :48;
(5) gradient elution: elution time and mobile phase A volume ratio order are 0 ~ 60 min from 60% → 25%, 60 ~ 60.5min moves to 65min from 25% → 60%, 60% again;
(6) configuration of sample solution: take sample, dissolves with mobile phase and is diluted to containing Exenatide 0.4 ~ 1.6mg/ml solution;
(7) accurate pipette samples solution 40 μ l, injects hplc determination, and records chromatogram, the retention time of Exenatide is 26.272min, the relative retention time of each impurity is respectively: Exenatide fragment3-39:0.33, Acetyl Exenatide:0.42, L-Glu 13exenatide:0.46, D-Ser 8exenatide:0.50, D-Ser 11exenatide:0.88, Met [O] Exenatide:0.95, D-His 1exenatide:1.08, Des-Gly 2exenatide:1.12.
2. the method for a kind of high effective liquid chromatography for measuring Exenatide according to claim 1 and impurity thereof, it is characterized in that, the alkyl sodium sulfonate described in step (3) selects one or more the potpourri in sodium heptanesulfonate, sodium pentanesulfonate, sodium hexanesulfonate, perfluorooctane sulfonate, sodium nonanesulfonate or decane sulfonate.
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