CN107656005A - Separation and assay method of the erlotinib Hydrochloride with potential impurity - Google Patents
Separation and assay method of the erlotinib Hydrochloride with potential impurity Download PDFInfo
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- G—PHYSICS
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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
- G01N30/02—Column chromatography
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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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- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/884—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample organic compounds
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Abstract
The invention belongs to analytical chemistry field, and in particular to separation and assay method of the erlotinib Hydrochloride to related potential impurity.This method is using octadecylsilane chemically bonded silica as stationary phase, eluted using methanol acetonitrile mixed liquor and phosphate-buffered salt as mobile phase, this method can realize erlotinib Hydrochloride and 10 kinds of related potential impurity while efficiently separate, this method also carries out separation determination using high performance liquid chromatography, not only realize and efficiently separate, can also Accurate Determining erlotinib Hydrochloride and related potential impurity content, specificity is strong, high sensitivity, it is extremely important for quality control of the realization to erlotinib Hydrochloride, safety.
Description
Technical field
The invention belongs to analytical chemistry field, and in particular to the separation and survey of erlotinib Hydrochloride and related potential impurity
Determine method.
Background technology
Erlotinib Hydrochloride is tyrosine kinase inhibitor, after previously receiving at least one chemotherapy regimen failure
Locally Advanced or transfer non-small cell lung cancer.Erlotinib Hydrochloride it is Chinese entitled：N- (3- acetylene phenyl) -6,7- is double
(2- methoxyethoxies) -4- quinoline amine hydrochlorates, English are entitled：Erlotinib hydrochloride, its structural formula such as formula I
It is shown：
In the building-up process of erlotinib Hydrochloride, it synthesizes raw material K, the J used, and building-up process produces accessory substance
A, B, D, E, F, G, H, I, the impurity contained in these erlotinib Hydrochlorides for all making finally to obtain, these related potential impurity
Structural formula is as follows：
In order to control the quality of erlotinib Hydrochloride, it is necessary to be separated to erlotinib Hydrochloride and its related potential impurity
Measure.But there is presently no the HPLC methods of 10 potential impurity of separation determination erlotinib Hydrochloride and the above simultaneously.Therefore
A kind of method of 10 potential impurity of separation determination erlotinib Hydrochloride and the above is developed for realizing to erlotinib Hydrochloride
Quality control, safety are extremely important.
The content of the invention
In view of this, it is an object of the invention to provide a kind of while separate the side of erlotinib Hydrochloride and potential impurity
Method, this method can realize efficiently separating for erlotinib Hydrochloride and its potential impurity.Present invention also offers utilize efficient liquid
The method of phase chromatography separation determination erlotinib Hydrochloride and potential impurity, this method are not only realized and efficiently separated, additionally it is possible to accurate
The really content of measure erlotinib Hydrochloride and potential impurity, specificity is strong, high sensitivity, for realizing to erlotinib Hydrochloride
Quality control, safety are extremely important.
To achieve the above object, the technical scheme is that：
The method for separating erlotinib Hydrochloride and potential impurity, using octadecylsilane chemically bonded silica as stationary phase, with first
Alcohol-acetonitrile mixture and phosphate-buffered salt are that mobile phase is eluted, and the structural formula of the erlotinib Hydrochloride is as shown in formula I；
Further, described method, the potential impurity are one kind in compound shown in A, B, D, E, F, G, H, I, J, K
It is or a variety of；
Preferably, the method for present invention separation erlotinib Hydrochloride and potential impurity, to erlotinib Hydrochloride and the above 10
The potential impurity of kind is separated simultaneously.
Further, described method, the phosphate-buffered salt are the mixed liquor of potassium dihydrogen phosphate aqueous solution and diethylamine, institute
The volume ratio for stating potassium dihydrogen phosphate aqueous solution and diethylamine is 1000：1-3, the potassium dihydrogen phosphate aqueous solution concentration are 1-
1.5g/1000ml。
Preferably, the volume ratio of the potassium dihydrogen phosphate aqueous solution and diethylamine is 1000：2, the potassium dihydrogen phosphate water
Solution concentration is 1.36g/1000ml.
Further, described method, the pH value of the phosphate-buffered salt is 3.0-3.2.
Preferably, the pH value of the phosphate-buffered salt is 3.1.
In the present invention, the phosphate-buffered salt can be prepared using following methods：
Potassium dihydrogen phosphate 1g-1.5g is taken, is dissolved in water and is diluted to 1000ml, add diethylamine solution 1.0ml-
3.0ml, mix, pH value is adjusted to 3.0-3.2 with phosphoric acid solution.
Further, described method, the volume ratio of the methanol and acetonitrile is 0.8-1.2：1.
Preferably, the volume ratio of the methanol and acetonitrile is 1：1.
Further, described method, the volume ratio of the methanol-acetonitrile mixed liquor and phosphate-buffered salt is 30-70：30-
70。
Preferably, the mobile phase is separated using linear gradient elution, and linear gradient elution condition is：
0min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35；
20min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 55-65：35-45；
30min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 60-70：30-40；
50min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 55-65：35-45；
60min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 25-35：65-75；
62min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35；
70min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35.
It is furthermore preferred that linear gradient elution condition is：
0min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 70：30；
20min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 60：40；
30min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65：35；
50min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 60：40；
60min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 30：70；
62min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 70：30；
70min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 70：30.
Present invention also offers the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
This method is not only realized and efficiently separated, additionally it is possible to which the content of Accurate Determining erlotinib Hydrochloride and potential impurity, specificity is strong, spirit
Sensitivity is high.
Utilize the method for high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity, the high-efficient liquid phase color
Spectrometry uses chromatographic column of the octadecylsilane chemically bonded silica for filler, using methanol-acetonitrile mixed liquor and phosphate-buffered salt as
Mobile phase carries out elution separation, and erlotinib Hydrochloride and potential impurity are detected using UV-detector after separation；It is described
Phosphate-buffered salt is the mixed liquor of potassium dihydrogen phosphate aqueous solution and diethylamine, the body of the potassium dihydrogen phosphate aqueous solution and diethylamine
Product is than being 1000：1-3, the potassium dihydrogen phosphate aqueous solution concentration are 1-1.5g/1000ml；The volume ratio of the methanol and acetonitrile
For 0.8-1.2：1.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
The potential impurity is the one or more in compound shown in A, B, D, E, F, G, H, I, J, K.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
The mobile phase is separated using linear gradient elution, and linear gradient elution condition is：
0min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35；
20min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 55-65：35-45；
30min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 60-70：30-40；
50min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 55-65：35-45；
60min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 25-35：65-75；
62min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35；
70min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35.
It is furthermore preferred that linear gradient elution condition is：
0min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 70：30；
20min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 60：40；
30min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65：35；
50min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 60：40；
60min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 30：70；
62min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 70：30；
70min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 70：30.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
The specification of the chromatographic column is 4.6 × 250mm, 5 μm.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
The flow velocity of the mobile phase is 0.5-1.5ml/min.
Preferably, the flow velocity of the mobile phase is 1.0ml/min.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
The chromatographic column column temperature is 30 DEG C ± 5 DEG C.
Preferably, the chromatographic column column temperature is 30 DEG C.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
Ultraviolet detection wavelength is 247nm ± 5nm.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
Described method is specially：
Take potential impurity reference substance to add diluent dissolving to be prepared into the reference substance solution of concentration known, take test sample to add dilution
Agent dissolving is prepared into need testing solution, takes reference substance solution and need testing solution sample introduction respectively, carries out efficient liquid phase chromatographic analysis,
Chromatogram is recorded, compares the peak area that need testing solution corresponds to the impurity of appearance time with reference substance solution, calculates test sample
In the content of contained Tarceva and potential impurity；The diluent is acetonitrile solution, and the volume ratio of wherein acetonitrile and water is
0.8-1.2：1.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
The sample size is 20 μ l.
Further, the method using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity,
Methods described also comprises the following steps：Erlotinib Hydrochloride and potential impurity reference substance are taken respectively, are dissolved make with diluent respectively
The positioning solution of solution and each potential impurity is positioned into Tarceva, carries out efficient liquid phase chromatographic analysis, determine Tarceva and
The retention time of each potential impurity.
In one particular embodiment of the present invention, using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride with
The method of potential impurity concretely comprises the following steps：
(1) impurity reference substance solution：It is appropriate that precision weighs each impurity reference substance, adds diluent to dissolve and quantifies dilution and is made
About each μ g of impure reference substance 0.3 mixed solution in per 1ml.
(2) need testing solution：Test sample about 50mg is taken, it is accurately weighed, put in 50ml measuring bottles, add diluent to be diluted to quarter
Degree, shakes up, produces；
(3) assay method：Setting flow rate of mobile phase is 1.0ml/min, takes the above-mentioned μ l sample introductions of solution 20 respectively, records chromatogram
Figure, compare the peak area of need testing solution and impurity in reference substance solution；The diluent uses acetonitrile solution, acetonitrile and water
Volume ratio be 1：1.
The beneficial effects of the present invention are：
(1) method of of the invention separation erlotinib Hydrochloride and potential impurity, using octadecylsilane chemically bonded silica as
Stationary phase, eluted using methanol-acetonitrile mixed liquor and phosphate-buffered salt as mobile phase, realize erlotinib Hydrochloride to it is related
Potential impurity efficiently separates.
(2) present invention utilizes the method for high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity, detection
During, solvent peak does not disturb the measure of erlotinib Hydrochloride and potential impurity, this method not only realize erlotinib Hydrochloride with
10 potential impurity efficiently separates, additionally it is possible to which the content of Accurate Determining erlotinib Hydrochloride and potential impurity, specificity is strong, spirit
Sensitivity is high, and successfully solve erlotinib Hydrochloride and its 10 potential impurity efficiently separates problem, and then realizes impurity and have
Effect control, fundamentally ensure that product quality, have for quality control of the realization to erlotinib Hydrochloride, safety
Extremely important meaning.
Brief description of the drawings
Fig. 1 schemes for the diluent HPLC of embodiment 1.
Fig. 2 schemes for the impurity I reference substances HPLC of embodiment 1, and the chromatographic peak in Fig. 2 is the chromatographic peak of impurity I reference substances, is retained
Time is in 5.2min or so.
Fig. 3 schemes for the impurity K reference substances HPLC of embodiment 1, and the chromatographic peak in Fig. 3 is the chromatographic peak of impurity K reference substances, is retained
Time is in 7.1min or so.
Fig. 4 schemes for the impurity J reference substances HPLC of embodiment 1, and the chromatographic peak in Fig. 4 is the chromatographic peak of impurity J reference substances, is retained
Time is in 11.3min or so.
Fig. 5 schemes for the impurity E reference substance HPLC of embodiment 1, and the chromatographic peak in Fig. 5 is the chromatographic peak of impurity E reference substance, is retained
Time is in 17.8min or so.
Fig. 6 schemes for the test sample HPLC of embodiment 1, and the chromatographic peak in Fig. 6 is the chromatographic peak of test sample, and retention time exists
27.9min or so.
Fig. 7 schemes for the impurity A reference substance HPLC of embodiment 1, and the chromatographic peak in Fig. 7 is the chromatographic peak of impurity A reference substance, is retained
Time is in 44.0min or so.
Fig. 8 schemes for the impurity B reference substance HPLC of embodiment 1, and the chromatographic peak in Fig. 8 is the chromatographic peak of impurity B reference substance, is retained
Time is in 47.6min or so.
Fig. 9 schemes for the impurity G reference substances HPLC of embodiment 1, and the chromatographic peak in Fig. 9 is the chromatographic peak of impurity G reference substances, is retained
Time is in 54.0min or so.
Figure 10 schemes for the impurity H reference substances HPLC of embodiment 1, and the chromatographic peak in Figure 10 is the chromatographic peak of impurity H reference substances, is protected
The time is stayed in 56.5min or so.
Figure 11 schemes for the impurity D reference substances HPLC of embodiment 1, and the chromatographic peak in Figure 11 is the chromatographic peak of impurity D reference substances, is protected
The time is stayed in 60.8min or so.
Figure 12 schemes for the impurity F reference substance HPLC of embodiment 1, and the chromatographic peak in Figure 12 is the chromatographic peak of impurity F reference substance, is protected
The time is stayed in 64.4min or so.
Figure 13 is the mixed solution HPLC of embodiment 1 figures, the chromatographic peak in Figure 13 is I, K, J, E, Tarceva, A, B, G, H,
D, F chromatographic peak, retention time are followed successively by：5.2min、7.1min、11.4min、17.8min、27.9min、44.3min、
47.7min、54.3min、56.7min、60.8min、64.4min。
Figure 14 is that (figure is that hydrochloric acid strategic point is with the addition of in impurity reference substance solution to the impurity reference substance solution HPLC of embodiment 1 figures
Buddhist nun is replaced in Lip river, can be not added with during sample).
Figure 15 is that the HPLC that detection is analyzed using method 1 is schemed.
Figure 16 is that the HPLC that detection is analyzed using method 2 is schemed.
Figure 17 is that the HPLC that detection is analyzed using method 3 is schemed.
Figure 18 is that the HPLC that detection is analyzed using method 4 is schemed.
Figure 19 is that the HPLC that detection is analyzed using method 5 is schemed.
Embodiment
Illustrated embodiment is to preferably be illustrated to present disclosure, but is not that present disclosure only limits
In illustrated embodiment.So those skilled in the art carry out nonessential change according to foregoing invention content to embodiment
Enter and adjust, in addition to any combination between each embodiment, still fall within protection scope of the present invention.
Involved sample, reference substance source are as shown in the table in embodiment：
Embodiment 1
1st, instrument and condition
Instrument：High performance liquid chromatograph；
Chromatographic column：Agilent Eclipse XDB C18 (4.6 × 250mm, 5 μm)；
Mobile phase：By progress linear gradient elution table 1 Suo Shi；
A：Phosphate-buffered salt (takes potassium dihydrogen phosphate 1.36g, is dissolved in water and is diluted to 1000ml, add diethylamine solution
2.0ml, mix, pH value is adjusted to 3.1 ± 0.1 with phosphoric acid solution)；
B：Methanol-acetonitrile (volume ratio 1：1)；
The gradient elution table of table 1
UV-detector Detection wavelength：247nm；
Flow velocity：1.0ml/min；
Column temperature：30℃；
Sample size：20μl；
Diluent：Acetonitrile solution (volume ratio 1：1).
2nd, experimental procedure
(1) each impurity positioning solution：It is appropriate that precision weighs each impurity reference substance, puts in different measuring bottles, respectively plus dilution
The solution that about each μ g of impure reference substance 100 in every 1ml are made in dilution is dissolved and quantified in agent.
(2) impurity reference substance solution：It is appropriate that precision pipettes each impurity positioning solution, puts in same measuring bottle, adds diluent molten
Solve and quantify the mixed solution that about each μ g of impure reference substance 0.3 in every 1ml are made in dilution.
(3) need testing solution：Test sample about 50mg is taken, it is accurately weighed, put in 50ml measuring bottles, add diluent to be diluted to quarter
Degree, shakes up, produces；
(4) mixed solution：Test sample about 50mg is weighed, it is appropriate to pipette each impurity positioning solution respectively, puts same 50ml amounts
In bottle, add diluent to be diluted to scale, shake up, produce.
(5) assay method：Take diluent, each impurity positioning solution respectively, need testing solution, impurity reference substance solution and mixed
Each 20 μ l sample introductions of solution are closed, efficient liquid phase chromatographic analysis is carried out by above-mentioned chromatographic condition, records chromatogram, compare need testing solution
With the peak area of each impurity in reference substance solution.
3rd, testing result
Chromatogram is shown in Fig. 1-14, and disturbed specimen does not determine for plain dilution agent it can be seen from Fig. 1-14；Main peak with it is neighbouring miscellaneous
Separating degree meets the requirements between mass peak；The peak-to-peak separating degree of each known impurities is met the requirements, and it is respectively less than miscellaneous that impurity is detected in test sample
The peak area of corresponding impurity in matter reference substance.
The comparison of the method and existing analysis method of the present invention of embodiment 2
Sour Tarceva is uncharged in Ch.P, USP and EP, therefore refers to erlotinib Hydrochloride piece country import drugs note
Related substance method (referring to the method 1-3 of table 2) in volume standard JX20080202, but the method is not controlled to known impurities
System.
The method 4 of table 2 is bibliography《5 kinds of Qualitative and quantitative analysis about material in erlotinib Hydrochloride and its tablet》
[from《Pharmaceutical Analysis magazine》5th phase in 2015] described in method.
The method 5 of table 2 is method of the invention.
The Related substance method of table 2
Above-mentioned 5 kinds of methods are respectively adopted separation detection, the chromatogram of method 1 are carried out to erlotinib Hydrochloride and potential impurity
As shown in figure 15, the chromatogram of method 2 is as shown in figure 16, and the chromatogram of method 3 is as shown in figure 17, and the chromatogram of method 4 is as schemed
Shown in 18, the chromatogram of method 5 is as shown in figure 19, and the analysis result of each method is as shown in table 3.
The analysis result table of the Related substance method of table 3
As a result show：Using the method for import related preparations, impurity D and impurity G are completely overlapped, impurity H and impurity D/G's
Separating degree is 0.98, and the separating degree between impurity A and impurity B is 0.66.The method of import related preparations is adjusted, impurity D
It is still completely overlapped with impurity G, and non-appearance in impurity F 50min.Using literature method (method 4), impurity H and impurity G point
It is 0.9 from degree, impurity D and impurity F are completely overlapped.Using the HPLC methods (method 5) of the present invention, between all impurity and impurity with
Separating degree is all higher than 1.5 between main peak, and each chromatographic peak peak type is preferable, therefore uses the HPLC methods of the present invention to survey relevant material
Fixed, method of the invention can control in synthesis technique (catabolite) in (raw material, accessory substance etc.) or storage to draw
Enter the impurity in finished product, be extremely important for quality control of the realization to erlotinib Hydrochloride, safety.
Finally illustrate, the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although with reference to compared with
The present invention is described in detail good embodiment, it will be understood by those within the art that, can be to the skill of the present invention
Art scheme is modified or equivalent substitution, and without departing from the objective and scope of technical solution of the present invention, it all should cover at this
Among the right of invention.
Claims (10)
1. separate the method for erlotinib Hydrochloride and potential impurity, it is characterised in that using octadecylsilane chemically bonded silica be solid
Determine phase, eluted using methanol-acetonitrile mixed liquor and phosphate-buffered salt as mobile phase, the structural formula of the erlotinib Hydrochloride is such as
Shown in formula I；
2. according to the method for claim 1, it is characterised in that the potential impurity is A, B, D, E, F, G, H, I, J, K institute
Show the one or more in compound；
3. according to the method for claim 1, it is characterised in that the phosphate-buffered salt is potassium dihydrogen phosphate aqueous solution and two
The mixed liquor of ethamine, the volume ratio of the potassium dihydrogen phosphate aqueous solution and diethylamine is 1000：1-3, the potassium dihydrogen phosphate water
Solution concentration is 1-1.5g/1000ml.
4. according to the method for claim 1, it is characterised in that the volume ratio of the methanol and acetonitrile is 0.8-1.2：1.
5. according to the method for claim 1, it is characterised in that the body of the methanol-acetonitrile mixed liquor and phosphate-buffered salt
Product ratio is 30-70：30-70.
6. utilize the method for high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity, it is characterised in that described
High performance liquid chromatography uses chromatographic column of the octadecylsilane chemically bonded silica for filler, with methanol-acetonitrile mixed liquor and
Phosphate-buffered salt is that mobile phase carries out elution separation, and erlotinib Hydrochloride and potential impurity are entered using UV-detector after separation
Row detection；The phosphate-buffered salt is the mixed liquor of potassium dihydrogen phosphate aqueous solution and diethylamine, the potassium dihydrogen phosphate aqueous solution
Volume ratio with diethylamine is 1000：1-3, the potassium dihydrogen phosphate aqueous solution concentration are 1-1.5g/1000ml；The methanol with
The volume ratio of acetonitrile is 0.8-1.2：1.
7. the side according to claim 6 using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity
Method, it is characterised in that the potential impurity is the one or more in compound shown in A, B, D, E, F, G, H, I, J, K.
8. the side according to claim 6 using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity
Method, it is characterised in that the mobile phase is separated using linear gradient elution, and linear gradient elution condition is：
0min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35；
20min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 55-65：35-45；
30min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 60-70：30-40；
50min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 55-65：35-45；
60min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 25-35：65-75；
62min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35；
70min：The volume ratio of phosphate-buffered salt and methanol-acetonitrile mixed liquor is 65-75：25-35.
9. the side according to claim 6 using high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity
Method, it is characterised in that ultraviolet detection wavelength is 247nm ± 5nm.
10. according to claim 6 utilize high efficiency liquid chromatography for separating and determining erlotinib Hydrochloride and potential impurity
Method, it is characterised in that described method is specially：
Take potential impurity reference substance to add diluent dissolving to be prepared into the reference substance solution of concentration known, take test sample to add diluent molten
Solution is prepared into need testing solution, takes reference substance solution and need testing solution sample introduction respectively, carries out efficient liquid phase chromatographic analysis, record
Chromatogram, compare the peak area that need testing solution corresponds to the impurity of appearance time with reference substance solution, calculate institute in test sample
Content containing Tarceva and potential impurity；The diluent is acetonitrile solution, and wherein the volume ratio of acetonitrile and water is 0.8-
1.2：1.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109574940A (en) * | 2018-11-20 | 2019-04-05 | 成都新恒创药业有限公司 | A kind of degradation impurity and its preparation, detection method and application of erlotinib Hydrochloride |
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