CN106770723B - A kind of detection method of the dolasetron mesilate injection in relation to substance - Google Patents
A kind of detection method of the dolasetron mesilate injection in relation to substance Download PDFInfo
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- 229960003413 dolasetron Drugs 0.000 title claims abstract description 65
- CGHRJBLSXVCYQF-YXSUXZIUSA-N dolasetron Chemical compound C1=CC=C[C]2C(C(O[C@@H]3C[C@@H]4C[C@@H]5C[C@@H](N4CC5=O)C3)=O)=CN=C21 CGHRJBLSXVCYQF-YXSUXZIUSA-N 0.000 title claims abstract description 63
- 238000002347 injection Methods 0.000 title claims abstract description 58
- 239000007924 injection Substances 0.000 title claims abstract description 58
- 239000000126 substance Substances 0.000 title claims abstract description 46
- 238000001514 detection method Methods 0.000 title claims abstract description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 28
- 230000015556 catabolic process Effects 0.000 claims abstract description 25
- 238000006731 degradation reaction Methods 0.000 claims abstract description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000010828 elution Methods 0.000 claims abstract description 5
- 239000000945 filler Substances 0.000 claims abstract description 4
- 125000000524 functional group Chemical group 0.000 claims abstract description 4
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 16
- 239000012488 sample solution Substances 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- 239000000872 buffer Substances 0.000 claims description 10
- 229910019142 PO4 Inorganic materials 0.000 claims description 9
- 238000010790 dilution Methods 0.000 claims description 8
- 239000012895 dilution Substances 0.000 claims description 8
- 238000005259 measurement Methods 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 8
- 239000010452 phosphate Substances 0.000 claims description 8
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 4
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical group [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
- 239000008351 acetate buffer Substances 0.000 claims description 2
- UKTAZPQNNNJVKR-KJGYPYNMSA-N chembl2368925 Chemical compound C1=CC=C2C(C(O[C@@H]3C[C@@H]4C[C@H]5C[C@@H](N4CC5=O)C3)=O)=CNC2=C1 UKTAZPQNNNJVKR-KJGYPYNMSA-N 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000388 diammonium phosphate Inorganic materials 0.000 claims description 2
- 235000019838 diammonium phosphate Nutrition 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 claims 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 27
- 229940079593 drug Drugs 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 6
- 238000004811 liquid chromatography Methods 0.000 abstract description 2
- 230000005526 G1 to G0 transition Effects 0.000 abstract 1
- FGDQGIKMWOAFIK-UHFFFAOYSA-N acetonitrile;phosphoric acid Chemical compound CC#N.OP(O)(O)=O FGDQGIKMWOAFIK-UHFFFAOYSA-N 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000012071 phase Substances 0.000 description 22
- 238000012360 testing method Methods 0.000 description 18
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 14
- 238000000926 separation method Methods 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 6
- 229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 5
- 102000035037 5-HT3 receptors Human genes 0.000 description 4
- 108091005477 5-HT3 receptors Proteins 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000010977 jade Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 238000005220 pharmaceutical analysis Methods 0.000 description 2
- 238000005498 polishing Methods 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 230000001515 vagal effect Effects 0.000 description 2
- 210000002348 5-ht neuron Anatomy 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 102100034159 Beta-3 adrenergic receptor Human genes 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
- 101000671819 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 36 Proteins 0.000 description 1
- 102100040109 Ubiquitin carboxyl-terminal hydrolase 36 Human genes 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 210000003818 area postrema Anatomy 0.000 description 1
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 108091008690 chemoreceptors Proteins 0.000 description 1
- 229960003218 dolasetron mesylate Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002322 enterochromaffin cell Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000009863 impact test Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- VWDWKYIASSYTQR-YTBWXGASSA-N sodium;dioxido(oxo)azanium Chemical compound [Na+].[O-][15N+]([O-])=O VWDWKYIASSYTQR-YTBWXGASSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- QTFFGPOXNNGTGZ-RCSCTSIBSA-N u3c8e5bwkr Chemical compound O.CS(O)(=O)=O.C1=CC=C2C(C(OC3C[C@@H]4CC5C[C@@H](N4CC5=O)C3)=O)=CNC2=C1 QTFFGPOXNNGTGZ-RCSCTSIBSA-N 0.000 description 1
Classifications
-
- 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
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses a kind of high-efficiency liquid chromatography method for detecting of the dolasetron mesilate injection in relation to substance, use the stationary phase of Silica Surface bonding C8 functional group for filler chromatographic column, using mixture of acetonitrile-phosphate buffer-methanol and acetonitrile as dual-flow phase, gradient elution, this method can quickly and effectively separate the main preparation process impurity of dolasetron mesilate injection and degradation impurity.A kind of quickly and effectively detection method is provided for the related substance of prosecution dolasetron mesilate injection, to guarantee dolasetron mesilate injection products quality and drug safety.
Description
Technical field
The invention belongs to Pharmaceutical Analysis detection fields, and in particular to a kind of related substance of dolasetron mesilate injection
High-efficiency liquid chromatography method for detecting.
Background technique
5-HT3 receptor antagonist is applied to nausea and vomiting caused by treatment chemotherapy, and mechanism, which is that chemotherapy is practical, can lead to
5-HT largely is discharged from intestinal mucosa enterochromaffin cell, so that the supraneural 5-HT3 receptor of stimulation vagal afferents of specificity, makes
Afferent vagal impulse increases, while under the action of chemotherapeutics, discharges with the 5-HT neuron of local cerebral area postrema
5-HT, then the 5-HT3 receptor of chemoreceptor trigger zone is stimulated to generate impulsion, trigger gag reflex.Due to 5-HT3 receptor antagonist
The structure of agent is extremely similar to 5-HT, vomiting reflex caused by 5-HT can be prevented to rush with the emulative combination 5-HT3 receptor of 5-HT
Dynamic conduction.Therefore, 5-HT3 receptor antagonist prevents the 5-HT3 receptor of periphery and maincenter effectively by competition receptor to press down
System or the generation for reducing nausea and vomiting reflection.Efficiently, tolerance is good for 5-HT3 receptor antagonist one kind drug itself simultaneously,
The advantages that being side effect outside no centrum.
Dolasetron mesilate is a kind of 5-HT3 receptor antagonist, it is potent and have high selectivity, to other 5-HT
Receptor, α or Beta-3 adrenergic receptor, dopamine receptor etc. is without obvious effect.Tolerance is good, and LD50 value is high, and safety is good,
More guarantee that it has a vast market foreground in clinical application.
But according to FDA: dolasetron mesilate injection (Dolasetron Mesylate Injection) tool
There is the side effect of apparent cardiac rhythm, and its tablet has good safety.During sample detection, injection is found
It is middle that there are the specific impurities that principal component and mannitol generate.The related substance of Dolasetron bulk pharmaceutical chemicals has only been included in USP36
Detection method, and the USP method can not effectively detect the specific impurities.Yang Xiuli etc. is in " domestic methanesulfonic acid Duola department
The Primary Study of measurement and its stability of the fine jade in relation to substance " in (Pharmaceutical Analysis magazine, 2008,28 (1)) by USP method slightly
It improves, still retains the dual-flow phase containing acetonitrile, it is broken to carry out high temperature, high humidity, acid, alkali to dolasetron mesilate injection
It is detected after bad, because not detecting special impurities, it is thus regarded that high temperature has no shadow to dolasetron mesilate injection
It rings.Patent CN201110295660.3 also provides similar detection method, detects to the injection under each prescription, but still
Dolasetron mesilate can be enhanced in the increase for failing to detect new peculiar impurity, and think polyhydroxy substance such as mannitol etc.
The stability of injection.It was found by the inventors of the present invention that dolasetron mesilate can not be infused well using existing method
The some special relative substances penetrated in liquid are separated and be detected, thus influence the judgement and control to impurity.
Therefore the present invention can make up for it the spy that dolasetron mesilate injection generates in actual production and storage
Determine impurity to be tested and analyzed well, to guarantee that the quality of dolasetron mesilate injection products and the safety of patient are used
Medicine.So the present invention detects and controls the related substance of dolasetron mesilate injection has practical value very much.
Summary of the invention
In view of during production and storage, there may be with cardiac rhythm side effect for dolasetron mesilate injection
Special relative substance, and existing method, including USP (United States Pharmacopeia) method cannot provide and efficiently separate and detect this and have
The method for closing impurity, the purpose of the present invention is to provide a kind of high-efficient liquid phase color of the dolasetron mesilate injection in relation to substance
Spectrum detection method can effectively detect the special related substance of dolasetron mesilate injection, to guarantee Drug safety, matter
Measure controllability.
Above-mentioned purpose of the invention is achieved through the following technical solutions:
A kind of detection method of the dolasetron mesilate injection in relation to substance, this method is high performance liquid chromatography,
It is characterized in that, chromatographic condition are as follows: using the filler of Silica Surface bonding C8 functional group as chromatographic column fixed phase；With pH be 6.5~
7.5 buffer-acetonitrile is mobile phase A, and the volume ratio of buffer and acetonitrile is (900~1100): (50~56) are with methanol
Gradient elution is carried out according to the following table in Mobile phase B:
Some specific embodiments according to the present invention, the gradient elution are carried out according to the following table:
The filler of Silica Surface bonding C8 functional group is chromatographic column fixed phase, and preferred chromatographic column is ZORBAX
SB C8 column (250 × 4.6mm).
Preferably, the volume ratio of buffer and acetonitrile is (900~1100): (50~56), more preferably 1000:53.
Preferably, the pH of buffer is 6.8~7.0.
According to some embodiments of the present invention, the buffer is phosphate buffer or acetate buffer.
The phosphate is preferably sodium dihydrogen phosphate or diammonium hydrogen phosphate, in some embodiments of the invention, with
The sodium hydroxide tune pH to 6.5~7.5 of the sodium dihydrogen phosphate of 0.01mol/L 1mol/L, more preferably adjust pH to 6.8~
7.0, the volume ratio of buffer and acetonitrile is 1000:53.
According to some embodiments of the present invention, flow rate of mobile phase is 1.0ml/min~2.0ml/min, preferably 1.5ml/
min；Wherein the column temperature of chromatographic column is 20~30 DEG C, preferably 25 DEG C；For UV detector, Detection wavelength is the detector used
200nm~220nm, preferably 210nm.
In one embodiment of the invention, a kind of detection of the dolasetron mesilate injection in relation to substance is provided
Method, specific step is as follows
A) takes dolasetron mesilate injection that about dolasetron mesilate is made in every 1ml with 20% dilution in acetonitrile
6.25mg sample solution；
B) is made in every 1ml about after taking 150 DEG C of dolasetron mesilate injection destructions 5 hours with 20% dilution in acetonitrile
Dolasetron mesilate 6.25mg high temperature degradation solution；
C) takes 100 μ l of solution a), b), injects liquid chromatograph, measures by the chromatographic condition, records chromatogram,
Complete the measurement in relation to substance.
The related substance of dolasetron mesilate injection is mainly impurity, and the present invention uses high performance liquid chromatography C8 column
It is separated, using the mobile phase and elution program for being different from existing method and USP method, realizes the effective of impurity
Separation.And accelerate the degradation of dolasetron mesilate injection to increase degradation impurity by high temperature, to investigate the special of the method for the present invention
Attribute.
High temperature accelerated test of the invention destroys dolasetron mesilate injection 5 hours at 150 DEG C, with of the invention
Detection method finds that its relative substance obviously increases, and method of the invention has in sample solution and accelerated degradation solution
It the separation of effect and detects the indissociable impurity of existing method (referring to the impurity 1-6 in attached drawing 1-7), it is seen that methanesulfonic acid Duola
Department fine jade injection be not it is heat stable, the condition and detection means of accelerated test have a major impact testing result.Due to
The limitation of existing method can not efficiently separate and detect impurity 1-6 in dolasetron mesilate injection, therefore cannot
Research and effectively control are carried out to the impurity, also influence the correctness of the guidance of drug stock control.
By comparative test, method of the invention detects to be efficiently separated and detected using art methods
Impurity, this influences the factor of dolasetron mesilate injection quality on determining, so as to adjust dolasetron mesilate injection
Production technology and storage condition, reduce impurity content in final products, guarantee that product quality and patient medication have safely ten
Divide important meaning.
Detailed description of the invention
Fig. 1 is that 1 dolasetron mesilate injection of embodiment is schemed in relation to the HPLC of substance；
Fig. 2 is that 1 dolasetron mesilate injection high temperature degradation of embodiment is schemed in relation to the HPLC of substance；
Fig. 3 is that the lower dolasetron mesilate injection of comparative test 1 is schemed in relation to the HPLC of substance；
Fig. 4 is that the lower dolasetron mesilate injection high temperature degradation of comparative test 1 is schemed in relation to the HPLC of substance；
Fig. 5 is that the lower dolasetron mesilate injection high temperature degradation of comparative test 2 is schemed in relation to the HPLC of substance；
Fig. 6 is that the lower dolasetron mesilate injection high temperature degradation of comparative test 3 is schemed in relation to the HPLC of substance；
Fig. 7 is that the lower dolasetron mesilate injection high temperature degradation of comparative test 4 is schemed in relation to the HPLC of substance.
Specific embodiment
It is clear to be more clear the object, technical solutions and advantages of the present invention, With reference to embodiment to this
Aspect is further described in detail.
Embodiment 1
Detecting instrument and chromatographic condition
Detecting instrument: Shimadzu LC-20AT high performance liquid chromatograph
Chromatographic condition: chromatographic column is ZORBAX SB C8 column (250 × 4.6mm), and chromatographic column column temperature is 25 DEG C, and use is ultraviolet
Detector, Detection wavelength are set as 210nm；Flow rate of mobile phase is 1.5ml/min；With the phosphate-buffered salt (phosphoric acid of 0.01mol/L
Dihydro sodium solution sets 6.8~7.0 with the sodium hydroxide tune pH of 1mol/L)-acetonitrile (1000:53) be mobile phase A, with methanol be stream
Dynamic phase B, gradient are as follows:
Experimental procedure
Take dolasetron mesilate injection that about dolasetron mesilate 6.25mg is made in every 1ml with 20% dilution in acetonitrile
Sample solution；It is made in every 1ml after taking dolasetron mesilate injection to destroy 5 hours in 150 DEG C with 20% dilution in acetonitrile
About dolasetron mesilate 6.25mg high temperature degradation sample solution.
100 μ l of sample solution and high temperature degradation sample solution is taken, liquid chromatograph is injected, is surveyed by the chromatographic condition
It is fixed, chromatogram is recorded, the measurement in relation to substance is completed；Fig. 1 is that the HPLC of sample solution schemes, and Fig. 2 is high temperature degradation sample
HPLC figure.
It can be seen that from testing result, the method for the present invention can effectively divide the related substance of dolasetron mesilate injection
From, by high temperature degradation make degradation impurity increase after, be still able to achieve efficiently separating for impurity, method specificity is good.
Comparative test 1 (dolasetron mesilate USP standard conditions)
Detecting instrument and chromatographic condition
Detecting instrument: Shimadzu LC-20AT high performance liquid chromatograph
Chromatographic condition: chromatographic column is ZORBAX SB C8 column (250 × 4.6mm), and chromatographic column column temperature is 25 DEG C, and use is ultraviolet
Detector, Detection wavelength are set as 210nm；Flow rate of mobile phase is 1.5ml/min；With the phosphate-buffered salt (phosphoric acid of 0.01mol/L
It is mobile phase A that two ammonium salt solution of hydrogen, which sets 7.0)-acetonitrile (1000:53) with the phosphoric acid tune pH of 2mol/L, with phosphate-buffered salt
(ammonium dibasic phosphate solution of 0.01mol/L sets 7.0 with the phosphoric acid tune pH of 2mol/L)-acetonitrile (295:795) is Mobile phase B, is washed
De- gradient are as follows:
Experimental procedure: it is made often after taking dolasetron mesilate injection to destroy 5 hours in 150 DEG C with 20% dilution in acetonitrile
About dolasetron mesilate 6.25mg high temperature degradation sample solution in 1ml；Separately take dolasetron mesilate injection with 20% second
The about sample solution of dolasetron mesilate 6.25mg is made in every 1ml in nitrile dilution.
100 μ l of high temperature degradation sample solution is taken, liquid chromatograph is injected, is measured by the chromatographic condition, chromatography is recorded
Figure, completes the measurement in relation to substance；Fig. 3 is sample HPLC figure under this condition, and Fig. 4 is high temperature degradation sample under this condition
HPLC figure.
It can be seen that from testing result, the impurity before and after main peak is not implemented and efficiently separates, and cannot reach separation requirement, USP
Chromatographic condition used in raw material is the separation in relation to substance that can not achieve injection in standard.
Comparative test 2
Detecting instrument and chromatographic condition
Detecting instrument: Shimadzu LC-20AT high performance liquid chromatograph
Chromatographic condition: chromatographic column is ZORBAX SB C8 column (250 × 4.6mm), and chromatographic column column temperature is 25 DEG C, and use is ultraviolet
Detector, Detection wavelength are set as 210nm；Flow rate of mobile phase is 1.5ml/min；With the phosphate-buffered salt (phosphoric acid of 0.01mol/L
Dihydro sodium solution sets 6.8~7.0 with the sodium hydroxide tune pH of 1mol/L)-acetonitrile (1000:53) be mobile phase A, with methanol be stream
Dynamic phase B, gradient are as follows:
Experimental procedure: 1 method compounding system solution of comparative experiments is pressed.
100 μ l of high temperature degradation sample solution is taken, liquid chromatograph is injected, is measured by the chromatographic condition, chromatography is recorded
Figure, completes the measurement in relation to substance；Fig. 5 is high temperature degradation sample HPLC figure under this condition.
It can be seen that from testing result, the impurity after main peak realizes baseline separation, but the impurity before main peak is not implemented effective
Separation, cannot reach separation requirement.
Comparative test 3
Detecting instrument and chromatographic condition
Detecting instrument: Shimadzu LC-20AT high performance liquid chromatograph
Chromatographic condition: chromatographic column is ZORBAX SB C8 column (250 × 4.6mm), and chromatographic column column temperature is 25 DEG C, and use is ultraviolet
Detector, Detection wavelength are set as 210nm；Flow rate of mobile phase is 1.5ml/min；With the phosphate-buffered salt (phosphoric acid of 0.01mol/L
Dihydro sodium solution sets 6.8~7.0 with the sodium hydroxide tune pH of 1mol/L)-acetonitrile (1000:53) be mobile phase A, with methanol be stream
Dynamic phase B, gradient are as follows:
Time (min) A (%) B (%)
0 75 25
90 10 95
Experimental procedure: 1 method compounding system solution of comparative experiments is pressed.
100 μ l of high temperature degradation sample solution is taken, liquid chromatograph is injected, is measured by the chromatographic condition, chromatography is recorded
Figure, completes the measurement in relation to substance；Fig. 6 is high temperature degradation sample HPLC figure under this condition.
It can be seen that from testing result, the impurity before main peak realizes baseline separation, but the impurity after main peak is not implemented effective
Separation, cannot reach separation requirement.
Comparative test 4
Detecting instrument and chromatographic condition
Detecting instrument: Shimadzu LC-20AT high performance liquid chromatograph
Chromatographic condition: chromatographic column is ZORBAX SB C8 column (250 × 4.6mm), and chromatographic column column temperature is 25 DEG C, and use is ultraviolet
Detector, Detection wavelength are set as 210nm；Flow rate of mobile phase is 1.5ml/min；With the phosphate-buffered salt (phosphoric acid of 0.01mol/L
Dihydro sodium solution sets 6.8~7.0 with the sodium hydroxide tune pH of 1mol/L)-acetonitrile (1000:53) be mobile phase A, with methanol be stream
Dynamic phase B, gradient are as follows:
Experimental procedure: 1 method compounding system solution of comparative experiments is pressed.
100 μ l of high temperature degradation sample solution is taken, liquid chromatograph is injected, is measured by the chromatographic condition, chromatography is recorded
Figure, completes the measurement in relation to substance；Fig. 7 is high temperature degradation sample HPLC figure under this condition.
It can be seen that from testing result, the impurity after main peak realizes that the impurity before baseline separation but main peak appoints that there are two not substantially
Realization efficiently separates, and cannot reach separation requirement.
By comparative study as it can be seen that detection method specificity of the invention is good, testing requirements can be reached, in detectable concentration
Under effectively the related substance of dolasetron mesilate injection can be detected.So the present invention is used for dolasetron mesilate
The related substance detection of injection is an effective method.
Simultaneously, it is noted that it will be apparent to one skilled in the art that, without departing from the principle of the present invention,
Several improvement and polishing can be still made, these are improved and polishing also should be regarded as protection scope of the present invention.
Claims (10)
1. a kind of detection method of the dolasetron mesilate injection in relation to substance, this method is high performance liquid chromatography, special
Sign is, chromatographic condition are as follows: using the filler of Silica Surface bonding C8 functional group as chromatographic column fixed phase；With pH for 6.5~7.5
Buffer-acetonitrile be mobile phase A, it is stream with methanol that the volume ratio of buffer and acetonitrile, which is (900~1100): (50~56),
Dynamic phase B, is carried out according to the following table gradient elution:
2. detection method of the dolasetron mesilate injection in relation to substance according to claim 1, which is characterized in that press
Gradient elution is carried out according to following table:
3. detection method of the dolasetron mesilate injection in relation to substance according to claim 1, which is characterized in that institute
Stating buffer is phosphate or acetate buffer.
4. detection method of the dolasetron mesilate injection in relation to substance according to claim 1, which is characterized in that institute
Stating pH of buffer is 6.8~7.0.
5. detection method of the dolasetron mesilate injection in relation to substance according to claim 3, which is characterized in that institute
Stating phosphate is sodium dihydrogen phosphate or diammonium hydrogen phosphate.
6. detection method of the dolasetron mesilate injection in relation to substance according to claim 5, which is characterized in that institute
The gained of sodium hydroxide solution tune pH to 6.5~7.5 that buffer is the sodium dihydrogen phosphate 1mol/L of 0.01mol/L is stated,
The volume ratio of buffer and acetonitrile is 1000:53.
7. detection method of the dolasetron mesilate injection in relation to substance according to claim 1, which is characterized in that should
Method uses UV detector, and Detection wavelength is 200nm~220nm；Flow rate of mobile phase is 1.0ml/min~2.0ml/min；Color
Composing column column temperature is 20 DEG C~30 DEG C.
8. detection method of the dolasetron mesilate injection in relation to substance according to claim 1, which is characterized in that institute
Stating flow rate of mobile phase is 1.5ml/min.
9. detection method of the dolasetron mesilate injection in relation to substance according to claim 1, which is characterized in that institute
Stating Detection wavelength is 210nm.
10. detection method of the dolasetron mesilate injection in relation to substance according to claim 1, which is characterized in that
The following steps are included:
A) takes dolasetron mesilate injection that about dolasetron mesilate 6.25mg is made in every 1ml with 20% dilution in acetonitrile
Sample solution；
B) about methylsulphur is made in every 1ml with 20% dilution in acetonitrile after takes 150 DEG C of dolasetron mesilate injection destructions 5 hours
Sour Dolasetron 6.25mg high temperature degradation solution；
C) takes 100 μ l of solution a), b), injects liquid chromatograph, measures by the chromatographic condition, records chromatogram, completes
Measurement in relation to substance.
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| CN107703227B (en) * | 2017-10-17 | 2020-11-13 | 成都新恒创药业有限公司 | High performance liquid chromatography detection method for dolasetron mesylate chiral isomer |
| CN108732263B (en) * | 2018-04-03 | 2021-04-09 | 上海旭东海普药业有限公司 | Method for determining impurities in ramosetron hydrochloride injection |
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| CN102183589B (en) * | 2010-07-02 | 2013-04-24 | 成都新恒创药业有限公司 | Method for detecting contents of dolasetron isomer and salt thereof |
| CN103006547A (en) * | 2011-09-28 | 2013-04-03 | 辽宁海思科制药有限公司 | Dolasetron mesylate containing injection, as well as preparation method and quality control method thereof |
| CN103040721B (en) * | 2012-12-17 | 2014-07-02 | 海南圣欣医药科技有限公司 | Dolasetron mesylate lipidosome injection |
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