CN108872406A - HPLC analyzing detecting method in relation to substance in a kind of L-aminobutanedioic acid bulk pharmaceutical chemicals - Google Patents
HPLC analyzing detecting method in relation to substance in a kind of L-aminobutanedioic acid bulk pharmaceutical chemicals Download PDFInfo
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- aminobutanedioic
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- 239000000126 substance Substances 0.000 title claims abstract description 94
- 238000000034 method Methods 0.000 title claims abstract description 36
- 238000004128 high performance liquid chromatography Methods 0.000 title claims abstract description 13
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims abstract description 32
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000001514 detection method Methods 0.000 claims abstract description 25
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims abstract description 18
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000007859 condensation product Substances 0.000 claims abstract description 18
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000001630 malic acid Substances 0.000 claims abstract description 17
- 235000011090 malic acid Nutrition 0.000 claims abstract description 17
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 16
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 16
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims abstract description 16
- 239000001530 fumaric acid Substances 0.000 claims abstract description 16
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims abstract description 16
- 239000011976 maleic acid Substances 0.000 claims abstract description 16
- 239000011975 tartaric acid Substances 0.000 claims abstract description 16
- 235000002906 tartaric acid Nutrition 0.000 claims abstract description 16
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 14
- 239000007853 buffer solution Substances 0.000 claims abstract description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 58
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 23
- 239000013558 reference substance Substances 0.000 claims description 20
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 12
- 239000012490 blank solution Substances 0.000 claims description 11
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 238000010812 external standard method Methods 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 238000005070 sampling Methods 0.000 claims 1
- 230000003595 spectral effect Effects 0.000 claims 1
- 208000011117 substance-related disease Diseases 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 49
- 238000004458 analytical method Methods 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 10
- 238000000926 separation method Methods 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 7
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 230000002349 favourable effect Effects 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000012360 testing method Methods 0.000 description 19
- 239000012085 test solution Substances 0.000 description 13
- 239000012071 phase Substances 0.000 description 9
- 238000011084 recovery Methods 0.000 description 9
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 239000012266 salt solution Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- 230000003252 repetitive effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- UXAMZEYKWGPDBI-UHFFFAOYSA-N C(CCCCCCCCCCCCCCC)Br(C)(C)C Chemical compound C(CCCCCCCCCCCCCCC)Br(C)(C)C UXAMZEYKWGPDBI-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010020575 Hyperammonaemia Diseases 0.000 description 1
- 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 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- AJSHDAOMUKXVDC-UHFFFAOYSA-N butan-1-amine;sulfuric acid Chemical compound CCCC[NH3+].OS([O-])(=O)=O AJSHDAOMUKXVDC-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 1
- 229960002422 lomefloxacin Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- IZGYIFFQBZWOLJ-CKAACLRMSA-N phaseic acid Chemical compound C1C(=O)C[C@@]2(C)OC[C@]1(C)[C@@]2(O)C=CC(/C)=C\C(O)=O IZGYIFFQBZWOLJ-CKAACLRMSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
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)
- Spectroscopy & Molecular Physics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to technical field of analytical chemistry, specifically disclose the HPLC analyzing detecting method in relation to substance in a kind of L-aminobutanedioic acid bulk pharmaceutical chemicals, more specifically, a kind of method of L-aminobutanedioic acid, tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid and L-aminobutanedioic acid condensation product or the drug containing above-mentioned 7 kinds of substances in analysis detection L-aminobutanedioic acid raw material is disclosed.The application is optimized by conditions such as selection, the solution ph of composition, ion-pairing agent to buffer solution, take into account the needs of L-aminobutanedioic acid and 6 related substance separation in L-aminobutanedioic acid bulk pharmaceutical chemicals, finally establish analysis method appropriate, analytical cycle is controlled in 40min, between principal component and each related substance, it can reach baseline separation between each related substance, specificity is good, favorable reproducibility, accuracy is high, precision is high.
Description
Technical field
The present invention relates to technical field of analytical chemistry, and in particular to the HPLC in relation to substance in a kind of L-aminobutanedioic acid bulk pharmaceutical chemicals
Analyzing detecting method, more specifically to L-aminobutanedioic acid in a kind of analysis detection L-aminobutanedioic acid raw material, tartaric acid, malic acid,
The method of maleic acid, succinic acid, fumaric acid and L-aminobutanedioic acid condensation product or the drug containing above-mentioned 7 kinds of substances.
Background technique
Closely related in relation to substance and drug quality, safety and curative effect, the presence in relation to substance may reduce drug
Curative effect, or even cause toxic side effect, therefore, it is necessary to pass through the kind that determination method appropriate controls Drug-related
Class and content, it is ensured that drug quality.
L-aminobutanedioic acid is one of 18 kinds of necessary amino acid of human body, and utilization can be fully absorbed by human body, improves human immunity
Power can be used as nutritional supplement use；Due in molecule contain two carboxyls and an amino, belong to acidic amino acid, can with sodium,
Potassium, calcium, magnesium, ornithine are widely used in various hepatitis, cirrhosis, hyperammonemia or heart disease as amino acids drug at salt
Treatment, can also can more promote the activity of substance at salt with Lomefloxacin, Amlodipine, azithromycin etc..
There may be six kinds of related substances, respectively tartaric acid, malic acid, horse in process of production for L-aminobutanedioic acid bulk pharmaceutical chemicals
Come sour, succinic acid, fumaric acid and L-aminobutanedioic acid condensation product.The number of above-mentioned 6 kinds of related substances, content directly affects a winter
The quality of propylhomoserin or derivatives thereof easily causes the adverse reaction of human body and generates medicine irritation.Chinese Pharmacopoeia, United States Pharmacopeia
Limit test is carried out only with thin-layered chromatography with L-aminobutanedioic acid Related substances separation method in British Pharmacopoeia, can not specifically be determined
Measure the content in relation to substance；Separation can accurately also be detected using same chromatographic condition without clearly report in existing document
6 kinds of methods in relation to substance.
Summary of the invention
For the deficiencies in the prior art, the technical problem to be solved by the present invention is to how construct a kind of chromatostrip
Part can simultaneously accurately above-mentioned 6 kinds of related substances in analysis detection L-aminobutanedioic acid bulk pharmaceutical chemicals, each related structure of matter formula difference
It is as follows：
Present inventor by the conditions such as selection, the solution ph of composition, ion-pairing agent to buffer solution into
Row screening takes into account the needs of L-aminobutanedioic acid and 6 related substance separation in L-aminobutanedioic acid bulk pharmaceutical chemicals, finally establishes appropriate point
Analytical cycle control can be reached base between 40min, principal component and each related substance, between each related substance by analysis method
Line separation, reaches the purpose of the present invention.
Technical solution provided by the invention is：
A kind of analyzing detecting method of the L-aminobutanedioic acid in relation to substance, includes the following steps：
A. L-aminobutanedioic acid bulk pharmaceutical chemicals are taken, with the aqueous solution of water, mobile phase, phosphoric acid solution or organic solvent, are configured to containing door
The solution of 1~10mg/ml of aspartic acid, preferably 4mg/ml；
The aqueous solution of the organic solvent is selected from the aqueous solution of alcohols or nitrile, preferably methanol or acetonitrile solution.
It is preferred that being dissolved with mobile phase or phosphoric acid solution, the phosphoric acid solution concentration is 0.0085wt%~0.85wt%, most
It is preferred that 0.085wt%.
B. it takes step a acquired solution appropriate, is injected into high performance liquid chromatograph, is rinsed with mobile phase, the height
Performance liquid chromatographic column in effect liquid phase chromatogram instrument is using octadecylsilane chemically bonded silica as packed column, the chromatography of preferred hydrophilic
Column, column temperature can be 20~60 DEG C, and chromatographic column is Inetsil ODS-SP, 4.6 × 250mm, 5 μm, column in some embodiments
30 DEG C of temperature.
C. the ultraviolet light detection of 200~220nm of wavelength, best detection wavelength 205nm are used.
D. flow rate of mobile phase can be 0.1~1ml/min, preferably 0.2~0.8ml/min, most preferably 0.3~
0.5ml/min。
One or more of containing following six kinds of related substances in the L-aminobutanedioic acid bulk pharmaceutical chemicals, preferably five kinds or
Six kinds：Tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid and L-aminobutanedioic acid condensation product.
The mobile phase is made of the inorganic mixed salt solution of amine-ion-pairing agent-and chromatographically pure organic solvent, the amine
The volume ratio of the inorganic mixed salt solution of class-ion-pairing agent-and organic solvent is 99:1~85:15, preferably 98:2~88:
12, most preferably 96:4~90:10.
The inorganic mixed salt solution of amine-ion-pairing agent-can be understood as buffer solution.
The preferred methanol of the chromatographically pure organic solvent or acetonitrile, optimal is methanol.
The pH value of the inorganic mixed salt solution of amine-ion-pairing agent-is 4.5~5.5, preferably 4.8~5.2.It is described
In the inorganic mixed salt solution of amine-ion-pairing agent-containing amine 0.05%~0.2% (V/V), containing inorganic salts 0.01~
0.05mol/L, 0.001~0.015mol/L containing ion-pairing agent, in the inorganic mixed salt solution of amine-ion-pairing agent-
Also containing the inorganic acid for adjusting pH value.
The preferred diethylamine of the amine, triethylamine, optimal is triethylamine.
The preferred potassium dihydrogen phosphate of the inorganic salts, sodium dihydrogen phosphate, dipotassium hydrogen phosphate and/or disodium hydrogen phosphate, most preferably
Potassium dihydrogen phosphate.
The preferred tetrabutylammonium hydroxide of the ion-pairing agent, 4-butyl ammonium hydrogen sulfate and/or cetyl trimethyl bromine
Change ammonium, most preferably tetrabutylammonium hydroxide.
The preferred phosphoric acid of the inorganic acid and/or trifluoroacetic acid, preferably phosphoric acid.
Method of the present invention using the related substance in HPLC separation determination L-aminobutanedioic acid bulk pharmaceutical chemicals, it is characterized in that
Chromatographic condition is as follows：
Chromatographic column：Inetsil ODS-SP, 4.6 × 250mm, 5 μm；
Detector：UV detector, Detection wavelength 205nm；
Flow velocity：0.3~0.5ml/min；
Column temperature：20~60 DEG C；
Mobile phase：Buffer solution (0.01~0.05mol of phosphoric acid potassium dihydrogen in every 1000ml buffer solution, contains the tetrabutyl
0.001~0.015mol of ammonium hydroxide, 0.5~2ml containing triethylamine are 4.8~5.2 with phosphoric acid tune pH value)-methanol (96:4~
90:10)；
The process for preparation of the buffer is：0.01~0.05mol of potassium dihydrogen phosphate and tetrabutyl hydrogen-oxygen is added in Xiang Shuizhong
Change 0.001~0.015mol of ammonium, adds 0.5~2ml of triethylamine, then add water to liquor capacity close to 1000ml, then use phosphorus
It is 4.8~5.2 that acid, which adjusts pH value, finally adds water to 1000ml.
Test solution is：The solution of every 1ml about 4mg containing L-aminobutanedioic acid is made of the dissolution of 0.085wt% phosphoric acid；Sample introduction body
Product is 50 μ l.
The method of related substance of the present invention with HPLC separation determination L-aminobutanedioic acid bulk pharmaceutical chemicals, can use to have
Close the related content of material in substance peak area external standard method calculating L-aminobutanedioic acid bulk pharmaceutical chemicals.
Compared with prior art, the advantages of the present invention are as follows：
Specificity is good, favorable reproducibility, accuracy is high, precision is high.
Detailed description of the invention
Fig. 1 is the chromatogram of the blank solution of 1 specificity of embodiment test；
Fig. 2 is the chromatogram of the system suitability solution of 1 specificity of embodiment test；
Fig. 3 is the chromatogram for the related substance reference substance solution that specificity is tested in embodiment 1；
Fig. 4 is the chromatogram for the test solution that specificity is tested in embodiment 1.
Specific embodiment
In order to make those skilled in the art understand that the content of present invention, below applicant will further retouch in conjunction with specific embodiments
Technical solution of the present invention is stated, but the following contents is not limit the invention in any way.
Reagent used in the present invention is available on the market or can described method system through the invention
It is standby and obtain.Wherein L-aminobutanedioic acid bulk pharmaceutical chemicals come from Nanning Ying Chuanmei poem pharmaceutcal corporation, Ltd, and lot number is：8811650901, content
It is 100.3%.
The reagent used in analysis method provided by the present invention is to meet Chinese Pharmacopoeia 2015 editions analytical reagents to want
It asks.
The test of 1 specificity of embodiment
Chromatographic condition：
Instrument：Waters high performance liquid chromatograph 2695；
Chromatographic column：Inetsil ODS-SP, 4.6 × 250mm, 5 μm；
Detector：UV detector, Detection wavelength 205nm；
Flow velocity：0.4ml/min；
Column temperature：30℃；
Mobile phase：Buffer solution (phosphoric acid potassium dihydrogen 0.01mol, tetrabutylammonium hydroxide in every 1000ml buffer solution
Ammonium 0.008mol, triethylamine 1.2ml are that (buffer solution and methanol volume ratio are 94 to 5.0)-methanol with phosphoric acid tune pH value:6)；
Test procedure：
Dilution (blank solution)：0.085wt% phosphoric acid.
System suitability solution：Accurately weigh L-aminobutanedioic acid bulk pharmaceutical chemicals and tartaric acid, malic acid, maleic acid, succinic acid, richness
Horse acid, each reference substance of L-aminobutanedioic acid condensation product are appropriate, set in same volumetric flask, 0.085wt% phosphoric acid solution is added to make to dissolve in right amount
And it dilutes and is made in every 1ml containing about L-aminobutanedioic acid 4mg, tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid and L-aminobutanedioic acid
The solution of each 10 μ g of condensation product, as system suitability solution.
Related substance reference substance solution：Precision weighs tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid, door winter ammonia
Sour each reference substance of condensation product is appropriate, sets in same volumetric flask, adds 0.085wt% phosphoric acid solution to dissolve and quantifies dilution and is made often
Containing each mixed solution in relation to about 4 μ g of substance reference substance in 1ml, as related substance reference substance solution.
Test solution：L-aminobutanedioic acid bulk pharmaceutical chemicals about 0.4g is taken, it is accurately weighed, it sets in 100ml measuring bottle, adds 0.085wt%
Phosphoric acid solution makes to dissolve and be diluted to scale, shakes up, as test solution.
It is accurate respectively to measure blank solution, system suitability solution, test solution, related substance reference substance solution each 50
μ l records chromatogram using above-mentioned chromatographic condition sample detection.Blank map such as Fig. 1, system suitability solution map such as Fig. 2,
Reference substance solution map such as Fig. 3, test solution map such as Fig. 4.It is former that L-aminobutanedioic acid is calculated by related substance peak area external standard method
Expect the content in relation to substance in medicine.Testing result is as shown in table 1.
Table 1
2 serviceability test of embodiment
The present embodiment investigates the durability of chromatographic process by the parameter of changing section chromatographic condition, with following chromatographic condition
Based on：
Chromatographic condition：
Instrument：Waters high performance liquid chromatograph 2695；
Chromatographic column：Inetsil ODS-SP, 4.6 × 250mm, 5 μm；
Detector：UV detector, Detection wavelength 205nm；
Flow velocity：0.4ml/min；
Column temperature：30℃；
Mobile phase：Buffer solution (phosphoric acid potassium dihydrogen 0.01mol in every 1000ml, tetrabutylammonium hydroxide 0.008mol,
Triethylamine 1.2ml is 5.0)-methanol (volume ratio 94 with phosphoric acid tune pH value:6)；
Test procedure：
It is investigated in a manner of single factor test variation and changes flow velocity, chromatogram column temperature, the different Inetsil for producing series of replacement
ODS-SP, 4.6 × 250mm, the chromatographic conditions such as 5 μm of chromatographic columns or the ratio for flowing phase composition are to detection system applicability solution
It influences, main investigate changes chromatographic condition to the influence in relation to the separating degree substance each in system suitability solution.
Dilution (blank solution)：0.085wt% phosphoric acid.
System suitability solution：Accurately weigh L-aminobutanedioic acid bulk pharmaceutical chemicals, tartaric acid, malic acid, maleic acid, succinic acid, richness
Horse acid, each reference substance of L-aminobutanedioic acid condensation product are appropriate, set in same volumetric flask, 0.085wt% phosphoric acid solution is added to make to dissolve in right amount
And it dilutes and is made in every 1ml containing about L-aminobutanedioic acid 4mg, tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid and L-aminobutanedioic acid
The solution of each 10 μ g of condensation product, as system suitability solution.
It is accurate respectively to measure 50 μ l of system suitability solution under each investigation chromatographic condition, record each chromatogram.Separating degree
Testing result is as shown in table 2.
Table 2
3 Precision Experiment of embodiment
Chromatographic condition is chromatographic condition as described in Example 1.
Dilution (blank solution)：0.085wt% phosphoric acid.
Related substance reference substance solution：Precision weighs tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid, door respectively
Each reference substance of aspartic acid condensation product is appropriate, sets in same volumetric flask, adds 0.085wt% phosphoric acid solution to dissolve and quantifies dilution and is made
Mixed solution containing each about 4 μ g of reference substance in every 1ml, as related substance reference substance solution.
Repetitive test solution：L-aminobutanedioic acid bulk pharmaceutical chemicals about 0.4g is taken, it is accurately weighed, it sets in 100ml volumetric flask, adds
0.085wt% phosphoric acid solution makes to dissolve and be diluted to scale, shakes up.It is parallel to prepare 6 parts.
It is accurate respectively to measure blank solution, repetitive test solution, related each 50 μ l of substance reference substance solution, using implementation
Chromatographic condition sample detection described in example 1 records chromatogram.It is molten that 6 parts of repetitive tests are calculated by related substance peak area external standard method
Content, calculating relative standard deviation value (RSD) in liquid in relation to substance, testing result is as shown in table 3.
Table 3
4 recovery test of embodiment
Chromatographic condition is chromatographic condition as described in Example 1.
Dilution (blank solution)：0.085wt% phosphoric acid.
It is prepared in relation to substance reference substance solution by the preparation method in embodiment 1.
Test solution is prepared by the preparation method in embodiment 1.
Preparation in relation to substance mother liquor：Precision weighs tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid, door winter ammonia
Sour condensation product reference substance is each appropriate, sets in same volumetric flask, adds 0.085wt% phosphoric acid solution to dissolve and quantifies dilution and is made often
Mixed solution containing each about 20 μ g of reference substance in 1ml, as mixing related substance mother liquor.
Recovery test solution：L-aminobutanedioic acid bulk pharmaceutical chemicals 100mg is taken, it is accurately weighed, it sets in the volumetric flask of 25ml, it is parallel to claim
Take 9 parts, number 1-9 is spare.Precision measures related tri- parts of substance mother liquor 4ml and is set in above-mentioned 1-3 25ml volumetric flask respectively,
Scale is dissolved and be diluted to 0.085wt% phosphoric acid solution, is shaken up, as 80%-1,80%-2 and 80%-3 rate of recovery solution；
Precision measures related tri- parts of substance mother liquor 5ml and is set in above-mentioned 4-6 25ml volumetric flask respectively, molten with 0.085wt% phosphoric acid solution
Scale is solved and be diluted to, is shaken up, as 100%-1,100%-2 and 100%-3 rate of recovery solution；It is female that precision measures related substance
Tri- parts of liquid 6ml are set respectively in above-mentioned 7-9 volumetric flask, and scale is dissolved and be diluted to 0.085wt% phosphoric acid solution, is shaken up, and are made
For 120%-1,120%-2 and 120%-3 rate of recovery solution.
It is accurate respectively to measure blank solution, related substance reference substance solution, test solution, recovery test solution each 50
μ l records chromatogram using chromatographic condition sample detection described in embodiment 1.9 parts are calculated by related substance peak area external standard method to return
Each content in relation to substance in yield testing liquid, using the ratio of measured amount and the amount of being actually added into as the rate of recovery, testing result is shown in
Shown in table 4.
Table 4
5 linear test of embodiment
Precision measure embodiment 4 under related substance mother liquor 2.0ml, 3.0ml, 4.0ml, 5.0ml, 6.0ml, 7.0ml,
8.0ml is set respectively in 25ml volumetric flask, is diluted to scale with 0.085wt% phosphoric acid solution, is shaken up, as linear solvent, respectively
Precision measures each 50 μ l of linear solvent, using chromatographic condition sample detection described in embodiment 1, records chromatogram.By peak area and
Concentration calculation linear equation, and related coefficient is calculated, each related substance linearly the results are shown in Table shown in 5.
Table 5
Each related substance detection limit measurement of embodiment 6
According to signal-to-noise ratio method, tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid, L-aminobutanedioic acid condensation product are taken respectively
Reference substance is each appropriate, and the test solution of various concentration is respectively prepared with 0.085wt% phosphoric acid solution；Using described in embodiment 1
Chromatographic condition sample detection records chromatogram, when being 3 times of instrument noise signal in relation to material absorbing peak-to-peak signal, as inspection
Limit is surveyed, when being 10 times of instrument noise signal in relation to material absorbing peak-to-peak signal, as quantitative limit, through testing, it is determined that respectively have
The quantitative limit for closing the detection limit of substance, the results are shown in Table 6.
Table 6
| Related substance title | Quantitative limit | Detection limit |
| L-aminobutanedioic acid condensation product | 38.437ng | 11.531ng |
| Succinic acid | 200.97ng | 60.291ng |
| Malic acid | 195.85ng | 59.655ng |
| Tartaric acid | 203.975ng | 61.193ng |
| Maleic acid | 3.980ng | 1.194ng |
| Fumaric acid | 4.095ng | 1.229ng |
In conclusion the experimental result and map 1-4 of embodiment 1 show method provided by the invention in detection door winter ammonia
The related substance of acid starting material medicine, especially detection tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid, L-aminobutanedioic acid condensation product
When, blank is noiseless, has a good specificity, and main peak and each separating degree in relation to substance peak are 39.0 or more, each related object
Separating degree between matter is 1.8 or more.
Embodiment 2 the experimental results showed that in the case where single factor test changing section chromatographic condition parameter, this method is still
Suitable for the related substance of detection L-aminobutanedioic acid bulk pharmaceutical chemicals, wherein the separating degree for the system suitability solution investigated is impacted less,
The method has good durability, and change chromatographic condition in the appropriate range does not influence this method realization analysis mesh completely
's.
Embodiment 3 the experimental results showed that using analysis method provided by the invention measurement L-aminobutanedioic acid raw material in it is related
Substance repeats detection 6 times, and each related content of material measurement result relative standard deviation is below 3.0%.
The test result of embodiment 4 by the tartaric acid of various concentration level in measurement bulk pharmaceutical chemicals, malic acid, maleic acid,
The rate of recovery of succinic acid, fumaric acid, L-aminobutanedioic acid condensation product investigates analysis method of the invention in measurement in relation to the accurate of substance
Property.The experimental results showed that each related substance average recovery rate of various concentration level is 98% or more, each related substance is recycled
The relative standard deviation of rate is below 2.5%.Therefore the method has in the related substance of measurement L-aminobutanedioic acid bulk pharmaceutical chemicals
Good accuracy.
The test result of embodiment 5 shows each related substance linear regression coeffficient r in the range of about 1~8 μ g/mL2?
Greater than 0.99, it was confirmed that good linear relationship.
The test result of embodiment 6 shows that analysis method provided by the invention has higher spirit to each detection in relation to substance
Sensitivity.
Therefore, analysis method provided by the present invention related substance in measurement L-aminobutanedioic acid bulk pharmaceutical chemicals has specificity
Good, favorable reproducibility, the advantages that accuracy is high, precision is high.
Method of the invention is described by preferred embodiment, related personnel obviously can the content of present invention,
To method described herein and application is modified or appropriate changes and combinations in spirit and scope, carry out the implementation and application present invention
Technology.Those skilled in the art can use for reference present disclosure, be suitably modified realization of process parameters.In particular, it should be pointed out that institute
There are similar replacement and change will be apparent to persons skilled in the art, they will all be deemed to be included in the present invention and ask
In the range of asking protection.
Claims (7)
1. the HPLC analyzing detecting method in a kind of L-aminobutanedioic acid bulk pharmaceutical chemicals in relation to substance, it is characterised in that：The related substance
Including one or more of tartaric acid, malic acid, maleic acid, succinic acid, fumaric acid and L-aminobutanedioic acid condensation product；It is described
The chromatographic condition of HPLC analyzing detecting method is as follows：
Chromatographic column：Hydrophilic octadecylsilane chemically bonded silica chromatography column；
Detector：UV detector, 200 ~ 220nm of Detection wavelength；
Column temperature：20~60℃；
Mobile phase：Buffer solution-methanol, buffer solution and methanol volume ratio are 96:4~90:10；
Flow rate of mobile phase：0.1~1ml/min；
0.01 ~ 0.05mol of phosphoric acid potassium dihydrogen, tetrabutylammonium hydroxide 0.001 in buffer solution described in every 1000ml ~
0.015mol, 0.5 ~ 2ml of triethylamine are 4.8 ~ 5.2 with phosphoric acid tune pH value.
2. HPLC analyzing detecting method according to claim 1, it is characterised in that：The color of the HPLC analyzing detecting method
Spectral condition is as follows：
Chromatographic column：Inetsil ODS-SP, 4.6 × 250mm, 5 μm；
Detector：UV detector, Detection wavelength 205nm；
Column temperature：28-32℃；
Mobile phase：Buffer solution-methanol, buffer solution and methanol volume ratio are 96:4~92:8；
Flow velocity：0.3-0.5ml/min；
Phosphoric acid potassium dihydrogen 0.01mol, tetrabutylammonium hydroxide 0.008mol, triethylamine in buffer solution described in every 1000ml
1.2ml is 5.0 with phosphoric acid tune pH value.
3. HPLC analyzing detecting method according to claim 1 or 2, it is characterised in that：The related substance includes apple
Acid, fumaric acid and L-aminobutanedioic acid condensation product.
4. HPLC analyzing detecting method according to claim 1 or 2, it is characterised in that：The related substance includes winestone
Five kinds in acid, malic acid, maleic acid, succinic acid, fumaric acid and L-aminobutanedioic acid condensation product or six kinds.
5. utilizing related object in the detection L-aminobutanedioic acid bulk pharmaceutical chemicals of HPLC analyzing detecting method described in claims 1 or 22 or 3 or 4
The method of matter, it is characterised in that：Each related substance is detected using peak area quantified by external standard method；
Sample to be tested and reference substance use sample introduction after blank solution dissolution process, the blank solution be 0.0085wt% ~
The phosphoric acid of 0.85wt%.
6. according to the method described in claim 5, it is characterized in that：The blank solution is the phosphoric acid of 0.085wt%.
7. according to the method described in claim 5, it is characterized in that：Sampling volume is 50 μ l.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112433011A (en) * | 2020-11-11 | 2021-03-02 | 南京逐陆医药科技有限公司 | Method for determining related substances in potassium magnesium aspartate xylitol injection |
| CN115524407A (en) * | 2021-06-25 | 2022-12-27 | 武汉武药科技有限公司 | Separation and detection method of organic acid |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2350802A (en) * | 1999-06-08 | 2000-12-13 | Anglia Polytechnic University | Sample pre-treatment |
| CN102288687A (en) * | 2010-06-21 | 2011-12-21 | 武汉启瑞药业有限公司 | Method for analysing and detecting impurities in ornithine aspartate |
| CN104807924A (en) * | 2014-01-28 | 2015-07-29 | 黑龙江天行健医药科技开发有限公司 | Method for detecting specific impurities in ornithine aspartate raw material and preparation thereof |
-
2017
- 2017-05-11 CN CN201710331368.XA patent/CN108872406B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2350802A (en) * | 1999-06-08 | 2000-12-13 | Anglia Polytechnic University | Sample pre-treatment |
| CN102288687A (en) * | 2010-06-21 | 2011-12-21 | 武汉启瑞药业有限公司 | Method for analysing and detecting impurities in ornithine aspartate |
| CN104807924A (en) * | 2014-01-28 | 2015-07-29 | 黑龙江天行健医药科技开发有限公司 | Method for detecting specific impurities in ornithine aspartate raw material and preparation thereof |
Non-Patent Citations (7)
| Title |
|---|
| M.H.M.N. SENDEN等: "Analysis of major tomato xylem organic acids and PITC-derivatives of amino acids by RP-HPLC and UV detection", 《PLANT AND SOIL》 * |
| NORBERT SZOBOSZLAI等: "Determination of energy metabolites in cancer cells by porous graphitic carbon liquid chromatography electrospray ionization mass spectrometry for the assessment of energy metabolism", 《ANALYTICA CHIMICA ACTA》 * |
| ULRIKE HOLZGRABE等: "Control of impurities in l-aspartic acid and l-alanine by high-performance liquid chromatography coupled with a corona charged aerosol detector", 《JOURNAL OF CHROMATOGRAPHY A》 * |
| 于治国，宋粉云 主编: "《药物分析》", 30 September 2010, 中国医药科技出版社 * |
| 徐三能 等: "HPLC法测定门冬氨酸钾镁注射液中门冬氨酸的含量", 《安徽医药》 * |
| 许芬芳: "高效液相色谱法测定测定门冬氨酸鸟氨酸原料中S-3-氨基哌啶-2-酮、精氨酸和谷氨酸的含量", 《海峡药学》 * |
| 谭畅 等: "HPLC测定L-天门冬氨酸中的有关物质", 《华西药学杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112433011A (en) * | 2020-11-11 | 2021-03-02 | 南京逐陆医药科技有限公司 | Method for determining related substances in potassium magnesium aspartate xylitol injection |
| CN112433011B (en) * | 2020-11-11 | 2022-08-02 | 南京逐陆医药科技有限公司 | Method for determining related substances in potassium magnesium aspartate xylitol injection |
| CN115524407A (en) * | 2021-06-25 | 2022-12-27 | 武汉武药科技有限公司 | Separation and detection method of organic acid |
| CN115524407B (en) * | 2021-06-25 | 2024-10-29 | 武汉武药科技有限公司 | Separation detection method of organic acid |
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