IL175511A - Rosuvastatin degradation products - Google Patents
Rosuvastatin degradation productsInfo
- Publication number
- IL175511A IL175511A IL175511A IL17551106A IL175511A IL 175511 A IL175511 A IL 175511A IL 175511 A IL175511 A IL 175511A IL 17551106 A IL17551106 A IL 17551106A IL 175511 A IL175511 A IL 175511A
- Authority
- IL
- Israel
- Prior art keywords
- rosuvastatin
- lactone
- degradation product
- solution
- acetonitrile
- Prior art date
Links
- 229960000672 rosuvastatin Drugs 0.000 title claims abstract description 60
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 title claims abstract description 60
- 239000007857 degradation product Substances 0.000 title claims abstract description 43
- 239000003550 marker Substances 0.000 claims abstract description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 102
- 150000002596 lactones Chemical group 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 20
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 17
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 16
- 159000000007 calcium salts Chemical class 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 13
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 229960004796 rosuvastatin calcium Drugs 0.000 claims description 11
- 230000014759 maintenance of location Effects 0.000 claims description 10
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 9
- 239000011575 calcium Substances 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 8
- 229910052791 calcium Inorganic materials 0.000 claims description 8
- 238000004587 chromatography analysis Methods 0.000 claims description 8
- 230000001678 irradiating effect Effects 0.000 claims description 8
- 238000001704 evaporation Methods 0.000 claims description 7
- 238000004809 thin layer chromatography Methods 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 5
- SOEGVMSNJOCVHT-VEUZHWNKSA-N Rosuvastatin lactone Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC(N(C)S(C)(=O)=O)=NC=1C1=CC=C(F)C=C1 SOEGVMSNJOCVHT-VEUZHWNKSA-N 0.000 claims description 5
- 239000001110 calcium chloride Substances 0.000 claims description 5
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 239000000377 silicon dioxide Substances 0.000 claims description 5
- -1 alkaline earth metal salt Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims 2
- 238000011084 recovery Methods 0.000 claims 1
- 238000004458 analytical method Methods 0.000 abstract description 4
- 239000012535 impurity Substances 0.000 description 10
- 239000003480 eluent Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000004451 qualitative analysis Methods 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000008186 active pharmaceutical agent Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 235000011148 calcium chloride Nutrition 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 238000004445 quantitative analysis Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 2
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229960005110 cerivastatin Drugs 0.000 description 2
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940066901 crestor Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960003765 fluvastatin Drugs 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229960002965 pravastatin Drugs 0.000 description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
- IKAACYWAXDLDPM-UHFFFAOYSA-N 1,2,3,4,4a,5-hexahydronaphthalene Chemical group C1=CCC2CCCCC2=C1 IKAACYWAXDLDPM-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- FFRUQSUMDFNBLG-UHFFFAOYSA-N 2-(2,4,5-trichlorophenoxy)ethyl 2,2,2-trichloroacetate Chemical compound ClC1=CC(Cl)=C(OCCOC(=O)C(Cl)(Cl)Cl)C=C1Cl FFRUQSUMDFNBLG-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- FESAXEDIWWXCNG-UHFFFAOYSA-N diethyl(methoxy)borane Chemical compound CCB(CC)OC FESAXEDIWWXCNG-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000007905 drug manufacturing Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 238000001448 refractive index detection Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000000357 thermal conductivity detection Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52644903P | 2003-12-02 | 2003-12-02 | |
| PCT/US2004/040329 WO2005056534A1 (en) | 2003-12-02 | 2004-12-02 | Reference standard for characterization of rosuvastatin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL175511A0 IL175511A0 (en) | 2006-09-05 |
| IL175511A true IL175511A (en) | 2011-11-30 |
Family
ID=34676616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL175511A IL175511A (en) | 2003-12-02 | 2006-05-09 | Rosuvastatin degradation products |
Country Status (13)
| Country | Link |
|---|---|
| US (6) | US7244844B2 (https=) |
| EP (1) | EP1689723B1 (https=) |
| JP (1) | JP4733047B2 (https=) |
| KR (1) | KR100887264B1 (https=) |
| CN (1) | CN1894221B (https=) |
| AT (1) | ATE507209T1 (https=) |
| CA (1) | CA2546894C (https=) |
| DE (1) | DE602004032465D1 (https=) |
| ES (1) | ES2364143T3 (https=) |
| IL (1) | IL175511A (https=) |
| PT (1) | PT1689723E (https=) |
| TW (1) | TWI351958B (https=) |
| WO (1) | WO2005056534A1 (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0218781D0 (en) | 2002-08-13 | 2002-09-18 | Astrazeneca Ab | Chemical process |
| GB0312896D0 (en) | 2003-06-05 | 2003-07-09 | Astrazeneca Ab | Chemical process |
| GB0324791D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Chemical process |
| CN1894221B (zh) * | 2003-12-02 | 2012-08-08 | 特瓦制药工业有限公司 | 用于表征罗苏伐他汀的参照标准品 |
| US7851624B2 (en) | 2003-12-24 | 2010-12-14 | Teva Pharamaceutical Industries Ltd. | Triol form of rosuvastatin and synthesis of rosuvastatin |
| US7612203B2 (en) * | 2005-02-22 | 2009-11-03 | Teva Pharmaceutical Industries Ltd. | Rosuvastatin and salts thereof free of rosuvastatin alkylether and a process for the preparation thereof |
| WO2007071357A2 (en) * | 2005-12-20 | 2007-06-28 | Lek Pharmaceuticals D.D. | Pharmaceutical composition comprising (e) -7- [4- (4-fluorophenyl) -6-isopropyl-2- [methyl (methylsulfonyl) amino] pyrimidin-5 -yl- (3r, 5s) -3, 5-dihydr0xyhept-6-en0ic acid |
| JP5330225B2 (ja) * | 2007-03-13 | 2013-10-30 | テバ ファーマシューティカル インダストリーズ リミティド | トリオール型ロスバスタチン |
| EP2189456A1 (en) * | 2008-11-14 | 2010-05-26 | LEK Pharmaceuticals d.d. | New compounds prepared from omeprazole |
| TWI461410B (zh) | 2008-12-30 | 2014-11-21 | Arqule Inc | 經取代之５，６－二氫－６－苯基苯並〔f〕異喹啉－２－胺化合物類 |
| CN103454352B (zh) * | 2013-07-30 | 2015-07-15 | 广东先强药业有限公司 | 一种hplc法测定瑞舒伐他汀钙的含量及其有关物质的方法 |
| CN103776939A (zh) * | 2014-02-11 | 2014-05-07 | 润泽制药(苏州)有限公司 | 瑞舒伐他汀钙制剂有关物质的制备检测方法 |
| CN108398501A (zh) * | 2018-03-02 | 2018-08-14 | 海南通用三洋药业有限公司 | 一种检测瑞舒伐他汀钙有关物质的方法 |
| CN109020902B (zh) * | 2018-07-23 | 2020-06-02 | 唯智医药科技（北京）有限公司 | 一种瑞舒伐他汀钙杂质及其制备方法与用途 |
| CN114280181B (zh) * | 2021-12-23 | 2024-06-18 | 浙江海翔川南药业有限公司 | 一种瑞舒伐他汀中间体及其有关物质的检测方法 |
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| US37314A (en) * | 1863-01-06 | Improved composition for lemonade | ||
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| US4231938A (en) | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| US4444784A (en) | 1980-08-05 | 1984-04-24 | Merck & Co., Inc. | Antihypercholesterolemic compounds |
| DK149080C (da) | 1980-06-06 | 1986-07-28 | Sankyo Co | Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre |
| US4739073A (en) | 1983-11-04 | 1988-04-19 | Sandoz Pharmaceuticals Corp. | Intermediates in the synthesis of indole analogs of mevalonolactone and derivatives thereof |
| NO177005C (no) | 1988-01-20 | 1995-07-05 | Bayer Ag | Analogifremgangsmåte for fremstilling av substituerte pyridiner, samt mellomprodukter til bruk ved fremstillingen |
| US5177080A (en) | 1990-12-14 | 1993-01-05 | Bayer Aktiengesellschaft | Substituted pyridyl-dihydroxy-heptenoic acid and its salts |
| JP3233403B2 (ja) | 1991-06-19 | 2001-11-26 | 塩野義製薬株式会社 | 光学活性な中間体および該製造法 |
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| GB9626746D0 (en) | 1996-12-23 | 1997-02-12 | Knoll Ag | Process |
| GB9812413D0 (en) | 1998-06-10 | 1998-08-05 | Glaxo Group Ltd | Compound and its use |
| SI20070A (sl) | 1998-09-18 | 2000-04-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Nove soli inhibitorjev HMG-CoA reduktaze |
| GB9903472D0 (en) | 1999-02-17 | 1999-04-07 | Zeneca Ltd | Chemical process |
| GB0001621D0 (en) | 2000-01-26 | 2000-03-15 | Astrazeneca Ab | Pharmaceutical compositions |
| GB0003305D0 (en) | 2000-02-15 | 2000-04-05 | Zeneca Ltd | Pyrimidine derivatives |
| GB0028429D0 (en) | 2000-11-22 | 2001-01-10 | Astrazeneca Ab | Therapy |
| KR20040026705A (ko) | 2001-08-16 | 2004-03-31 | 테바 파마슈티컬 인더스트리즈 리미티드 | 스타틴의 칼슘 염 형태의 제조 방법 |
| AU2002324715B2 (en) * | 2001-08-16 | 2009-03-12 | Teva Pharmaceutical Industries Ltd. | Processes for preparing calcium salt forms of statins |
| SE0103509D0 (sv) | 2001-10-19 | 2001-10-19 | Astrazeneca Ab | Rosuvastatin in pre demented states |
| KR100511533B1 (ko) | 2002-04-09 | 2005-08-31 | 임광민 | 키랄 중간체, 그의 제조방법 및 그를 이용한 HMG-CoA환원저해제의 제조방법 |
| EA200401533A1 (ru) | 2002-05-21 | 2005-06-30 | Ранбакси Лабораторис Лимитед | Способ получения росувастатина |
| GB0218781D0 (en) * | 2002-08-13 | 2002-09-18 | Astrazeneca Ab | Chemical process |
| DK1578733T3 (da) | 2002-12-10 | 2011-06-14 | Ranbaxy Lab Ltd | Fremgangsmåde til fremstilling af rosuvastatin |
| WO2005021511A1 (en) | 2003-08-27 | 2005-03-10 | Hetero Drugs Limited | A novel process for amorphous rosuvastatin calcium |
| EP1678148A1 (en) | 2003-10-22 | 2006-07-12 | Ranbaxy Laboratories Limited | Process for the preparation of amorphous rosuvastatin calcium |
| CA2546701C (en) | 2003-11-24 | 2010-07-27 | Teva Pharmaceutical Industries Ltd. | Crystalline ammonium salts of rosuvastatin |
| CN1894221B (zh) * | 2003-12-02 | 2012-08-08 | 特瓦制药工业有限公司 | 用于表征罗苏伐他汀的参照标准品 |
| EP1797046A2 (en) | 2004-09-27 | 2007-06-20 | Ranbaxy Laboratories Limited | Novel processes for preparing amorphous rosuvastatin calcium and a novel polymorphic form of rosuvastatin sodium |
| WO2006079611A1 (en) | 2005-01-31 | 2006-08-03 | Ciba Specialty Chemicals Holding Inc. | Crystalline forms of rosuvastatin calcium salt |
| WO2006100689A1 (en) | 2005-03-22 | 2006-09-28 | Unichem Laboratories Limited | Process for preparation of rosuvastatin |
| WO2006106526A1 (en) | 2005-04-04 | 2006-10-12 | Unichem Laboratories Limited | Process for preparation of calcium salt of rosuvastatin |
| WO2006136408A2 (en) | 2005-06-24 | 2006-12-28 | Lek Pharmaceuticals D.D. | Process for preparing pure amorphous rosuvastatin calcium |
| CA2612587C (en) | 2005-06-24 | 2013-02-19 | Lek Pharmaceuticals D.D. | Process for preparing amorphous rosuvastatin calcium free of impurities |
| GB0514078D0 (en) | 2005-07-08 | 2005-08-17 | Astrazeneca Uk Ltd | Chemical process |
-
2004
- 2004-12-02 CN CN2004800359220A patent/CN1894221B/zh not_active Expired - Fee Related
- 2004-12-02 KR KR1020067013302A patent/KR100887264B1/ko not_active Expired - Fee Related
- 2004-12-02 ES ES04812772T patent/ES2364143T3/es not_active Expired - Lifetime
- 2004-12-02 CA CA002546894A patent/CA2546894C/en not_active Expired - Fee Related
- 2004-12-02 PT PT04812772T patent/PT1689723E/pt unknown
- 2004-12-02 US US11/001,912 patent/US7244844B2/en not_active Expired - Lifetime
- 2004-12-02 AT AT04812772T patent/ATE507209T1/de not_active IP Right Cessation
- 2004-12-02 TW TW093137210A patent/TWI351958B/zh not_active IP Right Cessation
- 2004-12-02 DE DE602004032465T patent/DE602004032465D1/de not_active Expired - Lifetime
- 2004-12-02 EP EP04812772A patent/EP1689723B1/en not_active Revoked
- 2004-12-02 WO PCT/US2004/040329 patent/WO2005056534A1/en not_active Ceased
- 2004-12-02 JP JP2006541502A patent/JP4733047B2/ja not_active Expired - Fee Related
-
2006
- 2006-05-09 IL IL175511A patent/IL175511A/en active IP Right Grant
-
2007
- 2007-06-25 US US11/821,968 patent/US7692008B2/en not_active Expired - Fee Related
- 2007-06-25 US US11/823,019 patent/US7692009B2/en not_active Expired - Fee Related
- 2007-06-25 US US11/823,045 patent/US7692010B2/en not_active Expired - Fee Related
- 2007-06-25 US US11/823,013 patent/US7741482B2/en not_active Expired - Fee Related
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2009
- 2009-01-27 US US12/322,042 patent/US8487097B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20070255059A1 (en) | 2007-11-01 |
| ATE507209T1 (de) | 2011-05-15 |
| CA2546894A1 (en) | 2005-06-23 |
| IL175511A0 (en) | 2006-09-05 |
| US7692008B2 (en) | 2010-04-06 |
| US7692010B2 (en) | 2010-04-06 |
| JP4733047B2 (ja) | 2011-07-27 |
| EP1689723A1 (en) | 2006-08-16 |
| EP1689723B1 (en) | 2011-04-27 |
| US8487097B2 (en) | 2013-07-16 |
| US20090188305A1 (en) | 2009-07-30 |
| JP2007512354A (ja) | 2007-05-17 |
| US20070244321A1 (en) | 2007-10-18 |
| CA2546894C (en) | 2009-09-08 |
| US20070249831A1 (en) | 2007-10-25 |
| US7692009B2 (en) | 2010-04-06 |
| WO2005056534A1 (en) | 2005-06-23 |
| US7244844B2 (en) | 2007-07-17 |
| ES2364143T3 (es) | 2011-08-25 |
| US20070249830A1 (en) | 2007-10-25 |
| US7741482B2 (en) | 2010-06-22 |
| TW200522959A (en) | 2005-07-16 |
| PT1689723E (pt) | 2011-07-06 |
| DE602004032465D1 (de) | 2011-06-09 |
| KR20060098396A (ko) | 2006-09-18 |
| US20050187234A1 (en) | 2005-08-25 |
| CN1894221B (zh) | 2012-08-08 |
| CN1894221A (zh) | 2007-01-10 |
| KR100887264B1 (ko) | 2009-03-06 |
| TWI351958B (en) | 2011-11-11 |
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