Orlistat CAS 96829-58-2 API Weight Loss Drug Purity 98.0~101.5%

Orlistat
C29H53NO5 495.73
l-Leucine, N-formyl-, 1- [(3-hexyl-4-oxo-2-oxetanyl)methyl]dodecyl ester, [2S-[2(R*), 3]]-;
N-Formyl-l-leucine, ester ine (3S,4S) -3-hexyl-4-[(2S) -2-hydroxytridecyl] -2-oxetanone [96829-58-2].
DEFINITION
Orlistat ine NLT 98.0% uye NMT 101.5% yeC29H53NO5, yakaverengerwa pane anhydrous, solvent-isina hwaro.
KUZIVA
• A. Infrared Absorption <197M>
• B. Nguva yekuchengeta yenhongonya huru yeSample solution inoenderana neiyo yeStandard solution, sezvakawanikwa muAssay.
ASSAY
• Maitiro
[Cherechedza-Dzivisa kushandisa maflask epurasitiki kugadzirira kana kutakura chero mhinduro mukuongorora uku.]
Nharembozha: Acetonitrile, phosphoric acid, uye mvura (860: 0.05: 140)
Yakajairika mhinduro: 0.5 mg/mL yeUSP Orlistat RS muMobile phase.Jekiseni pakarepo mushure mekugadzirira kana chengetedza pa5.
Sample solution: 0.5 mg/mL yeOrlistat muMobile phase.Jekiseni pakarepo mushure mekugadzirira kana chengetedza pa5.
Chromatographic system
(Ona Chromatography <621>, System Suitability.)
Modhi: LC
Detector: UV 195
Column: 3.9-mm × 15-cm;4-µm kurongedza L1
Kuyerera kweyero: 1.0 mL/min
Jekiseni saizi: 20 µL
Kukodzera kwehurongwa
Muenzaniso: Standard solution
Kukodzera zvinodiwa
Kutsauswa muyero: NMT 2.0%
Analysis
Samples: Yakajairwa mhinduro uye Sample mhinduro
Verenga iyo muzana yeorlistat (C29H53NO5) muchikamu cheOrlistat chakatorwa:
Mhedzisiro = (rU/rS) × (CS/CU) × 100
rU = peak mhinduro kubva kuSample solution
rS = mhinduro yepamusoro kubva kune Standard solution
CS = kuungana kweUSP Orlistat RS muiyo Standard solution (mg/mL)
CU = kusangana kweOrlistat muSample solution (mg/mL)
Maitiro ekugamuchira: 98.0% -101.5% pane anhydrous, solvent-isina hwaro
KUSIRIRA
Inorganic Impurities
• Zvakasara paKubatidza <281>: NMT 0.1%
• Heavy Metals, Nzira II <231>: 20 ppm
Organic Kusachena
• Maitiro 1: Muganho weOrlistat Related Compound A
Yakajairwa mhinduro: 0.1 mg/mL yeUSP Orlistat Inoenderana Compound A RS muacetone
Sample solution: 50 mg/mL yeOrlistat muacetone
Chromatographic system
(Ona Chromatography <621>, Thin-Layer Chromatography.)
Modhi: TLC
Adsorbent: 0.25-mm layer yechromatographic silica gel musanganiswa
vhoriyamu yekushandisa: 10 µL
Kugadzira solvent system: Toluene uye ethyl acetate (4: 1)
Detection solution: Fambisa 2.5 g yephosphomolybdic acid uye 1 g yecerric sulfate mu100-mL volumetric flask, nyunguduka uye wedzera methanol kusvika kuhuwandu.
Analysis
Samples: Yakajairwa mhinduro uye Sample mhinduro
Bvisa ndiro, uye mhepo-inoomesa zvakakwana.Pfaya ndiro yakaomeswa neDetection solution, woisa ndiro yacho muchoto pa120 ye30 min.
Maitiro ekugamuchira: Chero nzvimbo yechipiri kubva kuSample solution inoenderana neorlistat ine hukama mukomboni A haina kusimba kupfuura iyo inoenderana nzvimbo kubva kune Standard solution (0.2%).
• Maitiro 2: Muganho weOrlistat Related Compound B
Mhinduro yakajairwa: 0.025 mg/mL yeUSP Orlistat Inoenderana Musanganiswa B RS mumethylene chloride
Sample solution: 50 mg/mL yeOrlistat mumethylene chloride
Spiked sampuli mhinduro: 50 mg/mL yeOrlistat mu Standard solution
Chromatographic system
(Ona Chromatography <621>, System Suitability.)
Modhi: GC
Detector: Moto ionization
Koramu: 0.32-mm x 30-m yakasanganiswa silica, yakaputirwa ne0.25-µm G27 yakamira chikamu
Column tembiricha: Ona tembiricha yepurogiramu tafura pazasi.
Yekutanga Tembiricha () Temperature Ramp (/min) Yekupedzisira Tembiricha () Bata Nguva Pakunopedzisira Tembiricha (min)
50 4 170 -
170 30 300 30
Tembiricha
Injector: 270
Detector: 280
Mutakuri gasi: Helium
Kuyerera: 30 mL / min
Kupatsanura ratio: 10:1
Jekiseni saizi: 2 µL
Kukodzera kwehurongwa
Muenzaniso: Standard solution
Kukodzera zvinodiwa
Kutsauswa kwechiyereko: NMT 10.0%
Analysis
Samples: Sample solution uye Spiked sample solution
Verenga iyo muzana yeorlistat inoenderana nekamu B muchikamu cheOrlistat chakatorwa:
Mhedzisiro = [rU/(rSP rU)] × (CS/CT) × 100
rU = peak mhinduro ye orlistat ine hukama B kubva kuSample solution
rSP = peak mhinduro yeorlistat ine hukama B kubva kune Spiked sampuli mhinduro
CS = kuunganidzwa kweUSP Orlistat Inoenderana Musanganiswa B RS muiyo Standard mhinduro (mg/mL)
CT = kusangana kweOrlistat muSpiked sampuli mhinduro (mg/mL)
Maitiro ekugamuchira: NMT 0.05% ye orlistat ine hukama nekomboni B inowanikwa.
• Maitiro 3
[Cherechedza-Dzivisa kushandisa maflask epurasitiki kugadzirira kana kutakura chero mhinduro mukuongorora uku.]
Nharembozha chikamu, Yakajairwa mhinduro, uye Sample mhinduro: Gadzirira sekurairwa muAssay.
Kukodzera kweSystem mhinduro: 10 µg/mL yeUSP Orlistat RS, 0.1 µg/mL yeUSP Orlistat Inoenderana NeCompound C RS, uye 0.25 µg/mL yeUSP Orlistat Inoenderana Compound D RS muMobile phase.
Chromatographic system
(Ona Chromatography <621>, System Suitability.)
Enderera sekurairwa muAssay, kunze kweku chromatograph iyo System kukodzera mhinduro.
Kukodzera kwehurongwa
Sample: System kukodzera mhinduro
Kukodzera zvinodiwa
Chiratidzo-ku-ruzha chiyero: NLT 3 yeiyo orlistat ine hukama mukomboni C uye orlistat ine hukama nemubatanidzwa D peaks
Relative mwero kutsauka: NMT 10.0% yeiyo orlistat peak
Analysis
Samples: Yakajairwa mhinduro uye Sample mhinduro
Verengai muzana yekusachena kwega kwega muchikamu cheOrlistat chakatorwa:
Mhedzisiro = (rU/rS) × (CS/CU) × (1/F) × 100
rU = peak mhinduro yekusachena yega yega kubva kuSample solution
rS = mhinduro yepamusoro yeUSP Orlistat RS kubva kune Standard solution
CS = kuungana kweUSP Orlistat RS muiyo Standard solution (mg/mL)
CU = kusangana kweOrlistat muSample solution (mg/mL)
F = hama yekupindura chinhu sezvakapihwa muKusachena Tafura 1
Maitiro ekugamuchira: Ona Kusachena Tafura 1.
Kusachena Tafura 1
Zita Nechekuchengeta Nguva Yehukama Mhinduro Factor Yekugamuchirwa, NMT (%)
Formylleucinea 0.10 4.0 0.2
Orlistat yakabatana musanganiswa C 0.13 33 0.05
Orlistat yakavhurika mhete epimerb 0.44 1.0 0.2
Orlistat yakabatana musanganiswa D * 0.90 - Yakaverengerwa mukati
Maitiro 4
Orlistat yakavhurika mhete amidec * 0.90 - Yakaverengerwa mukati
Maitiro 4
Orlistat 1.00 - -
d-Leucine orlistatd 1.18 1.0 0.2
Kusachena kwemunhu kusingazivikanwe - 1.0 0.1
* Coelutes mune ino LC system, yakatemwa kushandisa Procedure 4.
N-Formyl-l-leucine.
b (2S,3R,5S) -5-[(S)-2-Formylamino-4-methyl-pentanoyloxy] -2-hexyl-3-hydroxy-hexadecanoic acid.
c N-Formyl-l-leucine (S) -1-[(2S,3S)-2-hydroxy-3--[1-phenyl-R-ethylcarbomoyl]nonyl]-dodecyl ester.
d N-Formyl-d-leucine (S) -1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester kana enantiomer.
• Maitiro 4: Muganho weOrlistat Related Compound D
Nharembozha chikamu: Methanol nemvura (83:17)
Sistimu yekukodzera mhinduro: 4 mg/mL yeUSP Orlistat RS uye 2.4 µg/mL yeUSP Orlistat Inoenderana Compound D RS muacetonitrile, zvichiteerana
Mhinduro yakajairwa: 5.0 mg/mL yeUSP Orlistat RS muacetonitrile
Sample solution: 5.0 mg/mL yeOrlistat muacetonitrile
Chromatographic system
(Ona Chromatography 621, System Suitability.)
Modhi: LC
Detector: 205 nm
Column: 4.0-mm × 25-cm;5-µm kurongedza L7
Kuyerera kweyero: 0.6 mL/min
Jekiseni saizi: 20 µL
Kukodzera kwehurongwa
Sample: System kukodzera mhinduro
Kukodzera zvinodiwa
Chiratidzo-ku-ruzha chiyero: NLT 3 yeiyo orlistat ine hukama mukomboni D peak
Relative mwero kutsauka: NMT 10.0% yeiyo orlistat peak
Analysis
Samples: Yakajairwa mhinduro uye Sample mhinduro
Verengai muzana yekusachena kwega kwega muchikamu cheOrlistat chakatorwa:
Mhedzisiro = (rU/rS) × (CS/CU) × (1/F) × 100
rU = peak mhinduro yekusachena yega yega kubva kuSample solution
rS = peak mhinduro yeUSP Orlistat RS kubva kune Standard solution
CS = kuunganidzwa kweUSP Orlistat RS muiyo Standard solution (µg/mL)
CU = kusangana kweOrlistat muSample solution (µg/mL)
F = hama yekupindura chinhu sezvakawanikwa muKusachena Tafura 2
Maitiro ekugamuchira: Ona Kusachena Tafura 2.
Kusachena Tafura 2
Zita Nechekuchengeta Nguva Yehukama Mhinduro Factor Yekugamuchirwa, NMT (%)
Orlistat inoenderana musanganiswa D 0.94 1.0 0.2
Orlistat 1.00 - -
Orlistat yakavhurika mhete amidea 1.25 4.3 0.1
a N-Formyl-l-leucine (S) -1-[(2S,3S) -2-hydroxy-3--[1-phenyl-R-ethylcarbomoyl]nonyl]-dodecyl ester.
• Maitiro 5: Muganho weOrlistat Related Compound E
Buffer: 0.4 N borate mhinduro, yakagadziridzwa kune pH ye10.2
Derivitizing agent: o-Phthaldehyde (OPA) mhinduro.[Cherechedza-Kana usingakwanise kuwana zvekutengesa, iyo Derivitizing agent inogona kugadzirwa se1% imwe neimwe ye3-mercaptopropionic acid uye o-phthaldialdehyde mu0.4 M borate buffer solution.]
Mhinduro A: Kuendesa 4.1 g ye sodium acetate trihydrate uye 40 mg ye ethylenediaminetetraacetic acid (EDTA) mu 1-L volumetric flask.Dissolve mu950 mL yemvura, uye gadzirisa ne 0.1 N sodium hydroxide kusvika pH ye7.2.Dhonza nemvura kusvika kuhuwandu, wedzera 2.5 mL ye tetrahydrofuran, uye sanganisa.Sefa, uye degas.
Mhinduro B: Tumira 2.7 g ye sodium acetate trihydrate uye 40 mg yeEDTA mu 1-L volumetric flask.Dissolve mu 200 mL yemvura, uye gadzirisa ne 0.1 N sodium hydroxide kusvika pH ye7.2.Wedzera 800 mL yeacetonitrile, sefa, uye degas.
Nharembozha: Ona tafura yegradient pazasi.
Nguva (min) Solution A (%) Solution B (%)
0 96.7 3.3
20 60 40
24 0 100
38 0 100
38 96.7 3.3
45 96.7 3.3
Mhinduro yakajairwa: Tumira huwandu hwakayerwa hunosvika 0.2 mg yeUSP Orlistat Inoenderana kompani E RS mune 20-mL yemusoro-nzvimbo vial.Wedzera 10 mL ye4 N sodium hydroxide, uye vhara vial.Pisa vial kusvika ku100 kwe1 h, wozobvumira kutonhora kusvika kukamuri tembiricha.Chinja 2 mL yemhinduro inoguma mu50-mL volumetric flask, uye dilue nemvura kusvika kuhuwandu.Ku 0.5 mL yemhinduro iyi wedzera 2.0 mL yeBuffer uye 0.5 mL yeDerivatizing agent.
Sample solution: Ramba uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchingedzerwa kune iyo Standard solution, asi panzvimbo pacho shandisa 25 mg yeOrlistat kutsiva iyo 0.2 mg yeUSP Orlistat Related Compound E RS.
Chromatographic system
(Ona Chromatography <621>, System Suitability.)
Modhi: LC
Detector: Fluorescence 340 nm (excitation);450 nm (kubuda)
Columns
Murindi: 2.1-mm × 2-cm;50-µm kurongedza L1
Analytical: 2.1-mm × 20-cm;kurongedza L1
Kuyerera kweyero: 0.5 mL/min
Jekiseni saizi: 20 µL
Kukodzera kwehurongwa
Muenzaniso: Standard solution
Kukodzera zvinodiwa
Relative mwero kutsauka: NMT 6.0% ye orlistat ine hukama mukomboni E peak
Analysis
Samples: Yakajairwa mhinduro uye Sample mhinduro
Verengai muzana yekusachena uku muchikamu cheOrlistat chakatorwa:
Mhedzisiro = (rU/rS) × (CS/CU) × 100
rU = peak mhinduro yeorlistat inoenderana nekamu E mune Sample mhinduro
rS = peak mhinduro yeUSP Orlistat Inoenderana Musanganiswa E RS mune iyo Standard mhinduro
CS = kuunganidzwa kweUSP Orlistat Inoenderana Musanganiswa E RS muiyo Standard mhinduro (mg/mL)
CU = kusangana kweOrlistat muSample solution (mg/mL)
Maitiro ekugamuchira
Kusachena kwemunhu: NMT 0.2% ye orlistat ine chekuita nemubatanidzwa E inowanikwa.
Hutsvina hwose: NMT 1.0% yetsvina yese inowanikwa, mibairo yeMatanho 1, 2, 3, 4, ne5 ichiwedzerwa.
ZVIYEDZO ZVAKANAKA
• Optical Rotation, Specific Rotation <781>
Sample solution: 30 mg/mL mudoro risina mvura
Maitiro ekugamuchira: Pakati -48.0 uye -51.0, pa20
• Kusarudza Mvura, Nzira Ic <921>: NMT 0.2%
ZVIMWE ZVINODIWA
• Kurongedza uye Kuchengeta: Chengetedza mumidziyo yakavharwa zvakanaka pakati pe2 ne8℃.
• USP Reference Standards <11>
USP Orlistat RS
USP Orlistat Inoenderana Musanganiswa A RS
USP Orlistat Inoenderana Musanganiswa B RS
USP Orlistat Inoenderana Musanganiswa C RS
USP Orlistat Inoenderana Musanganiswa D RS
USP Orlistat Inoenderana Musanganiswa E RS
USP35