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

I-Orlistat
C29H53NO5 495.73
l-Leucine, N-formyl-, 1-[(3-hexyl-4-oxo-2-oxetanyl)methyl]dodecyl ester, [2S-[2(R*), 3]]-;
I-N-Formyl-l-leucine, i-ester ene-(3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]-2-oxetanone [96829-58-2].
INCAZELO
I-Orlistat iqukethe i-NLT 98.0% kanye ne-NMT 101.5% ye-C29H53NO5, ibalwe ngesisekelo se-anhydrous, esingenayo i-solvent.
UKUKHOMBA
• A. I-Infrared Absorption <197M>
• B. Isikhathi sokugcina sesiqongo esikhulu sesixazululo Sesampuli sihambisana naleso Sesixazululo Esijwayelekile, njengoba sitholwe ku-Assay.
ISIVIVINYO
• Inqubo
[Qaphela-Gwema ukusetshenziswa kwamaflask epulasitiki ukulungisa noma ukuqukatha noma yisiphi isisombululo kulokhu kuhlaziya.]
Isigaba seselula: I-Acetonitrile, i-phosphoric acid, namanzi (860: 0.05: 140)
Isixazululo esijwayelekile: 0.5 mg/mL ye-USP Orlistat RS esigabeni Seselula.Jova ngokushesha ngemva kokulungiselela noma ugcine ngo-5.
Isixazululo sesampula: 0.5 mg/mL ye-Orlistat esigabeni Seselula.Jova ngokushesha ngemva kokulungiselela noma ugcine ngo-5.
Isistimu yeChromatographic
(Bona i-Chromatography <621>, Ukufaneleka Kwesistimu.)
Imodi: LC
Umtshina: UV 195
Ikholomu: 3.9-mm × 15-cm;4-µm ukupakisha L1
Izinga lokugeleza: 1.0 mL/min
Usayizi womjovo: 20 µL
Ukufaneleka kwesistimu
Isampula: Isixazululo esijwayelekile
Izidingo zokufaneleka
Ukuchezuka okujwayelekile okuhlobene: NMT 2.0%
Ukuhlaziya
Amasampula: Isixazululo esijwayelekile kanye nesixazululo esiyisampula
Bala iphesenti le-orlistat (C29H53NO5) engxenyeni ye-Orlistat ethathiwe:
Umphumela = (rU/rS) × (CS/CU) × 100
rU = impendulo ephezulu evela kusixazululo Sesampula
rS = impendulo ephezulu evela kusixazululo Esijwayelekile
CS = ukugxila kwe-USP Orlistat RS kusixazululo Esijwayelekile (mg/mL)
I-CU = ukuhlushwa kwe-Orlistat kusixazululo Sesampula (mg/mL)
Imibandela yokwamukela: 98.0% -101.5% kusisekelo se-anhydrous, esingancibiliki
UKUNGCOLA
Ukungcola Okungaphili
• Insalela Ekuthutheni <281>: NMT 0.1%
• Izinsimbi Ezisindayo, Indlela II <231>: 20 ppm
Ukungcola Okuphilayo
• Inqubo 1: Umkhawulo Wenhlanganisela Ehlobene Ne-Orlistat A
Isixazululo esijwayelekile: 0.1 mg/mL ye-USP Orlistat Related Compound A RS ku-acetone
Isixazululo sesampula: 50 mg/mL ye-Orlistat ku-acetone
Isistimu yeChromatographic
(Bona i-Chromatography <621>, I-Thin-Layer Chromatography.)
Imodi: TLC
I-Adsorbent: 0.25-mm ungqimba lwengxube yejeli yesilica yechromatographic
Ivolumu yohlelo lokusebenza: 10 µL
Ukuthuthukisa uhlelo lokuncibilikisa: I-Toluene ne-ethyl acetate (4:1)
Isixazululo sokuthola: Dlulisa u-2.5 g we-phosphomolybdic acid no-1 g we-cerric sulfate ku-100-mL ye-volumetric flask, hlakazeka futhi uhlambulule nge-methanol kuvolumu.
Ukuhlaziya
Amasampula: Isixazululo esijwayelekile kanye nesixazululo esiyisampula
Susa ipuleti, bese ulomisa emoyeni kahle.Fafaza ipuleti elomile ngesisombululo se-Detection, bese ubeka ipuleti kuhhavini ekushiseni okungu-120 imizuzu engama-30.
Imibandela yokwamukela: Noma iyiphi indawo yesibili evela kusixazululo Sesampula esihambisana nenhlanganisela ehlobene ne-orlistat A ayinamandla kakhulu kunendawo ehambisanayo evela kusixazululo Esijwayelekile (0.2%).
• Inqubo 2: Umkhawulo Wenhlanganisela Ehlobene Ne-Orlistat B
Isixazululo esijwayelekile: 0.025 mg/mL ye-USP Orlistat Related Compound B RS ku-methylene chloride
Isixazululo sesampula: 50 mg/mL ye-Orlistat ku-methylene chloride
Isixazululo sesampula esiphundu: 50 mg/mL ye-Orlistat kusixazululo Esijwayelekile
Isistimu yeChromatographic
(Bona i-Chromatography <621>, Ukufaneleka Kwesistimu.)
Imodi: GC
Umtshina: I-ionization yomlilo
Ikholomu: 0.32-mm x 30-m silica ehlanganisiwe, embozwe ngesigaba sokuma esingu-0.25-µm G27
Izinga lokushisa lekholomu: Bona ithebula lohlelo lokushisa ngezansi.
Ithempelesha Yokuqala () Irempu Yezinga lokushisa (/min) Izinga Lokushisa Lokugcina () Ukubamba Isikhathi Emazingeni Okushisa Okugcina (imizuzu)
50 4 170 -
170 30 300 30
Izinga lokushisa
Umjovo: 270
Umtshina: 280
Igesi yenkampani: i-Helium
Izinga lokugeleza: 30 mL/min
Isilinganiso sokuhlukaniswa: 10:1
Usayizi womjovo: 2 µL
Ukufaneleka kwesistimu
Isampula: Isixazululo esijwayelekile
Izidingo zokufaneleka
Ukuchezuka okujwayelekile okuhlobene: NMT 10.0%
Ukuhlaziya
Amasampula: Isixazululo sesampula kanye nesixazululo sesampula esi-Spiked
Bala iphesenti lenhlanganisela B ehlobene ne-orlistat engxenyeni ye-Orlistat ethathiwe:
Umphumela = [rU/(rSP rU)] × (CS/CT) × 100
rU = impendulo ephakeme ye-orlistat ehlobene ne-compound B kusuka kusixazululo seSampula
I-rSP = impendulo ephezulu ye-orlistat ehlobene nenhlanganisela B kusuka kusixazululo sesampula se-Spiked
CS = ukugxila kwe-USP Orlistat Ehlobene Inhlanganisela B RS kusixazululo Esijwayelekile (mg/mL)
I-CT = ukugcwala kwe-Orlistat kusixazululo sesampula se-Spiked (mg/mL)
Imibandela yokwamukela: I-NMT 0.05% yenhlanganisela B ehlobene ne-orlistat iyatholakala.
• Inqubo 3
[Qaphela-Gwema ukusetshenziswa kwamaflask epulasitiki ukulungisa noma ukuqukatha noma yisiphi isisombululo kulokhu kuhlaziya.]
Isigaba seselula, isixazululo esijwayelekile, nesixazululo esiyisampula: Lungiselela njengoba kuqondiswe ku-Assay.
Isixazululo sokufaneleka kwesistimu: 10 µg/mL ye-USP Orlistat RS, 0.1 µg/mL ye-USP Orlistat Related Compound C RS, kanye no-0.25 µg/mL ye-USP Orlistat Related Compound D RS esigabeni Seselula
Isistimu yeChromatographic
(Bona i-Chromatography <621>, Ukufaneleka Kwesistimu.)
Qhubeka njengoba kushiwo ku-Assay, ngaphandle kokufaka i-chromatograph isisombululo sokufaneleka Kwesistimu.
Ukufaneleka kwesistimu
Isampula: Isixazululo sokufaneleka kwesistimu
Izidingo zokufaneleka
Isilinganiso somsindo wesignali: I-NLT 3 yenhlanganisela C ehlobene ne-orlistat kanye neziqongo ezihambisana ne-orlistat ehlobene
Ukuchezuka okujwayelekile okuhlobene: I-NMT 10.0% yenani eliphakeme le-orlistat
Ukuhlaziya
Amasampula: Isixazululo esijwayelekile kanye nesixazululo esiyisampula
Bala iphesenti lokungcola ngakunye engxenyeni ye-Orlistat ethathiwe:
Umphumela = (rU/rS) × (CS/CU) × (1/F) × 100
i-rU = impendulo ephezulu yokungcola komuntu ngamunye kusuka kusixazululo Sesampuli
rS = impendulo ephezulu ye-USP Orlistat RS evela kusixazululo Esijwayelekile
CS = ukugxila kwe-USP Orlistat RS kusixazululo Esijwayelekile (mg/mL)
I-CU = ukuhlushwa kwe-Orlistat kusixazululo Sesampula (mg/mL)
F = isici sokuphendula esihlobene njengoba sinikezwe kuThebula Lokungcola 1
Indlela yokwamukela: Bheka Ithebula Lokungcola 1.
Ithebula Lokungcola 1
Yisho Isikhathi Esihlobene Sokugcina Isikhathi Sendlela Yokwamukela Isici Sempendulo Ehlobene, i-NMT (%)
I-Formylleucinea 0.10 4.0 0.2
Inhlanganisela ehlobene ne-Orlistat C 0.13 33 0.05
I-Orlistat evulekile indandatho epimerb 0.44 1.0 0.2
Inhlanganisela ehlobene ne-Orlistat D* 0.90 - Ibalwa ku
Inqubo 4
I-Orlistat evulekile indandatho i-amidec* 0.90 - Ibalwa ngo
Inqubo 4
I-Orlistat 1.00 - -
I-d-Leucine orlistatd 1.18 1.0 0.2
Ukungcola komuntu ngamunye okungaziwa - 1.0 0.1
* Ama-Coelutes kulolu hlelo lwe-LC, anqunywa kusetshenziswa i-Procedure 4.
i-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 noma i-enantiomer.
• Inqubo 4: Umkhawulo Wenhlanganisela Ehlobene Ne-Orlistat D
Isigaba sikamakhalekhukhwini: I-Methanol namanzi (83:17)
Isixazululo sokufaneleka kwesistimu: 4 mg/mL ye-USP Orlistat RS kanye ne-2.4 µg/mL ye-USP Orlistat Inhlanganisela Ehlobene D RS ku-acetonitrile, ngokulandelanayo
Isixazululo esijwayelekile: 5.0 mg/mL ye-USP Orlistat RS ku-acetonitrile
Isixazululo sesampula: 5.0 mg/mL ye-Orlistat ku-acetonitrile
Isistimu yeChromatographic
(Bona i-Chromatography 621, Ukufaneleka Kwesistimu.)
Imodi: LC
Umtshina: 205 nm
Ikholomu: 4.0-mm × 25-cm;5-µm ukupakisha L7
Izinga lokugeleza: 0.6 mL/min
Usayizi womjovo: 20 µL
Ukufaneleka kwesistimu
Isampula: Isixazululo sokufaneleka kwesistimu
Izidingo zokufaneleka
Isilinganiso somsindo wesignali: I-NLT 3 yenhlanganisela ye-orlistat ehlobene nenani eliphakeme elingu-D
Ukuchezuka okujwayelekile okuhlobene: I-NMT 10.0% yenani eliphakeme le-orlistat
Ukuhlaziya
Amasampula: Isixazululo esijwayelekile kanye nesixazululo esiyisampula
Bala iphesenti lokungcola ngakunye engxenyeni ye-Orlistat ethathiwe:
Umphumela = (rU/rS) × (CS/CU) × (1/F) × 100
i-rU = impendulo ephezulu yokungcola komuntu ngamunye kusuka kusixazululo Sesampuli
rS = impendulo ephezulu ye-USP Orlistat RS evela kusixazululo Esijwayelekile
CS = ukugxila kwe-USP Orlistat RS kusixazululo Esijwayelekile (µg/mL)
I-CU = ukugcwala kwe-Orlistat kusixazululo Sesampula (µg/mL)
F = isici sokuphendula esihlobene njengoba sitholwe kuThebula 2 Lokungcola
Indlela yokwamukela: Bheka Ithebula 2 Lokungcola.
Ithebula Lokungcola 2
Yisho Isikhathi Esihlobene Sokugcina Isikhathi Sendlela Yokwamukela Isici Sempendulo Ehlobene, i-NMT (%)
Inhlanganisela ehlobene ne-Orlistat D 0.94 1.0 0.2
I-Orlistat 1.00 - -
I-Orlistat evulekile indandatho i-amidea 1.25 4.3 0.1
i-N-Formyl-l-leucine (S) -1-[(2S,3S)-2-hydroxy-3-[1-phenyl-R-ethylcarbomoyl]nonyl]-dodecyl ester.
• Inqubo 5: Umkhawulo Wenhlanganisela Ehlobene Ne-Orlistat E
Isigcinalwazi: 0.4 N isixazululo seborate, esilungiselwe ku-pH engu-10.2
I-ejenti ephumayo: isixazululo se-o-Phthaldehyde (OPA).[Qaphela-Uma ungakwazi ukuthola ngokwentengiso, i-ejenti ye-Derivitizing ingalungiswa njengo-1% ngayinye ye-3-mercaptopropionic acid ne-o-phthaldialdehyde kusixazululo sebhafa esingu-0.4 M borate.]
Isixazululo A: Dlulisa i-4.1 g ye-sodium acetate trihydrate kanye ne-40 mg ye-ethylenediaminetetraacetic acid (EDTA) ku-flask ye-volumetric engu-1-L.Chaza ku-950 mL wamanzi, futhi ulungise ne-0.1 N sodium hydroxide ku-pH engu-7.2.Nciphisa ngamanzi ngevolumu, engeza u-2.5 mL we-tetrahydrofuran, uhlanganise.Hlunga, kanye ne-degas.
Isixazululo B: Dlulisa u-2.7 g we-sodium acetate trihydrate kanye no-40 mg we-EDTA ku-flask ye-volumetric engu-1-L.Chaza ku-200 mL wamanzi, futhi ulungise ne-0.1 N sodium hydroxide ku-pH engu-7.2.Engeza u-800 mL we-acetonitrile, isihlungi, ne-degas.
Isigaba seselula: Bona ithebula legradient ngezansi.
Isikhathi (imizuzu) Isixazululo A (%) Isixazululo 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
Isixazululo esijwayelekile: Dlulisa inani elinesisindo esingaba ngu-0.2 mg we-USP Orlistat Inhlanganisela Ehlobene E RS ibe yibhodlela yesikhala sekhanda engu-20-mL.Engeza u-10 mL we-4 N sodium hydroxide, bese uvala ibhodlela.Shisisa i-vial ku-100 ihora elingu-1, bese uvumela ukupholisa ekamelweni lokushisa.Dlulisa u-2 mL wekhambi eliwumphumela ube yi-50-mL ye-volumetric flask, bese uhlanza ngamanzi ngevolumu.Ku-0.5 mL walesi sixazululo engeza u-2.0 mL we-Buffer kanye no-0.5 mL we-agent ephumayo.
Isixazululo sesampula: Qhubeka njengoba kuqondiswe kusixazululo Esijwayelekile, kodwa esikhundleni salokho sebenzisa i-25 mg ye-Orlistat ukuze ubeke esikhundleni se-0.2 mg ye-USP Orlistat Related Compound E RS.
Isistimu yeChromatographic
(Bona i-Chromatography <621>, Ukufaneleka Kwesistimu.)
Imodi: LC
Umtshina: I-Fluorescence 340 nm (i-excitation);450 nm (ukukhishwa)
Amakholomu
Umqaphi: 2.1-mm × 2-cm;50-µm ukupakisha L1
Ukuhlaziya: 2.1-mm × 20-cm;ukupakisha L1
Izinga lokugeleza: 0.5 mL/min
Usayizi womjovo: 20 µL
Ukufaneleka kwesistimu
Isampula: Isixazululo esijwayelekile
Izidingo zokufaneleka
Ukuchezuka okujwayelekile okuhlobene: I-NMT 6.0% yenhlanganisela Ehlobene ne-orlistat ephezulu
Ukuhlaziya
Amasampula: Isixazululo esijwayelekile kanye nesixazululo esiyisampula
Bala iphesenti lalokhu kungcola engxenyeni ye-Orlistat ethathiwe:
Umphumela = (rU/rS) × (CS/CU) × 100
I-rU = impendulo ephakeme ye-orlistat ehlobene ne-compound E kusixazululo Sesampula
rS = impendulo ephezulu ye-USP Orlistat Inhlanganisela Ehlobene E RS kusixazululo Esijwayelekile
CS = ukugxila kwe-USP Orlistat Ehlobene Inhlanganisela E RS kusixazululo Esijwayelekile (mg/mL)
I-CU = ukuhlushwa kwe-Orlistat kusixazululo Sesampula (mg/mL)
Imibandela yokwamukela
Ukungcola komuntu ngamunye: I-NMT 0.2% yenhlanganisela E ehlobene ne-orlistat iyatholakala.
Ukungcola okuphelele: I-NMT 1.0% yokungcola okuphelele kuyatholakala, imiphumela Yezinqubo 1, 2, 3, 4, kanye no-5 iyengezwa.
IZIVIVINYO EZITHILE
• I-Optical Rotation, Specific Rotation <781>
Isixazululo esiyisampula: 30 mg/mL kutshwala obungenawo amanzi
Imibandela yokwamukela: Phakathi -48.0 kanye -51.0, ku-20
• Ukunqunywa kwamanzi, Indlela Ic <921>: NMT 0.2%
IZIDINGO EZENGEZIWE
• Ukupakisha Nokugcina: Londoloza ezitsheni ezivalwe kahle phakathi kuka-2 no-8℃.
• I-USP Reference Standards <11>
I-USP Orlistat RS
I-USP Orlistat Inhlanganisela Ehlobene A RS
I-USP Orlistat Ehlobene Inhlanganisela B RS
I-USP Orlistat Inhlanganisela Ehlobene C RS
I-USP Orlistat Inhlanganisela Ehlobene D RS
I-USP Orlistat Inhlanganisela Ehlobene E RS
I-USP35