Orlistat CAS 96829-58-2 API Pa'u mamafa Fualaau Fa'amama 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 ma (3S,4S) -3-hexyl-4- [(2S) -2-hydroxytridecyl] -2-oxetanone [96829-58-2].
FAAMATALAGA
Orlistat o loʻo i ai le NLT 98.0% ma le NMT 101.5% o le C29H53NO5, faʻatatau i luga o le anhydrous, solvent-free basis.
FAATINOGA
• A. Infrared Absorption <197M>
• B. O le taimi fa'atumauina o le tumutumu tele o le fofo Fa'ata'ita'i e fetaui ma le vaifofo masani, e pei ona maua i le Su'ega.
SU'ESU'EGA
• Taualumaga
[Manatua-Aloese mai le fa'aogaina o fagu palasitika mo le tapenaga po'o le taofiofia o so'o se vaifofo i lenei su'esu'ega.]
Vaega feavea'i: Acetonitrile, phosphoric acid, ma vai (860: 0.05: 140)
Fofo masani: 0.5 mg/mL o le USP Orlistat RS i le vaega Mobile.Tu'i vave pe a uma ona tapena pe teu ile 5.
Fa'ata'ita'iga fofo: 0.5 mg/mL ole Orlistat ile vaega feavea'i.Tu'i vave pe a uma ona tapena pe teu ile 5.
Faiga fa'akomepiuta
(Va'ai Chromatography <621>, Faiga Fa'atonu.)
Auala: LC
Su'esu'e: UV 195
Koluma: 3.9-mm × 15-cm;4-µm fa'apipi'i L1
Fuafuaga tafe: 1.0 mL/min
Tele tui: 20 µL
Faiga talafeagai
Fa'ata'ita'iga: Fofo masani
Mana'oga talafeagai
Feso'ota'iga tulaga ese: NMT 2.0%
Iloiloga
Faʻataʻitaʻiga: Fofo masani ma Faʻataʻitaʻiga fofo
Fa'atatau le pasene ole orlistat (C29H53NO5) ile vaega ole Orlistat na ave:
I'uga = (rU/rS) × (CS/CU) × 100
rU = tali maualuga mai le faʻataʻitaʻiga fofo
rS = tali pito i luga mai le fofo masani
CS = fa'atonuga o le USP Orlistat RS i le fofo masani (mg/mL)
CU = fa'atonuga ole Orlistat ile fa'ata'ita'iga fofo (mg/mL)
Ta'iala talia: 98.0% -101.5% i luga ole vai, leai se solvent.
LELEI
Fa'aleaga Fa'aletino
• Toega ile mumu <281>: NMT 0.1%
• Uamea Mamafa, Metotia II <231>: 20 ppm
Oona Fa'aleaga
• Faiga 1: Tapula'a ole Orlistat Related Compound A
Fofo masani: 0.1 mg/mL o le USP Orlistat Related Compound A RS i le acetone
Fa'ata'ita'iga fofo: 50 mg/mL ole Orlistat ile acetone
Faiga fa'akomepiuta
(Silasila i le Chromatography <621>, Layer Layer Chromatography.)
Auala: TLC
Adsorbent: 0.25-mm apa o chromatographic silica gel paluga
Ole tele ole talosaga: 10 µL
Atia'e faiga so'o: Toluene ma ethyl acetate (4:1)
Su'esu'ega vaifofo: Fa'aliliu le 2.5 g o le phosphomolybdic acid ma le 1 g o le cerric sulfate i totonu o se fagu volumetric 100-mL, fa'amavae i totonu ma fa'afefiloi i le methanol i le voluma.
Iloiloga
Faʻataʻitaʻiga: Fofo masani ma Faʻataʻitaʻiga fofo
Aveese le ipu, ma fa'amago lelei.Sausau le ipu mamago i le Detection solution, ma tuu le ipu i totonu o se ogaumu i le 120 mo le 30 min.
Ta'iala Talia: So'o se vaega lona lua mai le Fa'ata'ita'iga fofo e fetaui ma le orlistat feso'ota'i fa'atasi A e le sili atu le malosi nai lo le tulaga tutusa mai le Fa'ata'ita'iga fofo (0.2%).
• Faiga 2: Tapula'a ole Orlistat Related Compound B
Fofo masani: 0.025 mg/mL o le USP Orlistat Related Compound B RS i le methylene chloride
Fa'ata'ita'iga fofo: 50 mg/mL ole Orlistat ile methylene chloride
Fofo faʻataʻitaʻiga faʻapipiʻi: 50 mg / mL o Orlistat i le fofo masani
Faiga fa'akomepiuta
(Va'ai Chromatography <621>, Faiga Fa'atonu.)
Auala: GC
Su'esu'e: Iona afi
Koluma: 0.32-mm x 30-m silika fa'afefiloi, ufiufi i le 0.25-µm G27 vaega tumau
O le vevela o le koluma: Va'ai le laulau o le polokalame vevela i lalo.
Vevela Muamua () Temperature Ramp (/min) Vevela Mulimuli () Taimi Taofi ile Vevela Mulimuli (min)
50 4 170 -
170 30 300 30
vevela
Iniseti: 270
Su'esu'e: 280
Kesi ave: Helium
Fuafuaga tafe: 30 mL/min
Vaevae fua: 10:1
Tele ole tui: 2 µL
Faiga talafeagai
Fa'ata'ita'iga: Fofo masani
Mana'oga talafeagai
Feso'ota'iga tulaga ese: NMT 10.0%
Iloiloga
Fa'ata'ita'iga: Fa'ata'ita'i fofo ma Spiked fa'ata'ita'iga fofo
Fuafua le pasene o le orlistat e fesoʻotaʻi faʻatasi B i le vaega ole Orlistat na ave:
I'uga = [rU/(rSP rU)] × (CS/CT) × 100
rU = tali pito i luga ole vaega ole orlistat feso'ota'i B mai le fa'ata'ita'iga fofo
rSP = tali pito i luga ole vaega ole orlistat feso'ota'i B mai le fofo fa'ata'ita'i Spiked
CS = fa'amaualuga o le USP Orlistat Related Compound B RS i le vaifofo masani (mg/mL)
CT = fa'atonuga ole Orlistat ile fofo fa'ata'ita'i Spiked (mg/mL)
Ta'iala e talia ai: NMT 0.05% ole vaega ole orlistat B e maua.
• Faiga 3
[Manatua-Aloese mai le fa'aogaina o fagu palasitika mo le tapenaga po'o le taofiofia o so'o se vaifofo i lenei su'esu'ega.]
Vaega feavea'i, Fofo masani, ma Fa'ata'ita'iga fofo: Saunia e pei ona fa'atonuina ile Su'ega.
Fofo talafeagai faiga: 10 µg/mL o le USP Orlistat RS, 0.1 µg/mL o le USP Orlistat Related Compound C RS, ma le 0.25 µg/mL o le USP Orlistat Related Compound D RS i le vaega feavea'i
Faiga fa'akomepiuta
(Va'ai Chromatography <621>, Faiga Fa'atonu.)
Fa'agasolo e pei ona fa'atonuina i le Su'esu'ega, se'i vagana ai le chromatograph le fofo talafeagai Faiga.
Faiga talafeagai
Fa'ata'ita'iga: Fa'atonuga fa'aoga fofo
Mana'oga talafeagai
Fa'ailo-i-leo pisapisao: NLT 3 mo le orlistat feso'ota'i fa'atasi C ma orlistat feso'ota'i fa'aputuga D tumutumu
Feso'ota'iga tulaga fa'atusa: NMT 10.0% mo le pito i luga ole orlistat
Iloiloga
Faʻataʻitaʻiga: Fofo masani ma Faʻataʻitaʻiga fofo
Faʻatusatusa le pasene o mea leaga taʻitasi i le vaega ole Orlistat na ave:
I'uga = (rU/rS) × (CS/CU) × (1/F) × 100
rU = tali maualuga mo tagata taʻitoʻatasi le mama mai le Sample solution
rS = tali maualuga a le USP Orlistat RS mai le vaifofo Tulaga
CS = fa'atonuga o le USP Orlistat RS i le fofo masani (mg/mL)
CU = fa'atonuga ole Orlistat ile fa'ata'ita'iga fofo (mg/mL)
F = fa'atatau tali tali e pei ona tu'uina atu i le Fa'aleaga Siata 1
Ta'iala e talia: Va'ai Fuafuaga Le mama 1.
Fa'aleaga Laulau 1
Igoa Taimi Taofi Fa'atatau Fa'atatau Tali Tali Fa'atatau Fa'atalia, NMT (%)
Formylleucinea 0.10 4.0 0.2
Orlistat feso'ota'i fa'atasi C 0.13 33 0.05
Orlistat mama tatala epimerb 0.44 1.0 0.2
Orlistat feso'ota'iga fa'atasi D* 0.90 - Fa'atatau ile
Taualumaga 4
Orlistat mama tatala amidec* 0.90 - Fa'atatau ile
Taualumaga 4
Orlistat 1.00 - -
d-Leucine orlistatd 1.18 1.0 0.2
Ta'ito'atasi le fa'ailoaina le mama - 1.0 0.1
* Coelutes i lenei faiga LC, fuafuaina e faʻaaoga ai le Faiga 4.
o se 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 poʻo enantiomer.
• Faiga 4: Tapula'a ole Orlistat Related Compound D
Vaega feavea'i: Methanol ma vai (83:17)
Fofo fa'aoga talafeagai: 4 mg/mL o le USP Orlistat RS ma le 2.4 µg/mL o le USP Orlistat Related Compound D RS i le acetonitrile, fa'asologa.
Fofo masani: 5.0 mg/mL o le USP Orlistat RS ile acetonitrile
Fa'ata'ita'iga fofo: 5.0 mg/mL ole Orlistat ile acetonitrile
Faiga fa'akomepiuta
(Va'ai Chromatography 621, Faiga Fa'atonu.)
Auala: LC
Su'esu'e: 205 nm
Koluma: 4.0-mm × 25-cm;5-µm fa'apipi'i L7
Fuafuaga tafe: 0.6 mL/min
Tele tui: 20 µL
Faiga talafeagai
Fa'ata'ita'iga: Fa'atonuga fa'aoga fofo
Mana'oga talafeagai
Fa'ailo i le pisa: NLT 3 mo le fa'aputuga D pito i luga ole orlistat
Feso'ota'iga tulaga fa'atusa: NMT 10.0% mo le pito i luga ole orlistat
Iloiloga
Faʻataʻitaʻiga: Fofo masani ma Faʻataʻitaʻiga fofo
Faʻatusatusa le pasene o mea leaga taʻitasi i le vaega ole Orlistat na ave:
I'uga = (rU/rS) × (CS/CU) × (1/F) × 100
rU = tali maualuga mo tagata taʻitoʻatasi le mama mai le Sample solution
rS = tali pito i luga mo USP Orlistat RS mai le fofo masani
CS = fa'asalaina o le USP Orlistat RS i le vaifofo masani (µg/mL)
CU = fa'asalaina ole Orlistat ile fa'ata'ita'iga fofo (µg/mL)
F = fua fa'atatau tali e pei ona maua i le Fa'aleaga Siata 2
Ta'iala e talia: Va'ai Fuafuaga Le mama 2.
La'ai le mama 2
Igoa Taimi Taofi Fa'atatau Fa'atatau Tali Tali Fa'atatau Fa'atalia, NMT (%)
Orlistat feso'ota'iga fa'atasi D 0.94 1.0 0.2
Orlistat 1.00 - -
Orlistat mama tatala 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.
• Faiga 5: Tapula'a ole Orlistat Related Compound E
Pa'u: 0.4 N borate solution, fetu'una'i ile pH ole 10.2
Su'esu'e fa'ameamea: vaifofo o-Phthaldehyde (OPA).[Manatua-Afai e le mafai ona maua faapisinisi, e mafai ona saunia le Derivitizing agent e pei o le 1% o le 3-mercaptopropionic acid ma le o-phthaldialdehyde i le 0.4 M borate buffer solution.]
Fofo A: Fa'aliliu le 4.1 g o le sodium acetate trihydrate ma le 40 mg o le ethylenediaminetetraacetic acid (EDTA) i totonu o se fagu volumetric 1-L.Fa'amuta ile 950 mL ole vai, ma fetuutuunai ile 0.1 N sodium hydroxide ile pH ole 7.2.Fa'asusu i le vai i le voluma, fa'aopopo le 2.5 mL o le tetrahydrofuran, ma fa'afefiloi.Filter, ma degas.
Fofo B: Fa'aliliu le 2.7 g o le sodium acetate trihydrate ma le 40 mg o le EDTA i totonu o se fagu volumetric 1-L.Fa'amuta ile 200 mL ole vai, ma fa'afetaui ile 0.1 N sodium hydroxide ile pH ole 7.2.Faaopopo le 800 mL o le acetonitrile, faamama, ma degas.
Vaega feavea'i: Va'ai le laulau fa'alili i lalo.
Taimi (min) Fofo A (%) Fofo 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
Fofo masani: Fa'aliliu se aofa'i fua e tusa ma le 0.2 mg o le USP Orlistat Related compound E RS i totonu o se fagu 20-mL ulu avanoa.Faaopopo le 10 mL ole 4 N sodium hydroxide, ma tapuni le fagu.Fa'amafanafana le fagu i le 100 mo le 1 itula, ona fa'aalili lea i le vevela potu.Su'e le 2 mL o le vaifofo na maua i totonu o se fagu volumetric 50-mL, ma fa'afefe i le vai i le voluma.I le 0.5 mL o lenei vaifofo fa'aopoopo le 2.0 mL o le Buffer ma le 0.5 mL o le Derivatizing agent.
Faʻataʻitaʻiga fofo: Faʻaauau e pei ona faʻatonuina mo le vaifofo masani, ae faʻaaoga le 25 mg o Orlistat e sui ai le 0.2 mg o le USP Orlistat Related Compound E RS.
Faiga fa'akomepiuta
(Va'ai Chromatography <621>, Faiga Fa'atonu.)
Auala: LC
Su'esu'e: Fluorescence 340 nm (fa'afiafiaga);450 nm (emisi)
Koluma
Leoleo: 2.1-mm × 2-cm;50-µm fa'apipi'i L1
Iloiloga: 2.1-mm × 20-cm;afifiina L1
Fuafuaga tafe: 0.5 mL/min
Tele tui: 20 µL
Faiga talafeagai
Fa'ata'ita'iga: Fofo masani
Mana'oga talafeagai
Feso'ota'iga tulaga fa'atusa: NMT 6.0% mo le fa'aputuga fa'atasi o le orlistat E pito i luga
Iloiloga
Faʻataʻitaʻiga: Fofo masani ma Faʻataʻitaʻiga fofo
Faʻatusatusa le pasene o lenei mea le mama i le vaega ole Orlistat na ave:
I'uga = (rU/rS) × (CS/CU) × 100
rU = tali pito i luga mo orlistat e fesoʻotaʻi faʻatasi E i le faʻataʻitaʻiga fofo
rS = tali pito i luga mo USP Orlistat Related Compound E RS i le fofo masani
CS = fa'atonuga o le USP Orlistat Related Compound E RS i le vaifofo masani (mg/mL)
CU = fa'atonuga ole Orlistat ile fa'ata'ita'iga fofo (mg/mL)
Tulaga taliaina
Fa'aleaga tagata ta'ito'atasi: NMT 0.2% ole fa'aputuga fa'atasi ole orlistat E maua.
Aofa'iga o mea leaga: NMT 1.0% o le aofa'i o mea leaga ua maua, o fa'ai'uga mo Fa'asologa 1, 2, 3, 4, ma le 5 ua fa'aopoopoina.
SU'E FA'AMANATU
• Va'aiga Fa'ata'ita'i, Ta'amilosaga Fa'apitoa <781>
Fa'ata'ita'iga vaifofo: 30 mg/mL ile 'ava malosi
Tulaga taliaina: I le va o le -48.0 ma le -51.0, ile 20
• Fuafuaga Suavai, Metotia Ic <921>: NMT 0.2%
FAAOPOOPOGA
• Fa'apipi'i ma Teuina: Fa'asao i pusa tapuni lelei ile va ole 2 ma le 8℃.
• USP Reference Standards <11>
USP Orlistat RS
USP Orlistat Related Compound A RS
USP Orlistat Related Compound B RS
USP Orlistat Related Compound C RS
USP Orlistat Related Compound D RS
USP Orlistat Related Compound E RS
USP35