I-Orlistat CAS 96829-58-2 API Ukunciphisa Ubunzima beziyobisi Ukucoceka kweziyobisi 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 kunye (3S, 4S) -3-hexyl-4-[(2S) -2-hydroxytridecyl] -2-oxetanone [96829-58-2].
INGCACISO
I-Orlistat iqulethe i-NLT 98.0% kunye ne-NMT 101.5% ye-C29H53NO5, ibalwe kwisiseko se-anhydrous, i-solvent-free basis.
UKUCHAZA
• A. I-Infrared Absorption <197M>
• B. Ixesha lokugcinwa kwencopho enkulu yesisombululo seSampuli sihambelana nesoMgangatho wesisombululo, njengoko sifunyenwe kwi-Assay.
UVAVANYO
• Inkqubo
[Qaphela-Kuphephe ukusetyenziswa kweeflaski zeplastiki ukulungiselela okanye ukuqulathwa kwaso nasiphi na isisombululo kolu hlalutyo.]
Isigaba esiphathwayo: I-Acetonitrile, i-phosphoric acid, kunye namanzi (860: 0.05: 140)
Isisombululo esisemgangathweni: 0.5 mg / mL ye-USP Orlistat RS kwisigaba seMobile.Tofa ngokukhawuleza emva kokulungiselela okanye ugcine ngo-5.
Isisombululo sesampuli: 0.5 mg / mL ye-Orlistat kwisigaba se-Mobile.Tofa ngokukhawuleza emva kokulungiselela okanye ugcine ngo-5.
Inkqubo yeChromatographic
(Jonga iChromatography <621>, Ukufaneleka kweNkqubo.)
Indlela: LC
Umtshina: UV 195
Ikholamu: 3.9-mm × 15-cm;4-µm ukupakisha i-L1
Izinga lokuhamba: 1.0 mL / min
Ubungakanani betofu: 20 µL
Ukufaneleka kwenkqubo
Isampulu: Isisombululo esisemgangathweni
Iimfuno zokufaneleka
Ukutenxa komgangatho ozalanayo: NMT 2.0%
Uhlalutyo
Iisampulu: Isisombululo esisemgangathweni kunye nesisombululo seSampuli
Bala ipesenti ye-orlistat (C29H53NO5) kwisahlulo se-Orlistat ethathiweyo:
Isiphumo = (rU/rS) × (CS/CU) × 100
rU = impendulo ephezulu evela kwiSampuli yesisombululo
rS = impendulo ephezulu evela kwisisombululo esiPhakathi
CS = ukuxinwa kwe-USP Orlistat RS kwisisombululo esiPhakathi (mg / mL)
I-CU = i-concentration ye-Orlistat kwisisombululo seSampule (mg / mL)
Indlela yokwamkela: 98.0% -101.5% kwi-anhydrous, isiseko se-solvent-free
UBUNGCOLA
Ukungcola Kwezinto Eziphilayo
• Intsalela ekuZisweni <281>: NMT 0.1%
• Iintsimbi ezinzima, iNdlela II <231>: 20 ppm
Ukungcola Okuphilayo
• Inkqubo 1: Umda we-Orlistat eNxulumene neCompound A
Isisombululo esisemgangathweni: 0.1 mg / mL ye-USP Orlistat eNxulumene neCompound A RS kwi-acetone
Isisombululo sesampuli: 50 mg / mL ye-Orlistat kwi-acetone
Inkqubo yeChromatographic
(Jonga iChromatography <621>, iChromatography eThin-Layer.)
Indlela: TLC
I-Adsorbent: 0.25-mm umaleko we-chromatographic umxube we-silica gel
Umthamo wosetyenziso: 10 µL
Ukuphuhlisa inkqubo yokunyibilikisa: Toluene kunye ne-ethyl acetate (4:1)
Isisombululo sokufumanisa: Dlulisa i-2.5 g ye-phosphomolybdic acid kunye ne-1 g ye-cerric sulfate kwi-flask ye-volumetric ye-100-mL, udibanise kwaye udibanise nge-methanol kwivolumu.
Uhlalutyo
Iisampulu: Isisombululo esisemgangathweni kunye nesisombululo seSampuli
Susa ipleyiti, kwaye womise ngomoya ngokucokisekileyo.Gcoba ipleyiti eyomileyo kunye nesisombululo se-Detection, kwaye ubeke isitya kwi-oven kwi-120 kwi-30 min.
Iinqobo zokwamkelwa: Nayiphi na indawo yesibini kwisisombululo seSampuli esihambelana ne-orlistat ehambelana ne-compound A ayinamandla ngaphezu kwendawo ehambelana nayo kwisisombululo esiPhakathi (0.2%).
• Inkqubo yesi-2: Umda we-Orlistat eNxulumene neCompound B
Isisombululo esisemgangathweni: 0.025 mg / mL ye-USP Orlistat eNxulumene neCompound B RS kwi-methylene chloride
Isisombululo sesampuli: 50 mg / mL ye-Orlistat kwi-methylene chloride
Isisombululo sesampula se-Spiked: 50 mg / mL ye-Orlistat kwisisombululo esisemgangathweni
Inkqubo yeChromatographic
(Jonga iChromatography <621>, Ukufaneleka kweNkqubo.)
Indlela: GC
Umtshina: Iionization yomlilo
Ikholamu: 0.32-mm x 30-m silica edityanisiweyo, iqatywe nge-0.25-µm G27 isigaba sokumisa
Ubushushu bekholamu: Bona itheyibhile yenkqubo yobushushu engezantsi.
Iqondo lobushushu lokuqala () Irempu yoBubushushu (/min) iBuzulu yokuGqibela () Ukubamba ixesha kuBubushushu bokugqibela (umzuzu)
50 4 170 -
170 30 300 30
Ubushushu
Isitofu: 270
Umtshina: 280
Irhasi yokuthwala: iHelium
Izinga lokuhamba: 30 mL / min
Umlinganiselo wokwahlula: 10:1
Ubungakanani bokutofa: 2 µL
Ukufaneleka kwenkqubo
Isampulu: Isisombululo esisemgangathweni
Iimfuno zokufaneleka
Ukutenxa umgangatho ozalanayo: NMT 10.0%
Uhlalutyo
Iisampulu: Isampuli yesisombululo kunye nesisombululo sesampulu eSpiked
Bala ipesenti ye-orlistat enxulumene nekhompawundi B kwinxalenye ye-Orlistat ethathiweyo:
Isiphumo = [rU/(rSP rU)] × (CS/CT) × 100
I-rU = impendulo ephezulu ye-orlistat ehambelana ne-compound B kwisisombululo seSampule
I-rSP = impendulo ephezulu ye-orlistat ehambelana nekhompawundi B kwisisombululo sesampuli se-Spiked
I-CS = i-concentration ye-USP ye-Orlistat eNxulumene neCompound B RS kwisisombululo soMgangatho (mg / mL)
I-CT = i-concentration ye-Orlistat kwisisombululo sesampuli ye-Spiked (mg / mL)
Indlela yolwamkelo: I-NMT 0.05% ye-orlistat enxulumene nekhompawundi B ifunyenwe.
• Inkqubo yesi-3
[Qaphela-Kuphephe ukusetyenziswa kweeflaski zeplastiki ukulungiselela okanye ukuqulathwa kwaso nasiphi na isisombululo kolu hlalutyo.]
Isigaba seselula, isisombululo esiPhakathi, kunye nesisombululo seSampuli: Lungiselela njengoko kuyalelwe kwi-Assay.
Isisombululo sokufaneleka kwenkqubo: 10 µg/mL ye-USP Orlistat RS, 0.1 µg/mL ye-USP Orlistat eNxulumene neCompound C RS, kunye ne-0.25 µg/mL ye-USP Orlistat eNxulumene neCompound D RS kwisigaba seMobile
Inkqubo yeChromatographic
(Jonga iChromatography <621>, Ukufaneleka kweNkqubo.)
Qhubeka njengoko kuyalelwe kwi-Assay, ngaphandle kwechromatograph isisombululo sokufaneleka kweNkqubo.
Ukufaneleka kwenkqubo
Isampulu: Isisombululo sokufaneleka kwenkqubo
Iimfuno zokufaneleka
Umlinganiselo we-Signal-to-noise ratio: I-NLT 3 ye-orlistat enxulumene ne-C kunye ne-orlistat ehambelana ne-compound D iincopho
Ukutenxa komgangatho ozalanayo: NMT 10.0% yencopho ye-orlistat
Uhlalutyo
Iisampulu: Isisombululo esisemgangathweni kunye nesisombululo seSampuli
Bala ipesenti yokungcola ngakunye kwisahlulo seOrlistat esithathiweyo:
Isiphumo = (rU/rS) × (CS/CU) × (1/F) × 100
I-rU = impendulo ephezulu yokungcola komntu ngamnye kwisisombululo seSampuli
rS = impendulo ephezulu ye-USP Orlistat RS kwisisombululo esiPhakathi
CS = ukuxinwa kwe-USP Orlistat RS kwisisombululo esiPhakathi (mg / mL)
I-CU = i-concentration ye-Orlistat kwisisombululo seSampule (mg / mL)
F = isalamane sempendulo njengoko inikwe kwiTheyibhile yoku-1 yokungacoceki
Indlela yokwamkela: Jonga iTheyibhile yoku-1 yoKungacoceki.
Itheyibhile yokungcola 1
Igama lokuGcina iSinxulumano Ixesha leMpendulo enxulumeneyo Umgaqo wokwamkelwa kweFactor, NMT (%)
Formylleucinea 0.10 4.0 0.2
Ikhompawundi enxulumene ne-Orlistat C 0.13 33 0.05
Orlistat vula ring epimerb 0.44 1.0 0.2
I-Orlistat enxulumene nekhompawundi D * 0.90 - Kubalwa kuyo
Inkqubo yesi-4
I-Orlistat ring ring amidec * 0.90 - Kubalwa kuyo
Inkqubo yesi-4
I-Orlistat 1.00 - -
d-Leucine orlistatd 1.18 1.0 0.2
Ukungcola komntu ngamnye okungachazwanga - 1.0 0.1
* Ii-Coelutes kule nkqubo ye-LC, emiselwe ukusebenzisa iNkqubo yesi-4.
a 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 okanye enantiomer.
• Inkqubo yesi-4: Umda we-Orlistat eNxulumene neCompound D
Inqanaba leselula: Methanol namanzi (83:17)
Isisombululo sokufaneleka kwenkqubo: 4 mg / mL ye-USP Orlistat RS kunye ne-2.4 µg / mL ye-USP Orlistat eNxulumene neCompound D RS kwi-acetonitrile, ngokulandelanayo
Isisombululo esisemgangathweni: 5.0 mg / mL ye-USP Orlistat RS kwi-acetonitrile
Isisombululo sesampuli: 5.0 mg / mL ye-Orlistat kwi-acetonitrile
Inkqubo yeChromatographic
(Jonga iChromatography 621, Ukufaneleka kweNkqubo.)
Indlela: LC
Umtshina: 205 nm
Ikholamu: 4.0-mm × 25-cm;5-µm ukupakisha i-L7
Izinga lokuhamba: 0.6 mL / min
Ubungakanani betofu: 20 µL
Ukufaneleka kwenkqubo
Isampulu: Isisombululo sokufaneleka kwenkqubo
Iimfuno zokufaneleka
Umlinganiselo we-Signal-to-noise: NLT 3 ye-orlistat enxulumene ne-compound D peak
Ukutenxa komgangatho ozalanayo: NMT 10.0% yencopho ye-orlistat
Uhlalutyo
Iisampulu: Isisombululo esisemgangathweni kunye nesisombululo seSampuli
Bala ipesenti yokungcola ngakunye kwisahlulo seOrlistat esithathiweyo:
Isiphumo = (rU/rS) × (CS/CU) × (1/F) × 100
I-rU = impendulo ephezulu yokungcola komntu ngamnye kwisisombululo seSampuli
rS = impendulo ephezulu ye-USP Orlistat RS kwisisombululo esiPhakathi
CS = ukuxinwa kwe-USP Orlistat RS kwisisombululo esiPhakathi (µg/mL)
I-CU = i-concentration ye-Orlistat kwisisombululo seSampule (µg/mL)
F = isalamane sokuphendula into njengoko ifunyenwe kwiThebhile ye-2 yokungcola
Indlela yokwamkela: Jonga iTheyibhile yesi-2 yoKungacoceki.
Itheyibhile yokungcola 2
Igama lokuGcina iSinxulumano Ixesha leMpendulo enxulumeneyo Umgaqo wokwamkelwa kweFactor, NMT (%)
Ikhompawundi enxulumene ne-Orlistat D 0.94 1.0 0.2
I-Orlistat 1.00 - -
I-Orlistat vula i-ring 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.
• Inkqubo yesi-5: Umda we-Orlistat eNxulumene neCompound E
Isithinteli: 0.4 isisombululo se-N borate, esilungelelaniswe kwi-pH ye-10.2
I-arhente yokuphuma: isisombululo se-o-Phthaldehyde (OPA).[Qaphela-Ukuba awukwazi ukufumana urhwebo, i-arhente ye-Derivitizing ingalungiswa njenge-1% nganye ye-3-mercaptopropionic acid kunye ne-o-phthaldialdehyde kwi-0.4 M isisombululo se-borate buffer.]
Isisombululo A: Dlulisa i-4.1 g ye-sodium acetate trihydrate kunye ne-40 mg ye-ethylenediaminetetraacetic acid (EDTA) kwi-flask ye-volumetric ye-1-L.Dissolve kwi-950 mL yamanzi, kwaye ulungelelanise ne-0.1 N sodium hydroxide kwi-pH ye-7.2.Nciphisa ngamanzi kumthamo, yongeza i-2.5 mL ye-tetrahydrofuran, kwaye udibanise.Isihluzo, kunye ne-degas.
Isisombululo B: Dlulisa i-2.7 g ye-sodium acetate trihydrate kunye ne-40 mg ye-EDTA kwi-flask ye-volumetric 1-L.Dissolve kwi-200 mL yamanzi, kwaye ulungelelanise ne-0.1 N sodium hydroxide kwi-pH ye-7.2.Yongeza i-800 mL ye-acetonitrile, isihluzo, kunye ne-degas.
Isigaba esiphathwayo: Bona itheyibhile yodidi olungezantsi.
Ixesha (min) Isisombululo A (%) Isisombululo 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
Isisombululo esisemgangathweni: Dlulisa ubungakanani obulinganisiweyo malunga ne-0.2 mg ye-USP ye-Orlistat eNxulumene ne-E RS kwi-vial ye-20-mL yentloko.Yongeza i-10 mL ye-4 N sodium hydroxide, kwaye uvale i-vial.Fudumeza i-vial kwi-100 nge-1 h, uze uvumele ukupholisa kwiqondo lokushisa.Dlulisa i-2 mL yesisombululo esisiphumo kwi-flask ye-volumetric 50-mL, kwaye uhlambulule ngamanzi ukuya kumthamo.Ukuya kwi-0.5 mL yesi sisombululo yongeza i-2.0 mL ye-Buffer kunye ne-0.5 mL ye-agent ye-Derivatizing.
Isisombululo sesampuli: Qhubeka njengoko uqondiswe kwisisombululo esiPhakathi, kodwa endaweni yoko sebenzisa i-25 mg ye-Orlistat ukuba ithathe indawo ye-0.2 mg ye-USP Orlistat eNxulumene neCompound E RS.
Inkqubo yeChromatographic
(Jonga iChromatography <621>, Ukufaneleka kweNkqubo.)
Indlela: LC
Umtshina: Fluorescence 340 nm (uchulumanco);450 nm (ukukhutshwa)
Imihlathi
Umlindi: 2.1-mm × 2-cm;50-µm ukupakisha i-L1
Uhlalutyo: 2.1-mm × 20-cm;ukupakisha L1
Izinga lokuhamba: 0.5 mL / min
Ubungakanani betofu: 20 µL
Ukufaneleka kwenkqubo
Isampulu: Isisombululo esisemgangathweni
Iimfuno zokufaneleka
Ukutenxa umgangatho ozalanayo: I-NMT 6.0% ye-orlistat enxulumene nekhompawundi E incopho
Uhlalutyo
Iisampulu: Isisombululo esisemgangathweni kunye nesisombululo seSampuli
Bala ipesenti yolu kungcola kwisahlulo se-Orlistat esithathiweyo:
Isiphumo = (rU/rS) × (CS/CU) × 100
I-rU = impendulo ephezulu ye-orlistat ehambelana ne-compound E kwisisombululo seSampuli
rS = impendulo ephezulu ye-USP Orlistat eNxulumene neCompound E RS kwisisombululo soMgangatho
CS = ukuxinwa kwe-USP Orlistat eNxulumene neCompound E RS kwisisombululo esiPhakathi (mg / mL)
I-CU = i-concentration ye-Orlistat kwisisombululo seSampule (mg / mL)
Iinqobo zokwamkelwa
Ukungacoceki komntu: I-NMT 0.2% ye-orlistat enxulumene nekhompawundi E ifunyenwe.
Ubumdaka bubonke: I-NMT 1.0% yobumdaka bubonke ifunyenwe, iziphumo zeNkqubo 1, 2, 3, 4, no-5 zongezwa.
IIMVAVANYO EZITHILE
• Ukujikeleza kwe-Optical, Ukujikeleza ngokuthe ngqo <781>
Isisombululo sesampuli: 30 mg / mL kwi-alcohol dehydrated
Iikhrayitheriya zokumkela: Phakathi kwe-48.0 kunye ne-51.0, kwi-20
• Ukumiselwa kwaManzi, iNdlela ye-Ic <921>: NMT 0.2%
IIMFUNO EZONGEZELELWEYO
• Ukupakishwa kunye noGcino: Londoloza kwizikhongozeli ezivalwe kakuhle phakathi kwe-2 kunye ne-8℃.
• IMigangatho yeReferensi ye-USP <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