Orlistat CAS 96829-58-2 API Qhov hnyav Loss Tshuaj 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 nrog (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]-2-oxetanone [96829-58-2].
DEFINITION
Orlistat muaj NLT 98.0% thiab NMT 101.5% ntawm C29H53NO5, xam los ntawm cov dej tsis muaj dej, hnyav-dawb.
IDENTIFICATION
• A. Infrared Absorption <197M>
• B. Lub sij hawm khaws cia ntawm lub ncov loj ntawm cov qauv kev daws teeb meem sib raug rau cov txheej txheem kev daws teeb meem, raws li tau txais hauv Assay.
QHIA
• Cov txheej txheem
[Ceeb Toom-Tsis txhob siv cov yas ntim yas rau kev npaj lossis ntim cov tshuaj hauv qhov kev tshuaj ntsuam no.]
Mobile theem: Acetonitrile, phosphoric acid, thiab dej (860: 0.05: 140)
Kev daws teeb meem: 0.5 mg / mL ntawm USP Orlistat RS nyob rau theem txawb.Txhaj tam sim tom qab kev npaj lossis khaws cia ntawm 5.
Cov tshuaj piv txwv: 0.5 mg / mL ntawm Orlistat nyob rau theem Mobile.Txhaj tam sim tom qab kev npaj lossis khaws cia ntawm 5.
Chromatographic system
(Saib Chromatography <621>, System Suitability.)
Qauv: LC
Detector: UV 195
Kem: 3.9-mm × 15-cm;4-µm ntim L1
Tus nqi ntws: 1.0 mL / min
Kev txhaj tshuaj loj: 20 µL
Qhov system haum
Qauv: Standard tov
Suitability xav tau
Tus txheeb ze tus qauv sib txawv: NMT 2.0%
Kev tsom xam
Qauv: Cov qauv kev daws teeb meem thiab cov qauv kev daws teeb meem
Xam cov feem pua ​​​​ntawm orlistat (C29H53NO5) hauv feem ntawm Orlistat noj:
Result = (rU/rS) × (CS/CU) × 100
rU = ncov teb los ntawm Sample tov
rS = ncov teb los ntawm Standard tov
CS = concentration ntawm USP Orlistat RS nyob rau hauv Standard tov (mg / mL)
CU = concentration ntawm Orlistat nyob rau hauv cov qauv tov (mg / mL)
Kev lees txais cov qauv: 98.0% -101.5% ntawm lub hauv paus tsis muaj dej, hnyav-dawb
IMPURITIES
Inorganic impurities
• Residue ntawm Ignition <281>: NMT 0.1%
• Heavy Metals, Method II <231>: 20 ppm
Organic impurities
• Txheej txheem 1: Kev txwv ntawm Orlistat Related Compound A
Kev daws teeb meem: 0.1 mg / mL ntawm USP Orlistat Related Compound A RS hauv acetone
Cov qauv tshuaj: 50 mg / mL ntawm Orlistat hauv acetone
Chromatographic system
(Saib Chromatography <621>, Thin-Layer Chromatography.)
Mode: TLC
Adsorbent: 0.25-mm txheej ntawm chromatographic silica gel sib tov
Daim ntawv ntim: 10 µL
Tsim cov kuab tshuaj: Toluene thiab ethyl acetate (4: 1)
Kev kuaj pom kev daws teeb meem: Hloov 2.5 g ntawm phosphomolybdic acid thiab 1 g ntawm cerric sulfate rau hauv 100-mL ntim ntim, yaj hauv thiab dilute nrog methanol rau ntim.
Kev tsom xam
Qauv: Cov qauv kev daws teeb meem thiab cov qauv kev daws teeb meem
Tshem lub phaj, thiab cua qhuav kom huv si.Txau lub phaj qhuav nrog Kev Tshawb Fawb, thiab muab lub phaj tso rau hauv qhov cub ntawm 120 rau 30 feeb.
Kev lees txais cov qauv: Txhua qhov chaw thib ob los ntawm cov qauv kev daws teeb meem sib raug rau orlistat ntsig txog qhov sib xyaw A tsis yog khaus ntau dua li qhov chaw sib xws los ntawm Cov Qauv Txheej Txheem (0.2%).
• Txheej txheem 2: Kev txwv ntawm Orlistat Related Compound B
Kev daws teeb meem: 0.025 mg / mL ntawm USP Orlistat Related Compound B RS hauv methylene chloride
Cov qauv tshuaj: 50 mg / mL ntawm Orlistat hauv methylene chloride
Spiked qauv tov: 50 mg / mL ntawm Orlistat hauv Standard tov
Chromatographic system
(Saib Chromatography <621>, System Suitability.)
Qauv: GC
Detector: Nplaim ionization
Kem: 0.32-mm x 30-m fused silica, coated nrog 0.25-µm G27 nyob ruaj khov theem
Kem qhov kub thiab txias: Saib daim ntawv teev qhov kub thiab txias hauv qab no.
Qhov ntsuas kub pib () Qhov kub thiab txias (/min) Qhov Ntsuas Kub Kawg () Tuav Lub Sijhawm ntawm Qhov Kub Kawg (min)
50 4 170 -
170 30 300 30 ib
Kub
Lub cev muaj zog: 270
Tus naj npawb: 280
Carrier gas: Helium
Tus nqi ntws: 30 mL / min
Split ratio: 10: 1
Kev txhaj tshuaj loj: 2 µL
Qhov system haum
Qauv: Standard tov
Suitability xav tau
Tus txheeb ze tus qauv sib txawv: NMT 10.0%
Kev tsom xam
Samples: Sample solution and Spiked sample solution
Xam cov feem pua ​​​​ntawm cov orlistat ntsig txog cov khoom sib txuas B hauv feem ntawm Orlistat noj:
Result = [rU/(rSP rU)] × (CS/CT) × 100
rU = ncov teb ntawm orlistat ntsig txog compound B los ntawm cov qauv tshuaj
rSP = ncov teb ntawm orlistat ntsig txog compound B los ntawm Spiked qauv tov
CS = concentration ntawm USP Orlistat Related Compound B RS nyob rau hauv cov txheej txheem tov (mg / mL)
CT = concentration ntawm Orlistat nyob rau hauv cov tshuaj Spiked qauv (mg / mL)
Kev lees txais cov qauv: NMT 0.05% ntawm orlistat ntsig txog compound B pom.
• Txheej txheem 3
[Ceeb Toom-Tsis txhob siv cov yas ntim yas rau kev npaj lossis ntim cov tshuaj hauv qhov kev tshuaj ntsuam no.]
Mobile theem, Standard solution, thiab Sample solution: Npaj raws li qhia hauv Assay.
Kev daws teeb meem tsim nyog: 10 µg / mL ntawm USP Orlistat RS, 0.1 µg / mL ntawm USP Orlistat Related Compound C RS, thiab 0.25 µg / mL ntawm USP Orlistat Related Compound D RS hauv theem txawb
Chromatographic system
(Saib Chromatography <621>, System Suitability.)
Ua raws li tau hais hauv Assay, tshwj tsis yog rau chromatograph qhov kev daws teeb meem tsim nyog.
Qhov system haum
Qauv: Kev daws teeb meem tsim nyog
Suitability xav tau
Teeb liab-rau-nruas piv: NLT 3 rau orlistat ntsig txog compound C thiab orlistat ntsig txog compound D peaks
Tus txheeb ze tus qauv sib txawv: NMT 10.0% rau lub ncov orlistat
Kev tsom xam
Qauv: Cov qauv kev daws teeb meem thiab cov qauv kev daws teeb meem
Xam cov feem pua ​​​​ntawm txhua qhov impurity nyob rau hauv feem ntawm Orlistat noj:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
rU = ncov teb rau txhua tus neeg impurity los ntawm cov qauv tov
rS = ncov teb ntawm USP Orlistat RS los ntawm Standard tov
CS = concentration ntawm USP Orlistat RS nyob rau hauv Standard tov (mg / mL)
CU = concentration ntawm Orlistat nyob rau hauv cov qauv tov (mg / mL)
F = tus txheeb ze teb qhov tseem ceeb raws li tau muab hauv Impurity Table 1
Cov txheej txheem lees txais: Saib Cov Lus Qhia Tsis Txaus Siab 1.
Impurity Table 1
Lub Sijhawm Relative Retention Time Relative Response Factor Acceptance Criteria, NMT (%)
Formylleucinea 0.10 4.0 0.2
Orlistat muaj feem cuam tshuam C 0.13 33 0.05
Orlistat qhib lub nplhaib epimerb 0.44 1.0 0.2
Orlistat muaj feem xyuam nrog D * 0.90 - xam hauv
Txheej txheem 4
Orlistat qhib lub nplhaib amidec * 0.90 - Muab xam rau hauv
Txheej txheem 4
Orlistat 1.00 Nws.
d-Leucine orlistatd 1.18 1.0 0.2
Tus kheej tsis pom qhov tsis huv - 1.0 0.1
* Coelutes hauv LC system, txiav txim siab siv Txoj Cai 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 los yog enantiomer.
• Txheej txheem 4: Kev txwv ntawm Orlistat Related Compound D
Mobile theem: Methanol thiab dej (83:17)
Cov kev daws teeb meem tsim nyog: 4 mg / mL ntawm USP Orlistat RS thiab 2.4 µg / mL ntawm USP Orlistat Related Compound D RS hauv acetonitrile, feem.
Kev daws teeb meem: 5.0 mg / mL ntawm USP Orlistat RS hauv acetonitrile
Cov qauv tshuaj: 5.0 mg / mL ntawm Orlistat hauv acetonitrile
Chromatographic system
(Saib Chromatography 621, System Suitability.)
Qauv: LC
Ntes: 205nm
Kem: 4.0-mm × 25-cm;5-µm ntim L7
Tus nqi ntws: 0.6 mL / min
Kev txhaj tshuaj loj: 20 µL
Qhov system haum
Qauv: Kev daws teeb meem tsim nyog
Suitability xav tau
Lub teeb liab-rau-nrawm piv: NLT 3 rau orlistat muaj feem xyuam nrog D ncov
Tus txheeb ze tus qauv sib txawv: NMT 10.0% rau lub ncov orlistat
Kev tsom xam
Qauv: Cov qauv kev daws teeb meem thiab cov qauv kev daws teeb meem
Xam cov feem pua ​​​​ntawm txhua qhov impurity nyob rau hauv feem ntawm Orlistat noj:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
rU = ncov teb rau txhua tus neeg impurity los ntawm cov qauv tov
rS = ncov teb rau USP Orlistat RS los ntawm Standard tov
CS = concentration ntawm USP Orlistat RS nyob rau hauv Standard tov (µg/mL)
CU = concentration ntawm Orlistat nyob rau hauv cov qauv tov (µg/mL)
F = tus txheeb ze cov lus teb raws li tau txais hauv Impurity Table 2
Kev lees txais cov qauv: Saib Cov Lus Qhia Tsis Txaus Siab 2.
Impurity Table 2
Lub Sijhawm Relative Retention Time Relative Response Factor Acceptance Criteria, NMT (%)
Orlistat muaj feem xyuam nrog D 0.94 1.0 0.2
Orlistat 1.00 Nws.
Orlistat qhib lub nplhaib amidea 1.25 4.3 0.1
N-Formyl-l-leucine (S)-1-[(2S,3S)-2-hydroxy-3-[1-phenyl-R-ethylcarbomoyl]nonyl]-dodecyl ester.
• Txheej txheem 5: Kev txwv ntawm Orlistat Related Compound E
Buffer: 0.4 N borate tov, kho rau pH ntawm 10.2
Derivitizing tus neeg sawv cev: o-Phthaldehyde (OPA) tov.[Ceeb toom-Yog tias tsis tuaj yeem tau txais kev lag luam, tus neeg sawv cev Derivitizing tuaj yeem npaj tau li 1% txhua ntawm 3-mercaptopropionic acid thiab o-phthaldialdehyde hauv 0.4 M borate buffer tov.]
Kev daws A: Hloov 4.1 g ntawm sodium acetate trihydrate thiab 40 mg ntawm ethylenediaminetetraacetic acid (EDTA) rau hauv 1-L ntim ntim.Dissolve hauv 950 mL dej, thiab kho nrog 0.1 N sodium hydroxide mus rau pH ntawm 7.2.Dilute nrog dej rau ntim, ntxiv 2.5 mL ntawm tetrahydrofuran, thiab sib tov.Lim, thiab degas.
Kev daws B: Hloov 2.7 g ntawm sodium acetate trihydrate thiab 40 mg ntawm EDTA rau hauv 1-L volumetric hwj.Dissolve hauv 200 mL dej, thiab kho nrog 0.1 N sodium hydroxide mus rau pH ntawm 7.2.Ntxiv 800 mL ntawm acetonitrile, lim, thiab degas.
Mobile theem: Saib lub gradient table hauv qab no.
Sijhawm (min) Kev daws A (%) Kev daws B (%)
0 96.7 3.3
20 6040
24 0100
380 100 ib
38 96.7 3.3
45 96.7 3.3
Kev daws teeb meem: Hloov qhov hnyav txog li 0.2 mg ntawm USP Orlistat Related compound E RS rau hauv 20-mL taub hau-qhov vial.Ntxiv 10 mL ntawm 4 N sodium hydroxide, thiab kaw lub vial.Tshav kub lub vial rau 100 rau 1 h, ces cia kom txias rau chav tsev kub.Hloov 2 mL ntawm cov kev daws teeb meem rau hauv 50-mL ntim ntim, thiab dilute nrog dej rau ntim.Rau 0.5 mL ntawm cov tshuaj no ntxiv 2.0 mL ntawm Buffer thiab 0.5 mL ntawm Derivatizing tus neeg sawv cev.
Cov qauv kev daws teeb meem: Ua raws li cov lus qhia rau Cov Qauv Txheej Txheem, tab sis siv 25 mg ntawm Orlistat los hloov 0.2 mg ntawm USP Orlistat Related Compound E RS.
Chromatographic system
(Saib Chromatography <621>, System Suitability.)
Qauv: LC
Ntes: Fluorescence 340 nm (excitation);450nm (emission)
Cov kab
Guard: 2.1-mm × 2-cm;50-µm ntim L1
Analytical: 2.1-mm × 20-cm;ntim L1
Tus nqi ntws: 0.5 mL / min
Kev txhaj tshuaj loj: 20 µL
Qhov system haum
Qauv: Standard tov
Suitability xav tau
Tus txheeb ze tus qauv sib txawv: NMT 6.0% rau orlistat muaj feem xyuam nrog E ncov
Kev tsom xam
Qauv: Cov qauv kev daws teeb meem thiab cov qauv kev daws teeb meem
Xam qhov feem pua ​​​​ntawm cov impurity no hauv feem ntawm Orlistat noj:
Result = (rU/rS) × (CS/CU) × 100
rU = ncov teb rau orlistat ntsig txog compound E hauv cov qauv tshuaj
rS = ncov teb rau USP Orlistat Related Compound E RS nyob rau hauv tus txheej txheem tov
CS = concentration ntawm USP Orlistat Related Compound E RS nyob rau hauv Standard tov (mg / mL)
CU = concentration ntawm Orlistat nyob rau hauv cov qauv tov (mg / mL)
Kev lees txais
Ib tug neeg impurity: NMT 0.2% ntawm orlistat ntsig txog compound E pom.
Tag nrho impurities: NMT 1.0% ntawm tag nrho cov impurities pom, cov txiaj ntsig rau Cov Txheej Txheem 1, 2, 3, 4, thiab 5 tau ntxiv.
TSEEM CEEB
• Kev sib hloov kho qhov muag, Kev sib hloov tshwj xeeb <781>
Piv txwv li: 30 mg / mL nyob rau hauv lub cev qhuav dej cawv
Kev lees txais: Ntawm -48.0 thiab -51.0, ntawm 20
• Kev Txiav Txim Dej, Txoj Kev Ic <921>: NMT 0.2%
TSEEM CEEB
• Ntim thiab Cia: Khaws rau hauv cov thawv kaw kom zoo ntawm 2 txog 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