Orlistat CAS 96829-58-2 API Isọdiwọn Pipadanu Oogun Mimọ 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 pẹlu (3S,4S) -3-hexyl-4-[(2S) -2-hydroxytridecyl]-2-oxetanone [96829-58-2].
ITUMO
Orlistat ni NLT 98.0% ati NMT 101.5% ti C29H53NO5, ṣe iṣiro lori ipilẹ anhydrous, ipilẹ ti ko ni epo.
Ìdámọ̀
• A. Gbigba infurarẹẹdi <197M>
• B. Awọn akoko idaduro ti awọn pataki tente oke ti awọn Ayẹwo ojutu ni ibamu si awọn ti Standard ojutu, bi gba ninu awọn Assay.
ASAY
• Ilana
[Akiyesi-Yago fun lilo awọn apọn ṣiṣu fun igbaradi tabi idimu eyikeyi ojutu ni itupalẹ yii.]
Ipele alagbeeka: Acetonitrile, phosphoric acid, ati omi (860: 0.05: 140)
Ojutu boṣewa: 0.5 mg/mL ti USP Orlistat RS ni apakan Alagbeka.Abẹrẹ lẹsẹkẹsẹ lẹhin igbaradi tabi tọju ni 5.
Ojutu ayẹwo: 0.5 mg/mL ti Orlistat ni apakan Alagbeka.Abẹrẹ lẹsẹkẹsẹ lẹhin igbaradi tabi tọju ni 5.
Eto Chromatographic
(Wo Chromatography <621>, Ibamu Eto.)
Ipo: LC
Awari: UV 195
Ọwọn: 3.9-mm × 15-cm;4-µm iṣakojọpọ L1
Oṣuwọn sisan: 1.0 milimita / min
Iwọn abẹrẹ: 20µL
Ibamu eto
Apeere: Standard ojutu
Awọn ibeere ibamu
Iyatọ boṣewa ibatan: NMT 2.0%
Onínọmbà
Awọn apẹẹrẹ: Ojutu boṣewa ati ojutu Ayẹwo
Ṣe iṣiro ipin ogorun orlistat (C29H53NO5) ni apakan ti Orlistat ti o mu:
Esi = (rU/rS) × (CS/CU) × 100
rU = idahun ti o ga julọ lati inu ojutu Ayẹwo
rS = idahun ti o ga julọ lati ojutu Standard
CS = ifọkansi ti USP Orlistat RS ni ojutu Standard (mg/mL)
CU = ifọkansi ti Orlistat ninu ojutu Ayẹwo (mg/mL)
Awọn ibeere gbigba: 98.0% -101.5% lori ipilẹ anhydrous, ipilẹ ti ko ni epo
ALÁÌṢẸ́
Awọn Egbin Aiṣedeede
Aloku lori Iginisonu <281>: NMT 0.1%
• Awọn irin Heavy, Ọna II <231>: 20 ppm
Organic impurities
• Ilana 1: Idiwọn Orlistat Compound Jẹmọ A
Ojutu boṣewa: 0.1 mg/mL ti USP Orlistat Compound Jẹmọ A RS ni acetone
Ojutu ayẹwo: 50 mg / mL ti Orlistat ni acetone
Eto Chromatographic
(Wo Chromatography <621>, Kromatography Tinrin.)
Ipo: TLC
Adsorbent: 0.25-mm Layer ti chromatographic silica gel mix
Iwọn ohun elo: 10 µL
Idagbasoke eto epo: Toluene ati ethyl acetate (4: 1)
Ojutu wiwa: Gbigbe 2.5 g ti phosphomolybdic acid ati 1 g cerric sulfate sinu 100-mL volumetric flask, tu sinu ati dilute pẹlu kẹmika si iwọn didun.
Onínọmbà
Awọn apẹẹrẹ: Ojutu boṣewa ati ojutu Ayẹwo
Yọ awo naa kuro, ki o si gbẹ ni afẹfẹ daradara.Sokiri awo ti o gbẹ pẹlu ojutu Iwari, ki o si gbe awo naa sinu adiro ni 120 fun awọn iṣẹju 30.
Awọn ibeere gbigba: Eyikeyi aaye keji lati ojutu Ayẹwo ti o baamu si orlistat ti o ni ibatan agbo A ko ni iwọn diẹ sii ju aaye ti o baamu lati ojutu Standard (0.2%).
• Ilana 2: Idiwọn Orlistat Compound Jẹmọ B
Ojutu boṣewa: 0.025 mg/mL ti USP Orlistat Compound Jẹmọ B RS ni methylene kiloraidi
Ojutu ayẹwo: 50 mg/mL ti Orlistat ni methylene kiloraidi
Ojutu ayẹwo spked: 50 mg/mL ti Orlistat ni ojutu Standard
Eto Chromatographic
(Wo Chromatography <621>, Ibamu Eto.)
Ipo: GC
Oluwadi: ina ionization
Ọwọn: 0.32-mm x 30-m yanrin ti a dapọ, ti a bo pẹlu ipele iduro 0.25-µm G27
Iwọn otutu iwe: Wo tabili eto iwọn otutu ni isalẹ.
Iwọn otutu akọkọ () Iwọn otutu (/ min) Iwọn otutu ikẹhin () Akoko idaduro ni Iwọn otutu Ipari (min)
50 4 170 -
170 30 300 30
Iwọn otutu
Abẹrẹ: 270
Oluwadi: 280
Gaasi ti ngbe: Helium
Oṣuwọn sisan: 30 milimita / min
Pipin ipin: 10:1
Iwọn abẹrẹ: 2µL
Ibamu eto
Apeere: Standard ojutu
Awọn ibeere ibamu
Iyatọ boṣewa ibatan: NMT 10.0%
Onínọmbà
Awọn apẹẹrẹ: Ojutu ayẹwo ati ojutu ayẹwo Spiked
Ṣe iṣiro ipin ti orlistat ti o ni ibatan yellow B ni apakan ti Orlistat ti o mu:
Esi = [rU/(rSP rU)] × (CS/CT) × 100
rU = esi tente oke ti orlistat ti o ni ibatan agbo B lati inu ojutu Ayẹwo
rSP = esi ti o ga julọ ti orlistat ti o ni ibatan akojọpọ B lati inu ojutu ayẹwo Spiked
CS = ifọkansi ti USP Orlistat Compound Jẹmọ B RS ni ojutu Standard (mg/mL)
CT = ifọkansi ti Orlistat ninu ojutu ayẹwo Spiked (mg/mL)
Awọn ibeere gbigba: NMT 0.05% ti orlistat ti o ni ibatan yellow B ti wa.
• Ilana 3
[Akiyesi-Yago fun lilo awọn apọn ṣiṣu fun igbaradi tabi idimu eyikeyi ojutu ni itupalẹ yii.]
Alakoso Alagbeka, Ojutu Standard, ati Ojutu Ayẹwo: Mura silẹ bi a ti ṣe itọsọna ni Assay.
Ojutu ibaamu eto: 10 µg/mL ti USP Orlistat RS, 0.1 µg/mL ti USP Orlistat Compound Jẹmọ C RS, ati 0.25 µg/mL ti USP Orlistat Compound D RS ni apakan Alagbeka
Eto Chromatographic
(Wo Chromatography <621>, Ibamu Eto.)
Tẹsiwaju bi a ti ṣe itọsọna rẹ ni Assay, ayafi si chromatograph ojutu ibaramu Eto.
Ibamu eto
Apeere: Eto ibamu ojutu
Awọn ibeere ibamu
Ipin ifihan agbara-si-ariwo: NLT 3 fun orlistat ti o ni ibatan agbo C ati orlistat ti o ni ibatan D awọn oke
Iyatọ boṣewa ibatan: NMT 10.0% fun oke orlistat
Onínọmbà
Awọn apẹẹrẹ: Ojutu boṣewa ati ojutu Ayẹwo
Ṣe iṣiro ipin ogorun aimọ kọọkan ni apakan ti Orlistat ti o mu:
Esi = (rU/rS) × (CS/CU) × (1/F) × 100
rU = idahun ti o ga julọ fun aimọ kọọkan lati inu ojutu Ayẹwo
rS = esi ti o ga julọ ti USP Orlistat RS lati ojutu Standard
CS = ifọkansi ti USP Orlistat RS ni ojutu Standard (mg/mL)
CU = ifọkansi ti Orlistat ninu ojutu Ayẹwo (mg/mL)
F = ifosiwewe idahun ojulumo bi a ti fun ni Tabili Aimọ 1
Awọn ilana gbigba: Wo Tabili Aimọ 1.
Tabili àìmọ́ 1
Orukọ Aago Idaduro Ojulumo Awọn Ilana Gbigba Idahun Ibaṣepọ, NMT (%)
Formylleucinea 0.10 4.0 0.2
Orlistat ti o ni ibatan C 0.13 33 0.05
Orlistat ṣiṣi oruka epimerb 0.44 1.0 0.2
Orlistat jẹmọ yellow D * 0.90 - Iṣiro ni
Ilana 4
Orlistat ṣiṣi oruka amidec * 0.90 - Iṣiro sinu
Ilana 4
Orlistat 1.00 - -
d-Leucine orlistatd 1.18 1.0 0.2
Olukuluku aimọ aimọ - 1.0 0.1
* Coelutes ninu eto LC yii, pinnu nipa lilo Ilana 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 tabi enantiomer.
• Ilana 4: Ifilelẹ ti Orlistat Compound Jẹmọ D
Ipele alagbeka: kẹmika ati omi (83:17)
Ojutu ibaamu eto: 4 mg/mL ti USP Orlistat RS ati 2.4 µg/mL ti USP Orlistat Compound Jẹmọ D RS ni acetonitrile, lẹsẹsẹ
Ojutu boṣewa: 5.0 mg/mL ti USP Orlistat RS ni acetonitrile
Ojutu ayẹwo: 5.0 mg/mL ti Orlistat ni acetonitrile
Eto Chromatographic
(Wo Chromatography 621, Ibamu Eto.)
Ipo: LC
Oluwadi: 205 nm
Ọwọn: 4.0-mm × 25-cm;5-µm iṣakojọpọ L7
Oṣuwọn sisan: 0.6 milimita / min
Iwọn abẹrẹ: 20µL
Ibamu eto
Apeere: Eto ibamu ojutu
Awọn ibeere ibamu
Ipin ifihan agbara-si-ariwo: NLT 3 fun idapọ ti o jọmọ orlistat D tente oke
Iyatọ boṣewa ibatan: NMT 10.0% fun oke orlistat
Onínọmbà
Awọn apẹẹrẹ: Ojutu boṣewa ati ojutu Ayẹwo
Ṣe iṣiro ipin ogorun aimọ kọọkan ni apakan ti Orlistat ti o mu:
Esi = (rU/rS) × (CS/CU) × (1/F) × 100
rU = idahun ti o ga julọ fun aimọ kọọkan lati inu ojutu Ayẹwo
rS = idahun ti o ga julọ fun USP Orlistat RS lati ojutu Standard
CS = ifọkansi ti USP Orlistat RS ni ojutu Standard (µg/ml)
CU = ifọkansi ti Orlistat ninu ojutu Ayẹwo (µg/ml)
F = ifosiwewe idahun ojulumo bi a ti gba ni Tabili Iwa-igbẹ 2
Ilana gbigba: Wo Tabili Aimọ 2.
Tabili àìmọ́ 2
Orukọ Aago Idaduro Ojulumo Awọn Ilana Gbigba Idahun Ibaṣepọ, NMT (%)
Orlistat ti o ni ibatan D 0.94 1.0 0.2
Orlistat 1.00 - -
Orlistat ṣiṣi oruka 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.
• Ilana 5: Idiwọn Orlistat Compound Jẹmọ E
Idaduro: 0.4 N ojutu borate, ṣatunṣe si pH ti 10.2
Aṣoju itọka: o-Phthaldehyde (OPA) ojutu.[Akiyesi-Ti o ko ba le gba ni iṣowo, aṣoju Derivitizing le ṣe imurasilẹ bi 1% kọọkan ti 3-mercaptopropionic acid ati o-phthaldialdehyde ni 0.4M borate saarin ojutu.]
Solusan A: Gbigbe 4.1 g ti sodium acetate trihydrate ati 40 mg ti ethylenediaminetetraacetic acid (EDTA) sinu 1-L volumetric flask.Tu ni 950 milimita ti omi, ati ṣatunṣe pẹlu 0.1 N sodium hydroxide si pH ti 7.2.Dilute pẹlu omi si iwọn didun, fi 2.5 milimita ti tetrahydrofuran kun, ki o si dapọ.Àlẹmọ, ati degas.
Solusan B: Gbigbe 2.7 g ti sodium acetate trihydrate ati 40 miligiramu ti EDTA sinu ọpọn iwọn didun 1-L.Tu ni 200 milimita ti omi, ati ṣatunṣe pẹlu 0.1 N sodium hydroxide si pH ti 7.2.Fi 800 milimita ti acetonitrile, àlẹmọ, ati degas kun.
Alakoso alagbeka: Wo tabili gradient ni isalẹ.
Akoko (min) Solusan A (%) Solusan B (%)
096.7 3.3
20 60 40
240 100
38 0100
38 96.7 3.3
45 96.7 3.3
Ojutu boṣewa: Gbe opoiye ti o ni iwuwo ti o to 0.2 miligiramu ti USP Orlistat Jẹmọ yellow E RS sinu vial-aaye ori 20-mL.Fi milimita 10 ti 4 N sodium hydroxide kun, ki o si tii vial naa.Ooru vial si 100 fun wakati 1, lẹhinna gba laaye lati dara si iwọn otutu yara.Gbigbe 2 milimita ti ojutu ti o yọrisi sinu ọpọn iwọn didun 50-mL, ki o si dilute pẹlu omi si iwọn didun.Si 0.5 milimita ti ojutu yii ṣafikun 2.0 milimita ti Buffer ati 0.5 milimita ti oluranlowo Derivatizing.
Ojutu Ayẹwo: Tẹsiwaju bi a ti ṣe itọsọna fun ojutu Standard, ṣugbọn dipo lo 25 miligiramu ti Orlistat lati rọpo 0.2 mg ti USP Orlistat Related Compound E RS.
Eto Chromatographic
(Wo Chromatography <621>, Ibamu Eto.)
Ipo: LC
Oluwari: Fluorescence 340 nm (igbega);450 nm (ijadejade)
Awọn ọwọn
Oluso: 2.1-mm × 2-cm;50-µm iṣakojọpọ L1
Itupalẹ: 2.1-mm × 20-cm;iṣakojọpọ L1
Oṣuwọn sisan: 0.5 milimita / min
Iwọn abẹrẹ: 20µL
Ibamu eto
Apeere: Standard ojutu
Awọn ibeere ibamu
Iyatọ boṣewa ibatan: NMT 6.0% fun idapọ ti o jọmọ orlistat E tente oke
Onínọmbà
Awọn apẹẹrẹ: Ojutu boṣewa ati ojutu Ayẹwo
Ṣe iṣiro ipin ogorun aimọ yii ni apakan ti Orlistat ti o mu:
Esi = (rU/rS) × (CS/CU) × 100
rU = idahun ti o ga julọ fun orlistat ti o ni ibatan E ni ojutu Ayẹwo
rS = idahun ti o ga julọ fun USP Orlistat Compound Jẹmọ E RS ni ojutu Standard
CS = ifọkansi ti USP Orlistat Compound Jẹmọ E RS ni ojutu Standard (mg/mL)
CU = ifọkansi ti Orlistat ninu ojutu Ayẹwo (mg/mL)
Awọn ilana gbigba
Aimọ ẹni kọọkan: NMT 0.2% ti orlistat ti o ni ibatan agbo E ni a rii.
Lapapọ awọn idoti: NMT 1.0% ti awọn aimọ lapapọ ni a rii, awọn abajade fun Awọn ilana 1, 2, 3, 4, ati 5 ni afikun.
Awọn idanwo pataki
• Yiyi opitika, Yiyi pato <781>
Ojutu ayẹwo: 30 miligiramu / milimita ni oti ti o gbẹ
Awọn ibeere gbigba: Laarin -48.0 ati -51.0, ni 20
• Ipinnu Omi, Ọna Ic <921>: NMT 0.2%
Awọn ibeere afikun
• Iṣakojọpọ ati Ibi ipamọ: Fipamọ sinu awọn apoti ti o ni pipade daradara laarin 2 ati 8℃.
• Awọn Ilana Itọkasi USP <11>
USP Orlistat RS
USP Orlistat Jẹmọ Agbo A RS
USP Orlistat Jẹmọ Agbo B RS
USP Orlistat Jẹmọ Agbo C RS
USP Orlistat Jẹmọ Agbo D RS
USP Orlistat Jẹmọ Agbo E RS
USP35