Orlistat CAS 96829-58-2 API Kuchepetsa Kulemera kwa Mankhwala Kuyeretsa 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 yokhala ndi (3S,4S) -3-hexyl-4-[(2S) -2-hydroxytridecyl] -2-oxetanone [96829-58-2].
TANTHAUZO
Orlistat ili ndi NLT 98.0% ndi NMT 101.5% ya C29H53NO5, yowerengedwa pa maziko a anhydrous, opanda zosungunulira.
CHIZINDIKIRO
• A. Infrared Absorption <197M>
• B. Nthawi yosungira pachimake chachikulu cha Sample solution ikufanana ndi ya Standard solution, monga momwe zapezedwa mu Assay.
ZOYESA
• Ndondomeko
[Zindikirani-Pewani kugwiritsa ntchito mabotolo apulasitiki pokonzekera kapena kusunga yankho lililonse pakuwunikaku.]
Gawo lam'manja: Acetonitrile, phosphoric acid, ndi madzi (860: 0.05: 140)
Yankho lokhazikika: 0.5 mg/mL ya USP Orlistat RS mu gawo la Mobile.Jekeseni mukangokonzekera kapena sungani pa 5.
Yankho lachitsanzo: 0.5 mg/mL ya Orlistat mu gawo la Mobile.Jekeseni mukangokonzekera kapena sungani pa 5.
Chromatographic system
(Onani Chromatography <621>, Kukwanira Kwadongosolo.)
Njira: LC
Chowunikira: UV 195
Mzere: 3.9-mm × 15-cm;4-µm kunyamula L1
Kuthamanga: 1.0 mL / min
Kukula kwa jekeseni: 20µL
Kuyenerera kwadongosolo
Chitsanzo: Njira yothetsera
Zofunikira zoyenera
Kupatuka kofananira: NMT 2.0%
Kusanthula
Zitsanzo: Yankho lokhazikika ndi yankho lachitsanzo
Werengani kuchuluka kwa orlistat (C29H53NO5) mu gawo la Orlistat lomwe latengedwa:
Zotsatira = (rU/rS) × (CS/CU) × 100
rU = kuyankha kwapamwamba kuchokera ku Sample solution
rS = kuyankha kwakukulu kuchokera ku Standard solution
CS = kuchuluka kwa USP Orlistat RS mu Standard solution (mg/mL)
CU = kuchuluka kwa Orlistat mu Sample solution (mg/mL)
Njira zolandirira: 98.0% -101.5% pamtundu wa anhydrous, wopanda zosungunulira
ZOCHITSA
Zowonongeka Zachilengedwe
• Zotsalira pakuyatsa <281>: NMT 0.1%
• Zitsulo Zolemera, Njira II <231>: 20 ppm
Zowonongeka Zachilengedwe
• Ndondomeko 1: Malire a Orlistat Related Compound A
Yankho lokhazikika: 0.1 mg/mL ya USP Orlistat Related Compound A RS mu acetone
Yankho lachitsanzo: 50 mg/mL ya Orlistat mu acetone
Chromatographic system
(Onani Chromatography <621>, Thin-Layer Chromatography.)
Njira: TLC
Adsorbent: 0.25-mm wosanjikiza wa chromatographic silica gel osakaniza
Kuchuluka kwa ntchito: 10 µL
Kupanga zosungunulira: Toluene ndi ethyl acetate (4:1)
Njira yodziwira: Chotsani 2.5 g wa phosphomolybdic acid ndi 1 g wa cerric sulfate mu botolo la volumetric 100-mL, sungunulani ndi kusungunula ndi methanol mpaka voliyumu.
Kusanthula
Zitsanzo: Yankho lokhazikika ndi yankho lachitsanzo
Chotsani mbaleyo, ndikuyimitsa bwino.Thirani mbale zouma ndi njira ya Detection, ndikuyika mbale mu uvuni pa madigiri 120 kwa 30 min.
Njira zolandirira: Malo aliwonse achiwiri kuchokera ku Sample solution yofanana ndi orlistat yokhudzana ndi gulu A siili yolimba kuposa malo ofananirako kuchokera ku Standard solution (0.2%).
• Ndondomeko 2: Malire a Orlistat Related Compound B
Njira yothetsera: 0.025 mg/mL ya USP Orlistat Related Compound B RS mu methylene chloride
Yankho lachitsanzo: 50 mg/mL ya Orlistat mu methylene chloride
Yankho lachitsanzo la Spiked: 50 mg/mL ya Orlistat mu Standard solution
Chromatographic system
(Onani Chromatography <621>, Kukwanira Kwadongosolo.)
Njira: GC
Chodziwira: Moto ionization
Mzere: 0.32-mm x 30-m silika wosakanikirana, wokutidwa ndi gawo loyima la 0.25-µm G27
Kutentha kwa mgawo: Onani tebulo la pulogalamu ya kutentha pansipa.
Kutentha Koyambirira () Kutentha Kwakanthawi (/min) Kutentha Komaliza () Kugwira Nthawi Pamatenthedwe Omaliza (mphindi)
50 4 170 -
170 30 300 30
Kutentha
jekeseni: 270
Chowunikira: 280
Gasi wonyamula: Helium
Kuthamanga: 30 mL / min
Chiŵerengero cha kugawanika: 10: 1
Kukula kwa jakisoni: 2 µL
Kuyenerera kwadongosolo
Chitsanzo: Njira yothetsera
Zofunikira zoyenera
Kupatuka kofananira: NMT 10.0%
Kusanthula
Zitsanzo: Yankho lachitsanzo ndi yankho la Spiked
Werengani kuchuluka kwa orlistat yokhudzana ndi gulu B mu gawo la Orlistat lomwe latengedwa:
Zotsatira = [rU/(rSP rU)] × (CS/CT) × 100
rU = kuyankha kwapamwamba kwa orlistat yokhudzana ndi gulu B kuchokera ku Sample solution
rSP = kuyankha kwapamwamba kwa orlistat yokhudzana ndi gulu B kuchokera ku Spiked solution solution
CS = kuchuluka kwa USP Orlistat Related Compound B RS mu Standard solution (mg/mL)
CT = kuchuluka kwa Orlistat mu njira ya Spiked (mg/mL)
Njira zovomerezeka: NMT 0.05% ya orlistat yokhudzana ndi gulu B imapezeka.
• Ndondomeko 3
[Zindikirani-Pewani kugwiritsa ntchito mabotolo apulasitiki pokonzekera kapena kusunga yankho lililonse pakuwunikaku.]
Mobile phase, Standard solution, ndi Sample solution: Konzekerani monga mwauzira mu Assay.
Yankho loyenerera pamakina: 10 µg/mL ya USP Orlistat RS, 0.1 µg/mL ya USP Orlistat Related Compound C RS, ndi 0.25 µg/mL ya USP Orlistat Related Compound D RS mugawo la Mobile
Chromatographic system
(Onani Chromatography <621>, Kukwanira Kwadongosolo.)
Pitirizani monga momwe mwanenera mu Assay, kupatula pa chromatograph yankho lokwanira la System.
Kuyenerera kwadongosolo
Zitsanzo: Yankho lolingana ndi dongosolo
Zofunikira zoyenera
Chiŵerengero cha Signal-to-Noise: NLT 3 ya orlistat yokhudzana ndi C ndi orlistat yokhudzana ndi nsonga za D
Kupatuka kofananira: NMT 10.0% pachimake cha orlistat
Kusanthula
Zitsanzo: Yankho lokhazikika ndi yankho lachitsanzo
Werengani kuchuluka kwa zodetsa zilizonse mu gawo la Orlistat lomwe latengedwa:
Zotsatira = (rU/rS) × (CS/CU) × (1/F) × 100
rU = kuyankha kwapamwamba pazodetsa zamunthu aliyense kuchokera ku Sample solution
rS = kuyankha kwakukulu kwa USP Orlistat RS kuchokera ku Standard solution
CS = kuchuluka kwa USP Orlistat RS mu Standard solution (mg/mL)
CU = kuchuluka kwa Orlistat mu Sample solution (mg/mL)
F = yankho lachibale monga laperekedwa mu Gulu 1 la Zosayera
Njira zovomerezera: Onani Table 1 ya Zonyansa.
Table 1
Tchulani Chiyankhulo Chosunga Nthawi Yogwirizana ndi Mayankho Zomwe Mumavomereza, NMT (%)
Formylleucinea 0.10 4.0 0.2
Orlistat yokhudzana ndi gulu C 0.13 33 0.05
Orlistat yotsegula mphete epimerb 0.44 1.0 0.2
Orlistat yokhudzana ndi gulu D * 0.90 - Yowerengedwa mkati
Ndondomeko 4
Orlistat tsegulani mphete amidec * 0.90 - Yowerengedwa mkati
Ndondomeko 4
Orlistat 1.00 - -
d-Leucine orlistatd 1.18 1.0 0.2
Chidetso chamunthu payekhapayekha - 1.0 0.1
* Ma Coelutes mu dongosolo la LC ili, otsimikiza kugwiritsa ntchito Procedure 4.
ndi 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 kapena enantiomer.
• Ndondomeko 4: Malire a Orlistat Related Compound D
Gawo lam'manja: Methanol ndi madzi (83:17)
Njira yothetsera vutoli: 4 mg/mL ya USP Orlistat RS ndi 2.4 µg/mL ya USP Orlistat Related Compound D RS mu acetonitrile, motsatira
Njira yothetsera: 5.0 mg/mL ya USP Orlistat RS mu acetonitrile
Yankho lachitsanzo: 5.0 mg/mL ya Orlistat mu acetonitrile
Chromatographic system
(Onani Chromatography 621, System Suitability.)
Njira: LC
Chowunikira: 205 nm
Mzere: 4.0-mm × 25-cm;5-µm kunyamula L7
Kuthamanga: 0.6 mL / min
Kukula kwa jekeseni: 20µL
Kuyenerera kwadongosolo
Zitsanzo: Yankho lolingana ndi dongosolo
Zofunikira zoyenera
Chiŵerengero cha Signal-to-Noise: NLT 3 ya orlistat yokhudzana ndi chigawo cha D
Kupatuka kofananira: NMT 10.0% pachimake cha orlistat
Kusanthula
Zitsanzo: Yankho lokhazikika ndi yankho lachitsanzo
Werengani kuchuluka kwa zodetsa zilizonse mu gawo la Orlistat lomwe latengedwa:
Zotsatira = (rU/rS) × (CS/CU) × (1/F) × 100
rU = kuyankha kwapamwamba pazodetsa zamunthu aliyense kuchokera ku Sample solution
rS = kuyankha kwapamwamba kwa USP Orlistat RS kuchokera ku Standard solution
CS = kuchuluka kwa USP Orlistat RS mu Standard solution (µg/mL)
CU = kuchuluka kwa Orlistat mu Sample solution (µg/mL)
F = chinthu choyankhidwa chachibale monga momwe chapezedwera mu Kusayera Table 2
Njira zovomerezera: Onani Table 2 ya Zonyansa.
Table 2
Tchulani Chiyankhulo Chosunga Nthawi Yogwirizana ndi Mayankho Zomwe Mumavomereza, NMT (%)
Orlistat yokhudzana ndi gulu D 0.94 1.0 0.2
Orlistat 1.00 - -
Orlistat tsegulani mphete 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.
• Ndondomeko 5: Malire a Orlistat Related Compound E
Buffer: 0.4 N borate solution, yosinthidwa kukhala pH ya 10.2
Deriviting agent: yankho la o-Phthaldehyde (OPA).[Zindikirani-Ngati simungathe kupeza malonda, Derivitizing agent ikhoza kukonzedwa ngati 1% iliyonse ya 3-mercaptopropionic acid ndi o-phthaldialdehyde mu 0.4 M borate buffer solution.]
Yankho A: Tumizani 4.1 g ya sodium acetate trihydrate ndi 40 mg ya ethylenediaminetetraacetic acid (EDTA) mu botolo la 1-L la volumetric.Sungunulani mu 950 mL yamadzi, ndikusintha ndi 0.1 N sodium hydroxide ku pH ya 7.2.Sungunulani ndi madzi mpaka voliyumu, onjezerani 2.5 mL wa tetrahydrofuran, ndikusakaniza.Zosefera, ndi degas.
Yankho B: Tumizani 2.7 g ya sodium acetate trihydrate ndi 40 mg ya EDTA mu botolo la 1-L la volumetric.Sungunulani mu 200 ml ya madzi, ndipo sinthani ndi 0.1 N sodium hydroxide ku pH ya 7.2.Onjezani 800 ml ya acetonitrile, fyuluta, ndi degas.
Gawo la m'manja: Onani tebulo la gradient pansipa.
Nthawi (mphindi) Yankho A (%) Yankho B (%)
0 96.7 3.3
20 6040
24 0100
38 0100
38 96.7 3.3
45 96.7 3.3
Yankho lokhazikika: Tumizani kuchuluka koyezera pafupifupi 0.2 mg wa USP Orlistat Related compound E RS mu 20-mL mutu-space vial.Onjezani 10 ml ya 4 N sodium hydroxide, ndikutseka vial.Kutenthetsa vial mpaka 100 kwa 1 h, kenaka mulole kuziziritsa kutentha.Tumizani 2 ml ya yankho mu botolo la voliyumu ya 50-mL, ndikusungunula ndi madzi mpaka voliyumu.Pa 0.5 ml ya yankho ili onjezerani 2.0 mL ya Buffer ndi 0.5 ml ya Derivatizing agent.
Yankho lachitsanzo: Pitirizani monga momwe mukufunira ku Standard solution, koma m'malo mwake mugwiritseni ntchito 25 mg ya Orlistat kuti musinthe 0.2 mg ya USP Orlistat Related Compound E RS.
Chromatographic system
(Onani Chromatography <621>, Kukwanira Kwadongosolo.)
Njira: LC
Chowunikira: Fluorescence 340 nm (chisangalalo);450nm (kutulutsa)
Mizati
Mlonda: 2.1-mm × 2-cm;50-µm kunyamula L1
Kusanthula: 2.1-mm × 20-cm;kunyamula L1
Kuthamanga: 0.5 mL / min
Kukula kwa jekeseni: 20µL
Kuyenerera kwadongosolo
Chitsanzo: Njira yothetsera
Zofunikira zoyenera
Kupatuka kofananira: NMT 6.0% ya orlistat yogwirizana ndi E pachimake
Kusanthula
Zitsanzo: Yankho lokhazikika ndi yankho lachitsanzo
Werengetsani kuchuluka kwa zodetsa izi mu gawo la Orlistat lomwe latengedwa:
Zotsatira = (rU/rS) × (CS/CU) × 100
rU = kuyankha kwapamwamba kwa orlistat yokhudzana ndi chigawo E mu Sample solution
rS = kuyankha kwapamwamba kwa USP Orlistat Related Compound E RS mu Standard solution
CS = kuchuluka kwa USP Orlistat Related Compound E RS mu Standard solution (mg/mL)
CU = kuchuluka kwa Orlistat mu Sample solution (mg/mL)
Zovomerezeka zovomerezeka
Kudetsedwa kwa munthu payekha: NMT 0.2% ya orlistat yokhudzana ndi mankhwala E amapezeka.
Zonyansa zonse: NMT 1.0% ya zonyansa zonse zapezeka, zotsatira za Njira 1, 2, 3, 4, ndi 5 zikuwonjezedwa.
MAYESO AKE
• Kuzungulira kwa Optical, Kuzungulira Kwachindunji <781>
Yankho lachitsanzo: 30 mg/mL mu mowa wopanda madzi
Njira zolandirira: Pakati pa -48.0 ndi -51.0, pa 20
• Kutsimikiza kwa Madzi, Njira Ic <921>: NMT 0.2%
ZOWONJEZERA ZOFUNIKA
• Kupaka ndi Kusunga: Sungani m’zotengera zotsekedwa bwino pakati pa 2 ndi 8℃.
• USP Reference Standards <11>
USP Orlistat RS
USP Orlistat Related Compound A RS
USP Orlistat Yogwirizana Compound B RS
USP Orlistat Yogwirizana Compound C RS
USP Orlistat Yogwirizana Compound D RS
USP Orlistat Related Compound E RS
USP35