Orlistat CAS 96829-58-2 API Miisaanka lumin Nadiifnimada Daawada 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 leh (3S,4S) -3-hexyl-4-[(2S) -2-hydroxytridecyl]-2-oxetanone [96829-58-2].
Qeexitaan
Orlistat waxa uu ka kooban yahay NLT 98.0% iyo NMT 101.5% ee C29H53NO5, oo lagu xisaabiyo anhydrous, bilaa dareere ah.
AQOONSIGA
• A. Nuugista Infrared <197M>
B. Wakhtiga haynta ee ugu sarraysa ee xal muunadu waxay u dhigantaa kan xalalka caadiga ah, sida lagu helay Assay.
ASSAY
Habka
[Xusuusin-Ka fogow isticmaalka caagagga caaga ah ee diyaarinta ama xakamaynta xal kasta ee falanqayntan.]
Marxaladda wareega: Acetonitrile, fosfooraska acid, iyo biyaha (860: 0.05: 140)
Xalka caadiga ah: 0.5 mg/mL ee USP Orlistat RS ee wajiga mobilada.Isku durka ka dib diyaarinta ama ku kaydi 5.
Xalka muunada: 0.5 mg/mL ee Orlistat ee wajiga mobilada.Isku durka ka dib diyaarinta ama ku kaydi 5.
Nidaamka Chromatographic
(Fiiri Chromatography <621>, Habboonaanta Nidaamka.)
Habka: LC
Baaraha: UV 195
Tiirka: 3.9-mm × 15-cm;4-µm xirmo L1
Heerka socodka: 1.0 ml/min
Cabbirka duritaanka: 20 µL
Ku habboonaanta nidaamka
Tusaale: Xalka caadiga ah
Shuruudaha ku habboonaanta
Qiyaasta heerka qaraabada: NMT 2.0%
Falanqaynta
Tusaalooyinka: Xalka caadiga ah iyo xalalka muunada
Xisaabi boqolkiiba orlistat (C29H53NO5) ee qaybta Orlistat ee la qaatay:
Natiijadu = (rU/rS) × (CS/CU) × 100
rU = jawaabta ugu sarreysa ee xalka Tusaalaha
rS = jawaabta ugu sarreysa ee xalalka caadiga ah
CS = diiradda USP Orlistat RS ee xalka caadiga ah (mg/mL)
CU = uruurinta Orlistat ee xalka Tusaalaha (mg/mL)
Shuruudaha aqbalaadda: 98.0% -101.5% ku salaysan anhydrous, dareere-free
XANUUNKA
wasakhda aan noolaha ahayn
• Hadhaaga dabka <281>: NMT 0.1%
• Biraha culus, Habka II <231>: 20 ppm
Waxyeellada dabiiciga ah
Habka 1: Xadka Orlistat La Xiriira Isku-dhafka A
Xalka caadiga ah: 0.1 mg/mL ee USP Orlistat La Xiriira Isku-dhafka A RS ee acetone
Xalka muunada: 50 mg/mL of Orlistat in acetone
Nidaamka Chromatographic
(Fiiri Chromatography <621>, Chromatography-ka-dhuuban.)
Habka: TLC
Adsorbent: 0.25-mm lakabka silica jel chromatographic ah
Codsiga mugga: 10µL
Horumarinta nidaamka dareeraha: Toluene iyo ethyl acetate (4: 1)
Xalka ogaanshaha: Ku wareeji 2.5 g oo ah phosphomolybdic acid iyo 1 g oo ah sulfate ceric sulfate 100-mL galaas mug leh, ku milmi oo ku milmi methanol ilaa mugga.
Falanqaynta
Tusaalooyinka: Xalka caadiga ah iyo xalalka muunada
Saxanka ka saar, oo si fiican u qalaji.Ku buufi saxan qallalan oo leh xal ogaanshaha, oo saxanka ku rid foornada 120 30 daqiiqo.
Shuruudaha aqbalaadda: Meel kasta oo labaad oo ka socota xalka Tusaalaha ee u dhigma orlistat-ka laxiriira xayndaabka A kama badna meesha u dhiganta ee xalinta caadiga ah (0.2%).
Habka 2: Xadka Orlistat La Xiriira Isku-dhafka B
Xalka caadiga ah: 0.025 mg/mL ee USP Orlistat Isku-xidhka B RS ee methylene chloride
Xalka muunada: 50 mg/mL of Orlistat in methylene chloride
Xalka muunada sped: 50 mg/mL ee Orlistat ee xalalka caadiga ah
Nidaamka Chromatographic
(Fiiri Chromatography <621>, Habboonaanta Nidaamka.)
Qaabka: GC
Baaraha: ionization ololka
Tiirka: 0.32-mm x 30-m silica isku dhafan, oo lagu dahaadhay weji taagan 0.25-µm G27
Heerkulka tiirka: Eeg shaxda barnaamijka heerkulka hoose.
Heerkulka Hore () Heerkulka Sare (/min) Heerkulka ugu dambeeya
50 4 170 -
170 30 300 30
Heerkulka
Durida: 270
Baadiye: 280
Gaasta qaada: Helium
Heerka socodka: 30 ml/min
Saamiga kala baxa: 10:1
Cabbirka duritaanka: 2µL
Ku habboonaanta nidaamka
Tusaale: Xalka caadiga ah
Shuruudaha ku habboonaanta
Qiyaasta heerka qaraabada: NMT 10.0%
Falanqaynta
Tusaalooyinka: Xalka muunada iyo xal muunada sped
Xisaabi boqolleyda Orlistat laxiriira xayndaabka B ee qaybta Orlistat ee la qaatay:
Natiijadu = [rU/(rSP rU)] × (CS/CT) × 100
rU = jawaabta ugu sarreysa ee orlistat-ka laxiriirta xayndaabka B ee xalka Tusaalaha
rSP = jawaabta ugu sarreysa ee orlistat laxiriirta xayndaabka B ee ka imanaya muunada muunada Spiked
CS = fiirsashada USP Orlistat Isku dhafka B RS ee xalka caadiga ah (mg/mL)
CT = fiirsashada Orlistat ee xalka muunada Spiked (mg/mL)
Shuruudaha aqbalaadda: NMT 0.05% ee iskudarka Orlistat ee B waa la helay.
Habka 3
[Xusuusin-Ka fogow isticmaalka caagagga caaga ah ee diyaarinta ama xakamaynta xal kasta ee falanqayntan.]
Marxaladda wareegta, xalalka caadiga ah, iyo xal muunad: U diyaari sida lagu faray Imtixaanka.
Xalka ku habboonaanta nidaamka: 10 µg/mL ee USP Orlistat RS, 0.1 µg/mL ee USP Orlistat La xidhiidha Isku-dhafka C RS, iyo 0.25 µg/mL ee USP Orlistat Compound D RS ee wejiga moobilka
Nidaamka Chromatographic
(Fiiri Chromatography <621>, Habboonaanta Nidaamka.)
U wad sida lagu faray Assay, marka laga reebo chromatograph-ka xalka ku habboonaanta nidaamka.
Ku habboonaanta nidaamka
Tusaalaha: Xalka ku habboonaanta nidaamka
Shuruudaha ku habboonaanta
Saamiga calaamad-ilaa-sanqad: NLT 3 ee xarunta orlistat ee laxiriirta C iyo iskudarka laxiriira D ee ugu sarreeya
Qiyaasta heerka qaraabada: NMT 10.0% ee heerka ugu sarreeya ee orlistat
Falanqaynta
Tusaalooyinka: Xalka caadiga ah iyo xalalka muunada
Xisaabi boqolkiiba wasakh kasta ee qaybta Orlistat ee la qaatay:
Natiijadu = (rU/rS) × (CS/CU) × (1/F) × 100
rU = jawaabta ugu sarraysa ee qof kasta oo nijaas ah oo ka yimid xalka Tusaalaha
rS = jawaabta ugu sarreysa ee USP Orlistat RS oo ka timid xalalka caadiga ah
CS = diiradda USP Orlistat RS ee xalka caadiga ah (mg/mL)
CU = uruurinta Orlistat ee xalka Tusaalaha (mg/mL)
F = jawaab celin qaraabo ah sida lagu sheegay Shaxda 1
Shuruudaha aqbalaadda: eeg Shaxda 1aad ee wasakhnimada.
Shaxda wasakhaysan 1
Magaca Wakhtiga Haynta Qaraabada Shuruudaha Ogolaanshaha Qodobbada Jawaabta Qaraabo, NMT (%)
Formylleucinea 0.10 4.0 0.2
Xarunta laxiriirta Orlistat C 0.13 33 0.05
Orlistat giraanta furan ee epimerb 0.44 1.0 0.2
Xarunta Orlistat laxiriirta D* 0.90 - Lagu xisaabiyay gudaha
Habka 4
Orlistat giraanta furan amidec* 0.90 - Waxaa lagu xisaabiyay gudaha
Habka 4
Orlistat 1.00 - -
d-Leucine orlistatd 1.18 1.0 0.2
Nijaasnimada shakhsi ahaaneed ee aan la aqoonsan - 1.0 0.1
* Coelutes ee nidaamkan LC, lagu go'aamiyay iyadoo la isticmaalayo Habka 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 ama enantiomer.
Habka 4: Xadka Isku-dhafka Orlistat ee D
Marxaladda guurguura: Methanol iyo biyaha (83:17)
Xalka ku habboonaanta nidaamka: 4 mg/mL ee USP Orlistat RS iyo 2.4 µg/mL ee USP Orlistat Compound D RS ee acetonitrile, siday u kala horreeyaan
Xalka caadiga ah: 5.0 mg/mL ee USP Orlistat RS ee acetonitrile
Xalka muunada: 5.0 mg/mL of Orlistat in acetonitrile
Nidaamka Chromatographic
(Fiiri Chromatography 621, Habboonaanta Nidaamka.)
Habka: LC
Baaraha: 205 nm
Tiirka: 4.0-mm × 25-cm;5-µm xirmo L7
Heerka socodka: 0.6 ml/min
Cabbirka duritaanka: 20 µL
Ku habboonaanta nidaamka
Tusaalaha: Xalka ku habboonaanta nidaamka
Shuruudaha ku habboonaanta
Saamiga calaamad-ilaa-sanqa: NLT 3 ee isku xidhka orlistat ee laxidhiidha D ugu sarreysa
Qiyaasta heerka qaraabada: NMT 10.0% ee heerka ugu sarreeya ee orlistat
Falanqaynta
Tusaalooyinka: Xalka caadiga ah iyo xalalka muunada
Xisaabi boqolkiiba wasakh kasta ee qaybta Orlistat ee la qaatay:
Natiijadu = (rU/rS) × (CS/CU) × (1/F) × 100
rU = jawaabta ugu sarraysa ee qof kasta oo nijaas ah oo ka yimid xalka Tusaalaha
rS = jawaabta ugu sarreysa ee USP Orlistat RS ee xalka caadiga ah
CS = fiirsashada USP Orlistat RS ee xalka caadiga ah (µg/mL)
CU = fiirsashada Orlistat ee xalka Tusaalaha (µg/mL)
F = jawaab celin qaraabo ah sida lagu helay Jaantuska wasakhnimada 2
Shuruudaha aqbalaadda: Fiiri Shaxda 2aad ee wasakhnimada.
Shaxda wasakhaysan 2
Magaca Wakhtiga Haynta Qaraabada Shuruudaha Ogolaanshaha Qodobbada Jawaabta Qaraabo, NMT (%)
Xarunta Orlistat ee la xidhiidha D 0.94 1.0 0.2
Orlistat 1.00 - -
Orlistat giraanta furan 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.
Habka 5: Xadka Isku-dhafka Orlistat La Xiriira E
Buffer: 0.4 N xalinta borate, lagu hagaajiyay pH ee 10.2
Wakiilka soo saarida: o-Phthaldehyde (OPA) xal.[Xusuusin-Haddii aan la heli karin ganacsi ahaan, wakiilka Derivitizing waxaa loo diyaarin karaa 1% mid kasta oo ah 3-mercaptopropionic acid iyo o-phthaldialdehyde ee 0.4M borate borate solution.]
Xalka A: Ku wareeji 4.1 g oo ah sodium acetate trihydrate iyo 40 mg ee ethylenediaminetetraacetic acid (EDTA) oo ku shub weel 1-L ah.Ku milmi 950 mL oo biyo ah, kuna hagaaji 0.1 N sodium hydroxide una beddel pH ah 7.2.Ku qas biyo ilaa mugga, ku dar 2.5 mL oo tetrahydrofuran ah, oo qas.Shaandhee, iyo degas.
Xalka B: Ku wareeji 2.7 g oo ah sodium acetate trihydrate iyo 40 mg ee EDTA galka mugga 1-L.Ku milmi 200 ml oo biyo ah, kuna hagaaji 0.1 N sodium hydroxide una beddel pH 7.2 ah.Ku dar 800 mL oo ah acetonitrile, filter, iyo degas.
Marxaladda guurguura: Eeg shaxda gradient ee hoose.
Waqtiga (min) Xalka A (%) Xalka 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
Xalka caadiga ah: Ku wareeji tiro miisaan ah oo ku saabsan 0.2 mg ee USP Orlistat Laxiriirta iskudarka E RS 20-mL dhalo-madaxeed.Ku dar 10 ml oo ah 4 N sodium hydroxide, oo xidh fiilada.Kuleyli fiishka ilaa 100 ilaa 1 saac, ka dibna u ogolow inaad ku qaboojiso heerkulka qolka.Ku wareeji 2 mL ee xalka ka soo baxay galaas mug leh oo 50-mL ah, oo ku qas biyo ilaa mugga.Ilaa 0.5 mL ee xalkan ku dar 2.0 ml oo Buffer ah iyo 0.5 mL oo ah wakiilka soo saarida.
Xalka Tusaalaha: Ku sii soco sida lagu faray xalinta caadiga ah, laakiin taa beddelkeeda isticmaal 25 mg Orlistat si aad u bedesho 0.2 mg ee USP Orlistat La Xiriira Isku-dhafka E RS.
Nidaamka Chromatographic
(Fiiri Chromatography <621>, Habboonaanta Nidaamka.)
Habka: LC
Dareemiyaha: Fluorescence 340 nm (xariir);450 nm
Tiirarka
Ilaalada: 2.1-mm × 2-cm;50-µm xirmo L1
Falanqaynta: 2.1-mm × 20-cm;xirxiran L1
Heerka socodka: 0.5 ml/min
Cabbirka duritaanka: 20 µL
Ku habboonaanta nidaamka
Tusaale: Xalka caadiga ah
Shuruudaha ku habboonaanta
Isbeddelka heerka qaraabada ah: NMT 6.0% ee qaybta E ugu sarreysa ee Orlistat
Falanqaynta
Tusaalooyinka: Xalka caadiga ah iyo xalalka muunada
Xisaabi boqolkiiba wasakhnimadan qaybta Orlistat ee la qaatay:
Natiijadu = (rU/rS) × (CS/CU) × 100
rU = jawaabta ugu sarreysa ee orlistat laxiriirta E ee xalka Tusaalaha
rS = jawaabta ugu sarreysa ee USP Orlistat Isku-xidhka E RS ee xalka caadiga ah
CS = fiirsashada USP Orlistat Isku dhafka E RS ee xalka caadiga ah (mg/mL)
CU = uruurinta Orlistat ee xalka Tusaalaha (mg/mL)
Shuruudaha aqbalaadda
Nijaasnimada shaqsiga ah: NMT 0.2% ee walaxda la xidhiidha Orlistat E waa la helay.
Wadarta wasakhda: NMT 1.0% wadarta wasakhda ayaa la helay, natiijooyinka habraacyada 1, 2, 3, 4, iyo 5 waa lagu daray.
IMTIXAANO GAAR AH
• Wareegga indhaha, Wareegga Gaarka ah <781>
Xalka muunada: 30 mg/mL ee khamriga fuuqbaxay
Shuruudaha aqbalaadda: Inta u dhaxaysa -48.0 iyo -51.0, at 20
• Go'aaminta Biyaha, Habka Ic <921>: NMT 0.2%
SHURUUD DHEERAAD AH
Baakadaha iyo Kaydinta: Ku kaydi weelasha si fiican u xidhan inta u dhaxaysa 2 iyo 8℃.
• Heerarka Tixraaca USP <11>
USP Orlistat RS
Isku dhafka USP Orlistat La Xiriira A RS
Isku dhafka USP Orlistat La Xiriira B RS
Isku dhafka USP Orlistat La Xiriira C RS
Isku dhafka USP Orlistat La Xiriira D RS
Isku dhafka USP Orlistat La Xiriira E RS
USP35