Paclitaxel (Taxol) CAS 33069-62-4 Assay (HPLC) 97.0 ~ 102.0%

Paclitaxel
C47H51NO14 853.91
Benzenepropanoic acid, (benzoylamino) --hydroxy-, 6,12b-bis (acetyloxy) -12- (benzoyloxy) -2a,3,4,4a,5,6,9,10,11,12,12a,12b -dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4] benz [1,2-b] oxet-9-yl ester, [2aR-[2a,4,4a,6,9(R*,S*),11,12,12a,12b]]-.
(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS) -1,2a,3,4,4a,6,9,10,11,12,12a,12b-Dodecahydro-4,6, 9,11,12,12b-hexahydroxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4] -benz [1,2-b] oxet-5-daya 6, 12b-diacetate, 12-benzoate, 9-ester tare da (2R,3S) -N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel ya ƙunshi ba kasa da kashi 97.0 ba kuma bai wuce kashi 102.0 na C47H51NO14 ba, wanda aka ƙididdige shi akan tushen anhydrous, mara ƙarfi.
[Cution-Paclitaxel shine cytotoxic.Ya kamata a kula sosai don hana shakar Paclitaxel da bayyanar da fata gare ta.]
Marufi da ajiya-Ajiye a cikin matsattsu, kwantena masu jure haske, da adanawa a yanayin zafin ɗaki mai sarrafawa.
Lakabi-Lakabin yana nuna nau'in tsari da aka yi amfani da shi don samar da kayan da gwajin mahadi masu alaƙa waɗanda kayan ya cika da su.
Matsayin Magana na USP <11>-
USP Endotoxin RS
USP Paclitaxel RS Danna don Duba Tsarin
Abubuwan da ke da alaƙa da USP Paclitaxel A RS
Cephalomannine.
Abubuwan da ke da alaƙa da USP Paclitaxel B RS
10-Deacetyl-7-Epipaclitaxel.
USP Paclitaxel Haɗin Tsabtace RS
Cakuda na Paclitaxel da mahadi masu zuwa: propyl analog, cephalomannine, sec-butyl analog, n-butyl analog, benzyl analog, baccatin VI, pentyl analog, da 7-epipaclitaxel.
Ganewa-
A: Ciwon Infrared <197K>.
B: Lokacin riƙewa na babban kololuwa a cikin chromatogram na shirye-shiryen Assay ya dace da abin da ke cikin chromatogram na daidaitaccen shiri, kamar yadda aka samu a cikin Assay.
Takamaiman jujjuyawar 781S: tsakanin 49.0 da 55.0 a 20, an ƙididdige su akan tushen rashin ƙarfi, rashin ƙarfi.
Maganin gwaji: 10 MG kowace ml, a cikin methanol.
Gwaje-gwajen ƙididdiga na ƙananan ƙwayoyin cuta <61> da Gwaje-gwaje don ƙayyadaddun ƙwayoyin cuta <62>-Jimlar ƙidayar ƙwayoyin cuta na aerobic baya wuce 100 cfu a kowace g.Ya cika ka'idodin gwaje-gwaje don rashin Staphylococcus aureus, Pseudomonas aeruginosa, nau'in Salmonella, da Escherichia coli.
Bacterial endotoxins 85-Ba ya ƙunshi fiye da 0.4 USP Endotoxin Unit da MG na paclitaxel.
Ruwa, Hanyar Ic <921>: bai wuce 4.0% ba.
Ragowa akan kunnawa <281>: bai wuce 0.2% ba.
Karfe masu nauyi, Hanyar II <231>: 0.002%.
Abubuwan da ke da alaƙa-
gwajin 1 (don kayan da aka yi wa lakabi da keɓe daga tushen halitta) - Idan kayan ya bi wannan gwajin, lakabin yana nuna cewa ya haɗu da abubuwan haɗin gwiwar USP Gwajin 1.
Diluent-Shirya kamar yadda aka umarce shi a cikin Assay.
Magani A-Shirya tacetonitrile da aka lalatar da shi.
Magani B-Shirya tacewa da kuma gurɓataccen ruwa.
Lokacin wayar hannu-Yi amfani da gauraya masu canji na Magani A da Magani B kamar yadda aka umurce su don tsarin Chromatographic.Yi gyare-gyare idan ya cancanta (duba Dacewar Tsarin ƙarƙashin Chromatography 621).
Maganin dacewa da tsarin-Narke daidai gwargwadon awo na USP Paclitaxel Related Compound A RS da USP Paclitaxel Related Compound B RS a cikin methanol don samun maganin sananniya na kusan 10 μg na kowane ml.Canja wurin 5.0 ml na wannan maganin zuwa 50-mL flask volumetric, tsarma tare da Diluent zuwa ƙara, da haɗuwa.
Standard bayani-Narke, tare da taimakon sonication, an daidai auna yawa na USP Paclitaxel RS a diluent, da kuma tsarma quantitatively, kuma stepwise idan ya cancanta, tare da diluent don samun wani bayani ciwon san maida hankali game da 5 µg da ml.
Maganin gwaji-Yi amfani da shirye-shiryen Assay.
Tsarin Chromatographic (duba Chromatography <621>) -Chromatograph na ruwa yana sanye da na'urar ganowa 227-nm da ginshiƙin 4.6-mm × 25-cm wanda ya ƙunshi 5-µm tattara L43.Matsakaicin kwarara shine kusan 2.6 ml a minti daya.Ana kiyaye zafin jiki na ginshiƙi a 30. An tsara chromatograph kamar haka.
Lokaci (minti) Magani A (%) Magani B (%) Elution
0-35 35 65 masu son kai
35–60 35®80 65®20 layin layi
60–70 80®35 20®65 layin layi
70-80 35 65 isocraticChromatograph da tsarin dacewa da tsarin, da yin rikodin martanin kololuwa kamar yadda aka tsara don Tsari: lokutan riƙewa na dangi kusan 0.78 don abubuwan da ke da alaƙa da paclitaxel A da 0.86 don fili mai alaƙa da paclitaxel B (dangane da lokacin riƙewa don paclitaxel da aka samu daga Maganin Gwaji);da ƙuduri, R, tsakanin abubuwan da ke da alaƙa da paclitaxel A da abubuwan da ke da alaƙa da paclitaxel B bai ƙasa da 1.0 ba.Chromatograph the Standard bayani, da rikodin mafi girman martani kamar yadda aka ba da umarni don Tsari: madaidaicin ma'auni don maimaita alluran bai wuce 2.0% ba.
Tsari-Alurar ƙarar (kimanin 15 µL) na maganin gwajin a cikin chromatograph, yi rikodin chromatogram, da auna wuraren don manyan kololuwa.Yi ƙididdige adadin kowane ƙazanta a cikin ɓangaren Paclitaxel da aka ɗauka ta dabara:
100 (Juma'a / rU)
a cikin abin da F shine ma'anar mayar da martani ga kowane kololuwar ƙazanta (duba Table 1 don ƙima);ri shine yanki kololuwa ga kowane rashin tsarki;kuma rU shine yanki kololuwa na paclitaxel.
Tebur 1
Dangantakar Tsayawa Lokacin Dangantakar Amsa Factor (F) Iyakar Suna (%)
0.24 1.29 Baccatin III 0.2
0.53 1.00 10-Deacetylpaclitaxel 0.5
0.57 1.00 7-Xylosylpaclitaxel 0.2
0.78 1.26 Cephalomannine (abin da ke da alaƙa da Paclitaxel A) a11
0.78 1.26 2'',3''-Dihydrocephalomannin a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (abin da ke da alaƙa da Paclitaxel B) 0.5
1.10 1.00 Benzyl analog3 b12
1.10 1.00 3'',4''-Dehydropaclitaxel C b22
1.40 1.00 7-Epicephalomannin 0.3
1.85 1.00 7-Epipaclitaxel 0.5
1 Ƙidumar ƙila ba ta cika ga waɗannan kololuwa ba, ya danganta da adadin dangi;jimlar a1 da a2 bai wuce 0.5% ba.
2 Ƙidumar ƙila ba ta cika ga waɗannan kololuwa ba, ya danganta da adadin dangi;jimlar b1 da b2 bai wuce 0.5% ba.
3 Ana sanya sunan sinadarai mai zuwa ga mahaɗin da ke da alaƙa, analogin benzyl: Baccatin III 13-ester tare da (2R,3S) -2-hydroxy-3-phenyl-3- (2-phenylacetylamino) propanoic acid.
Bugu da ƙari, rashin ƙetare iyaka don ƙazantattun abubuwan da suka shafi paclitaxel a cikin Table 1, ba a sami fiye da 0.1% na kowane ƙazanta ɗaya ba;kuma ba fiye da 2.0% na jimlar ƙazanta ana samun su ba.
gwajin 2 (don kayan da aka lakafta kamar yadda aka samar ta hanyar tsarin semisynthetic) - Idan kayan ya bi wannan gwajin, lakabin yana nuna cewa ya haɗu da abubuwan haɗin gwiwar USP Gwajin 2.
Diluent-Yi amfani da acetonitrile.
Magani A-Yi amfani da cakudaccen ruwa da aka tace da kuma acetonitrile (3:2).
Magani B-Yi amfani da tacewa da kuma lalata acetonitrile.
Lokacin wayar hannu-Yi amfani da gauraya masu canji na Magani A da Magani B kamar yadda aka umurce su don tsarin Chromatographic.Yi gyare-gyare idan ya cancanta (duba Dacewar Tsarin ƙarƙashin Chromatography 621).
Maganin dacewa da tsarin-Narke daidai adadin USP Paclitaxel RS da USP Paclitaxel Related Compound B RS a cikin Diluent, girgiza da sonicating idan ya cancanta, don samun maganin da aka sani game da 0.96 MG da 0.008 MG kowace ml, bi da bi.
Magani na gwaji-Canja wurin kusan 10 MG na Paclitaxel, daidai aunawa, zuwa flask volumetric na 10-mL, narkar da kuma tsarma tare da Diluent zuwa girma, girgiza da sonicating idan ya cancanta, da haɗuwa.
Tsarin Chromatographic (duba Chromatography 621) - Na'urar chromatograph na ruwa an sanye shi da na'urar ganowa 227-nm da ginshiƙin 4.6-mm × 15-cm wanda ya ƙunshi 3-µm tattara L1.Matsakaicin kwarara shine kusan 1.2 ml a minti daya.Ana kiyaye zafin jiki na ginshiƙi a 35. An tsara chromatograph kamar haka.
Lokaci (minti) Magani A (%) Magani B (%) Elution
0-20 100 0 masu zaman kansu
20-60 100®10 0®90 layin layi
60-62 10®100 90®0 layin layi
62-70 100 0 isocraticChromatograph da tsarin dacewa da tsarin, da kuma rikodin mafi girman martani kamar yadda aka tsara don Tsari: lokutan riƙewa na dangi kusan 0.94 don fili mai alaƙa da paclitaxel B da 1.0 don paclitaxel;ƙuduri, R, tsakanin abubuwan da ke da alaƙa da paclitaxel B da paclitaxel bai kasance ƙasa da 1.2 ba;kuma madaidaicin ma'auni na dangi don kwafin injections bai wuce 2.0%.
Tsari-Na dabam allura daidai juzu'i (kimanin 15 µL) na Diluent da Maganin Gwaji a cikin chromatograph, yi rikodin chromatograms, da auna wuraren ga duk kololuwa.Yi watsi da kowane kololuwa saboda Diluent.Yi ƙididdige adadin kowane ƙazanta a cikin ɓangaren Paclitaxel da aka ɗauka ta dabara:
100 (Juma'a / s)
a cikin abin da F shine ma'anar amsawa ga kowane ƙazanta (duba Table 2 don dabi'u);ri shine yanki kololuwa ga kowane kazanta da aka samu daga maganin gwajin;kuma rs shine jimlar wuraren duk kololuwar da aka samu daga maganin gwajin.
Table 2
Dangantakar Tsayawa Lokacin Dangantakar Amsa Factor (F) Iyakar Suna (%)
0.11 1.24 10-Deacetylbaccatin III 0.1
0.20 1.29 Baccatin III 0.2
0.42 1.39 Photodegradant2 0.1
0.47 1.00 10-Deacetylpaclitaxel 0.5
0.80 1.00 2-Debenzoylpaclitaxel-2-pentenoate 0.7
0.921 1.00 Oxetane da aka buɗe, acetyl da benzoyl sun yi ƙaura2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (abin da ke da alaƙa da Paclitaxel B) x3
1.37 1.00 7-Epipaclitaxel 0.4
1.45 1.00 10,13-Bissidechainpaclitaxel2 0.5
1.54 1.00 7-Acetylpaclitaxel 0.6
1.80 1.75 13-Tes-baccatin III 0.1
2.14 1.00 7-Tes-paclitaxel 0.3
1 Ƙidumar ƙila ba ta cika ga waɗannan kololuwa ba, ya danganta da adadin dangi;jimlar x1, x2, da x3 bai wuce 0.4% ba.
2 Ana sanya sunayen sunadarai masu zuwa ga mahaɗan da ke da alaƙa Photodegradant;Oxetane zobe ya buɗe, acetyl da benzoyl sun yi hijira;da 10,13-Bissidechainpaclitaxel:
Mai daukar hoto
(1R,2R,4S,5S,7R,10S,11R,12S,13S,15S,16S)-2,10-diacetyloxy-5,13-dihydroxy-4,16,17,17-tetramethyl-8-oxa- 3-oxo-12-phenylcarbonyloxypentacyclo [11.3.1.01,11.04,11.07,10] heptadec-15-yl
(2R, 3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino) propanoate
Oxetane zobe ya buɗe, acetyl da benzoyl sunyi ƙaura
(1S,2S,3R,4S,5S,7S,8S,10R,13S)-5,10-diacetyloxy-1,2,4,7-tetrahydroxy-8,12,15,15-tetramethyl-9-oxo- 4- (phenylcarbonyloxymethyl) tricyclo[9.3.1.03,8] pentadec-11-en-13-yl
(2R, 3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino) propanoate
10,13-Bissidechainpaclitaxel
Baccatin III 13-ester tare da (2R,3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino) propanoic acid, 10-ester tare da (2S,3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino). Propanoic acid
Bugu da ƙari, rashin ƙetare iyaka ga ƙazantattun abubuwan da ke da alaƙa da paclitaxel a cikin Table 2, ba a sami fiye da 0.1% na kowane ƙazanta ɗaya ba;kuma ba fiye da 2.0% na jimlar ƙazanta ana samun su ba.
gwajin 3 (don kayan da aka lakafta kamar yadda aka samar ta hanyar tsarin haifuwa ta kwayar halitta) - Idan kayan ya bi wannan gwajin, lakabin yana nuna cewa ya dace da abubuwan da ke da alaƙa da USP Gwajin 3.
Magani A-Shirya tsaftataccen ruwan da aka lalatar da ruwa da acetonitrile (3:2).
Magani B-Shirya tacewa da kuma lalata acetonitrile.
Lokacin wayar hannu-Yi amfani da gauraya masu canji na Magani A da Magani B kamar yadda aka umurce su don tsarin Chromatographic.Yi gyare-gyare idan ya cancanta (duba Dacewar Tsarin ƙarƙashin Chromatography 621).
Maganin dacewa da tsarin-Narke USP Paclitaxel Rashin Tsabtace Cakuda RS a cikin acetonitrile, sonicating idan ya cancanta, don samun maganin ciwon sananniya na kusan 1 MG kowace ml.
Daidaitaccen bayani-Narke adadin USP Paclitaxel RS daidai gwargwado a cikin acetonitrile, sonicating idan ya cancanta, don samun maganin ciwon sananniya na kusan 1 MG kowace ml.
Maganin gwajin gwaji-Canja wurin kusan MG 10 na Paclitaxel, daidaitaccen auna, zuwa faifan girma na 10-ml.Narkar da kuma tsoma tare da acetonitrile zuwa girma, sonicating idan ya cancanta, da haɗuwa.
Tsarin Chromatographic (duba Chromatography 621) - Na'urar chromatograph na ruwa an sanye shi da na'urar ganowa 227-nm da ginshiƙin 4.6-mm × 15-cm wanda ya ƙunshi 3-µm tattara L1.Matsakaicin kwarara shine kusan 1.2 ml a minti daya.An tsara chromatograph kamar haka.
Lokaci (minti) Magani A (%) Magani B (%) Elution
0-28 100 0 masu zaman kansu
28-33 100®98 0®2 layin layi
33–58 98®10 2®90 layin layi
58-60 10 90 masu bautar gumaka
60-63 10®100 90®0 layin layi
63-70 100 0 isocraticChromatograph da tsarin dacewa da tsarin, da rikodin mafi girman martani kamar yadda aka tsara don Tsari: ƙuduri, R, tsakanin paclitaxel da analog na benzyl bai ƙasa da 1.8 ba.Chromatograph the Standard bayani, da rikodin mafi girman martani kamar yadda aka ba da umarni don Tsari: madaidaicin ma'auni don maimaita alluran bai wuce 2.0% ba.[bayanin kula-Don manufar gano kololuwa, ana ba da kusan lokutan riƙewa na dangi a cikin Teburin 3. An auna lokutan riƙewar dangi tare da Paclitaxel.]
Table 3
Iyakacin Lokacin Riƙe Sunan (%)
Analog na Propyl 1 0.54 0.2
Cephalomannine (Magungunan da ke da alaƙa da Paclitaxel A) 0.76 0.5
sec-Butyl analog2 0.81 0.2
n-Butyl analog3 0.89 0.1
Benzyl analog 1.10 0.4
Baccatin VI 1.23 0.2
Pentyl analog 1.31 0.2
7-Epipaclitaxel 1.51 0.4
1 Ana sanya sunan sinadarai mai zuwa ga abin da ke da alaƙa Propyl analog:Baccatin III 13-ester tare da (2R,3S) -3-butanoylamino-2-hydroxy-3-phenylpropanoic acid.
2 Ana sanya sunan sinadarai mai zuwa ga mahaɗin da ke da alaƙa sec-Butyl analog:Baccatin III 13-ester tare da (2R,3S) -2-hydroxy-3- (2-methylbutanoylamino) -3-phenylpropanoic acid.
3 Sunan sinadarai mai zuwa an sanya shi zuwa wani abu mai alaƙa n-Butyl analog:Baccatin III 13-ester tare da (2S,3S) -2-hydroxy-3-(pentanoylamino) -3-phenylpropanoic acid.
4 Ana sanya sunan sinadarai mai zuwa ga abin da ke da alaƙa Pentyl analog: Baccatin III 13-ester tare da (2R,3S) -3-(hexanoylamino) -2-hydroxy-3-phenylpropanoic acid.
Tsari - Allurar ƙarar (kimanin 12 µL) na maganin gwajin a cikin chromatograph, yi rikodin chromatogram, da auna wuraren don duk kololuwa.Yi ƙididdige adadin kowane ƙazanta a cikin ɓangaren Paclitaxel da aka ɗauka ta dabara:
100 (ri / rU)
wanda ri ne martanin kowane mutum da kazanta;kuma rU shine jimlar wuraren duk kololuwar da aka samu daga maganin gwajin.Bugu da ƙari, rashin ƙetare iyaka don ƙazantattun abubuwan da ke da alaƙa da paclitaxel a cikin Table 3, ba a sami fiye da 0.1% na kowane ƙazanta ɗaya ba;kuma ba fiye da 2.0% na jimlar ƙazanta ana samun su ba.
Assay-
Diluent-Shirya cakuda methanol da acetic acid (200: 1).
Wayar hannu lokaci-Shirya taceccen ruwa mai tsaftataccen ruwa da acetonitrile (11:9).Yi gyare-gyare idan ya cancanta (duba Dacewar Tsarin ƙarƙashin Chromatography 621).
Standard shirye-shirye-Narke, ta yin amfani da sonication idan ya cancanta, an daidai auna adadin USP Paclitaxel RS a diluent, da kuma tsarma quantitatively, kuma stepwise idan ya cancanta, tare da diluent don samun wani bayani ciwon san maida hankali game da 1 MG da ml.
Shirye-shiryen Assay-Canja wurin kusan MG 10 na Paclitaxel, daidaitaccen auna, zuwa flask mai girma na 10-ml.Narke a cikin Diluent, ta amfani da sonication idan ya cancanta, tsoma tare da Diluent zuwa girma, da kuma haɗuwa.
Tsarin Chromatographic (duba Chromatography <621>) -Chromatograph na ruwa yana sanye da na'urar ganowa 227-nm da ginshiƙin 4.6-mm × 25-cm wanda ya ƙunshi 5-µm tattara L43.Matsakaicin kwarara shine kusan 1.5 ml a minti daya.Chromatograph da Daidaitaccen shiri, da rikodin mafi girman martani kamar yadda aka ba da umarni don Tsari: ma'aunin wutsiya yana tsakanin 0.7 da 1.3;kuma madaidaicin ma'auni na dangi don kwafin injections bai wuce 1.5%.
Tsari-Na dabam allura daidai juzu'i (kimanin 10 µL) na daidaitaccen shiri da shirye-shiryen Assay a cikin chromatograph, yi rikodin chromatograms, da auna wuraren don manyan kololuwa.Yi ƙididdige adadin, a cikin MG, na C47H51NO14 a cikin ɓangaren Paclitaxel da aka ɗauka ta dabara:
10C (rU / rS)
wanda C shine maida hankali, a cikin MG da ml, na USP Paclitaxel RS a cikin Shirye-shiryen Standard;da rU da rS sune mafi girman martani ga paclitaxel da aka samu daga shirye-shiryen Assay da Daidaitaccen shiri, bi da bi.