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-imwe 6, 12b-diacetate, 12-benzoate, 9-ester ine (2R,3S)-N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel ine kwete pasi pe97.0 muzana uye kwete kupfuura 102.0 muzana yeC47H51NO14, yakaverengerwa pane anhydrous, solvent-isina hwaro.
[Kuchenjerera-Paclitaxel is cytotoxic.Kungwarira kukuru kunofanirwa kutorwa kudzivirira kupinza zvidimbu zvePaclitaxel uye kufumura ganda kwairi.]
Packaging uye kuchengetedza-Chengetedza mumidziyo yakasimba, isingagadzike chiedza, uye chengetedza pane inodzorwa tembiricha yekamuri.
Labeling-Kunyora kunoratidza mhando yemaitiro anoshandiswa kugadzira zvinhu uye Related makomponi bvunzo iyo inoteedzera zvinhu.
USP Reference mwero <11>-
USP Endotoxin RS
USP Paclitaxel RS Dzvanya kuti uone Chimiro
USP Paclitaxel Inoenderana Musanganiswa A RS
Cephalomannine.
USP Paclitaxel Inoenderana Musanganiswa B RS
10-Deacetyl-7-Epipaclitaxel.
USP Paclitaxel Impurity Mixture RS
Kusanganiswa kwePaclitaxel uye zvinotevera zvinosanganiswa: propyl analog, cephalomannine, sec-butyl analog, n-butyl analog, benzyl analog, baccatin VI, pentyl analog, uye 7-epipaclitaxel.
Identification-
A: Infrared Absorption <197K>.
B: Nguva yekuchengeta yepamusoro-soro muchromatogram yeAssay kugadzirira inoenderana neiyo mukromatogram yeStandard gadziriro, sezvakawanikwa muAssay.
Kutenderera kwakananga 781S: pakati pe49.0 ne55.0 pa20, yakaverengerwa pane anhydrous, solvent-isina hwaro.
Mhinduro yekuedza: 10 mg pa mL, mu methanol.
Microbial enumeration tests <61> uye Miedzo yezvipembenene zvakatsanangurwa <62>-The total aerobic microbial count haipfuure 100 cfu per g.Inosangana nezvinodiwa zvekuedzwa kwekushaikwa kweStaphylococcus aureus, Pseudomonas aeruginosa, Salmonella marudzi, uye Escherichia coli.
Bhakitiriya endotoxins 85-Iyo haina kupfuura 0.4 USP Endotoxin Unit pamg ye paclitaxel.
Mvura, Method Ic <921>: kwete kupfuura 4.0%.
Residue pakudzima <281>: kwete kupfuura 0.2%.
Heavy metals, Nzira II <231>: 0.002%.
Related Compounds-
bvunzo 1 (yemidziyo yakanyorwa seyakaparadzaniswa kubva kune yakasikwa)-Kana iyo inoenderana nebvunzo iyi, iyo yakanyorwa inoratidza kuti inosangana neUSP Inoenderana makomisheni Test 1.
Diluent-Gadzirira sezvakarairwa muAssay.
Solution A-Gadzirira yakasefa uye degassed acetonitrile.
Mhinduro B-Gadzirira mvura yakasvibiswa uye yakasvibiswa.
Nharembozha chikamu-Shandisa akasiyana musanganiswa weSolution A uye Solution B sekurairwa kweChromatographic system.Ita zvigadziriso kana zvichidikanwa (ona System Suitability pasi peChromatography 621).
Kukodzera kweSystem solution-Dissolve nemazvo kuyerwa huwandu hweUSP Paclitaxel Related Compound A RS uye USP Paclitaxel Related Compound B RS mumethanol kuti uwane mhinduro ine kuziva kudzika kwe 10 µg yega yega paML.Chinja 5.0 mL yemhinduro iyi kune 50-mL volumetric flask, dilue neDiluent kusvika kuhuwandu, uye sanganisa.
Standard solution-Dissolve, nerubatsiro rwe sonication, huremu hwakanyatsoyerwa hweUSP Paclitaxel RS mu Diluent, uye dzikisa huwandu, uye nhanho kana zvichidikanwa, neDiluent kuti uwane mhinduro ine huwandu hunozivikanwa hunosvika 5 µg per mL.
Test solution-Shandisa gadziriro yeAssay.
Chromatographic system (ona Chromatography <621>) -Iyo chromatograph yemvura inogadzirwa ne 227-nm detector uye 4.6-mm × 25-cm column ine 5-µm packing L43.Chiyero chekuyerera chinenge 2.6 mL paminiti.Iko kupisa kwembiru inochengetwa pa 30. Chromatograph inorongwa sezvinotevera.
Nguva (maminetsi) Solution A (%) Solution B (%) Elution
0–35 35 65 isocratic
35–60 35®80 65®20 linear gradient
60–70 80®35 20®65 linear gradient
70–80 35 65 isocraticChromatograph the System suitability solution, uye rekodha mhinduro dzepamusoro sekurairwa kwazvinoitwa kuProcedure: nguva dzekuchengeta dzinenge 0.78 yepaclitaxel inoenderana nekomboni A uye 0.86 yepaclitaxel ine hukama mukomboni B (inoenderana nenguva yekuchengeta paclitaxel inowanikwa kubva mhinduro yekuedza);uye chigadziriso, R, pakati pe paclitaxel ine hukama mukomboni A uye paclitaxel ine hukama mukomboni B haisi pasi pe1.0.Chromatograph iyo Yakajairwa mhinduro, uye rekodha mhinduro dzepamusoro sekurairwa kweMaitiro: chiyero chakajairwa kutsauswa kwemajekiseni anodzokorora haapfuure 2.0%.
Maitiro-Baya vhoriyamu (inenge 15 µL) yeMuedzo mhinduro muchromatograph, rekodha chromatogram, uye kuyera nzvimbo dzepamusoro-soro.Verengai muzana yekusachena kwega kwega muchikamu chePaclitaxel chakatorwa neformula:
100(Chishanu / rU)
umo F ndiyo inopindirana yekupindura peak yega yega yekusachena (ona Tafura 1 yehukoshi);ri ndiyo nzvimbo yepamusoro yekusachena kwega kwega;uye rU ndiyo nzvimbo yepamusoro ye paclitaxel.
Tafura 1
Relative Retention Time Relative Response Factor (F) Name Limit (%)
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 (Paclitaxel inoenderana nemubatanidzwa A) a11
0.78 1.26 2'',3''-Dihydrocephalomanine a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel inoenderana nemubatanidzwa B) 0.5
1.10 1.00 Benzyl analogi3 b12
1.10 1.00 3'',4''-Dehydropaclitaxel C b22
1.40 1.00 7-Epicephalomannine 0.3
1.85 1.00 7-Epipaclitaxel 0.5
1 Sarudzo inogona kunge isina kukwana pazvikwiriso izvi, zvichienderana nehuwandu huripo;huwandu hwea1 uye a2 haupfuuri 0.5%.
2 Chisungo chinogona kunge chisina kukwana pazvikwiriso izvi, zvichienderana nehuwandu hwehuwandu huripo;nhamba ye b1 uye b2 haisi kupfuura 0.5%.
3 Iri rinotevera remakemikari zita rinopiwa kune yakabatana inosanganiswa, benzyl analog:Baccatin III 13-ester ine (2R,3S) -2-hydroxy-3-phenyl-3-(2-phenylacetylamino)propanoic acid.
Pamusoro pekusapfuudza miganho yetsvina ine hukama ne paclitaxel muTebhura 1, isingasviki 0.1% yeimwe imwe tsvina inowanikwa;uye kwete kupfuura 2.0% yetsvina yose inowanikwa.
bvunzo 2 (yezvinhu zvakanyorwa semisynthetic process)— Kana zvinhu zvacho zvichienderana nebvunzo iyi, kunyora kunoratidza kuti kunosangana neUSP Inoenderana makomboni Test 2.
Diluent-Shandisa acetonitrile.
Mhinduro A-Shandisa yakasvibiswa uye yakasvibiswa musanganiswa wemvura uye acetonitrile (3: 2).
Solution B-Shandisa yakasefa uye degassed acetonitrile.
Nharembozha chikamu-Shandisa akasiyana musanganiswa weSolution A uye Solution B sekurairwa kweChromatographic system.Ita zvigadziriso kana zvichidikanwa (ona System Suitability pasi peChromatography 621).
Kukodzera kweSystem solution-Dissolve huremu hwakayerwa nemazvo eUSP Paclitaxel RS uye USP Paclitaxel Related Compound B RS in Diluent, kuzunungusa uye sonicating kana zvichidikanwa, kuwana mhinduro ine zvinozivikanwa zvekuisa nezve 0.96 mg uye 0.008 mg per mL, zvichiteerana.
Muedzo mhinduro-Shandura nezve 10 mg yePaclitaxel, yakanyatso kuyerwa, kune 10-mL volumetric flask, nyunguduka mukati uye dilute neDiluent kusvika kuhuwandu, kuzunungusa uye sonicating kana zvichidikanwa, uye sanganisa.
Chromatographic system (ona Chromatography 621)— Iyo chromatograph yemvura ine 227-nm detector uye 4.6-mm × 15-cm column ine 3-µm packing L1.Chiyero chekuyerera chinenge 1.2 mL paminiti.Iko kupisa kwembiru inochengetwa pa 35. Chromatograph inorongwa sezvinotevera.
Nguva (maminetsi) Solution A (%) Solution B (%) Elution
0-20 100 0 isocratic
20-60 100®10 0®90 linear gradient
60-62 10®100 90®0 linear gradient
62-70 100 0 isocraticChromatograph the System suitability solution, uye rekodha mhinduro dzepamusoro sezvakarongwa kuProcedure: nguva dzekuchengetedza dzinenge dzinenge 0.94 dzepaclitaxel dzine chokuita nekomboni B uye 1.0 ye paclitaxel;iyo resolution, R, pakati pe paclitaxel inoenderana nekamu B uye paclitaxel haisi pasi pe1.2;uye kutsauswa kwakayerwa kwemajekiseni ekudzokorora hakupfuuri 2.0%.
Maitiro-Kuparura jekiseni mavhoriyamu akaenzana (angangoita 15 µL) eDiluent uye Muyedzo mhinduro mukromatograph, rekodha machromatogram, uye kuyera nzvimbo dzepamusoro pese.Rega chero mapeaks nekuda kweDiluent.Verengai muzana yekusachena kwega kwega muchikamu chePaclitaxel chakatorwa neformula:
100(Chishanu / rs)
umo F ndiyo inopindirana yemhinduro yekusachena kwega kwega (ona Tafura 2 yehukoshi);ri ndiyo nzvimbo yepamusoro yekusachena kwega kwega kunowanikwa kubva kuMubvunzo mhinduro;uye rs ndiyo hwerengedzo yenzvimbo dzepamusoro pese dzakawanikwa kubva muyedzo mhinduro.
Tafura 2
Relative Retention Time Relative Response Factor (F) Name Limit (%)
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 mhete yakavhurwa, acetyl uye benzoyl yakatama2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel ine chekuita 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 Sarudzo inogona kunge isina kukwana pazvikwiriso izvi, zvichienderana nehuwandu huripo;huwandu hwe x1, x2, uye x3 haupfuuri 0.4%.
2 Mazita emakemikari anotevera anopihwa kune ane hukama makomisheni Photodegradant;Oxetane mhete yakavhurwa, acetyl uye benzoyl zvakatama;uye 10,13-Bissidechainpaclitaxel:
Photodegradant
(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 mhete yakavhurwa, acetyl uye benzoyl zvakatama
(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 ine (2R,3S) -2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoic acid, 10-ester ine (2S,3S) -2-hydroxy-3-phenyl-3-(phenylcarbonylamino propanoic acid
Pamusoro pekusapfuudza miganho yekusachena kwakabatana ne paclitaxel muTebhu 2, kwete kupfuura 0.1% yeimwe imwe tsvina inowanikwa;uye kwete kupfuura 2.0% yetsvina yose inowanikwa.
bvunzo 3 (yezvinhu zvakanyorwa sezvinogadzirwa nechirimwa sero kuvirisa)— Kana zvinhu zvacho zvichienderana nebvunzo iyi, manyorerwo anoratidza kuti anosangana neUSP Inoenderana makomboni Test 3.
Mhinduro A-Gadzirira musanganiswa wakanatswa uye wakasvibiswa wemvura uye acetonitrile (3: 2).
Mhinduro B-Gadzirira yakasefa uye degassed acetonitrile.
Nharembozha chikamu-Shandisa akasiyana musanganiswa weSolution A uye Solution B sekurairwa kweChromatographic system.Ita zvigadziriso kana zvichidikanwa (ona System Suitability pasi peChromatography 621).
System suitability solution-Dissolve USP Paclitaxel Impurity Mixture RS mu acetonitrile, sonicating kana zvichidiwa, kuti uwane mhinduro ine ruzivo rwakanyanya rwe 1 mg per mL.
Suluhu yakajairwa-Dissolve iyo yakanyatso kuyerwa huwandu hweUSP Paclitaxel RS muacetonitrile, sonicating kana zvichidikanwa, kuwana mhinduro ine fungidziro inozivikanwa yeanenge 1 mg per mL.
Muedzo wemhinduro-Kutamisa nezve 10 mg yePaclitaxel, yakanyatso kuyerwa, kune 10-mL volumetric flask.Dissolve in and diluted with acetonitrile to volume, sonicating kana zvichidiwa, uye sanganisa.
Chromatographic system (ona Chromatography 621)— Iyo chromatograph yemvura ine 227-nm detector uye 4.6-mm × 15-cm column ine 3-µm packing L1.Chiyero chekuyerera chinenge 1.2 mL paminiti.Iyo chromatograph yakarongedzwa sezvinotevera.
Nguva (maminetsi) Solution A (%) Solution B (%) Elution
0-28 100 0 isocratic
28-33 100®98 0®2 linear gradient
33–58 98®10 2®90 linear gradient
58-60 10 90 isocratic
60-63 10®100 90®0 linear gradient
63-70 100 0 isocraticChromatograph iyo Sistimu yakakodzera mhinduro, uye rekodha mhinduro dzepamusoro sekurairwa kwaProcedure: sarudzo, R, pakati pepaclitaxel nebenzyl analogi haisi pasi pe1.8.Chromatograph iyo Yakajairwa mhinduro, uye rekodha mhinduro dzepamusoro sekurairwa kweMaitiro: chiyero chakajairwa kutsauswa kwemajekiseni anodzokorora haapfuure 2.0%.[chiziviso-Nechinangwa chekuzivikanwa kwepamusoro-soro, nguva dzinofungidzirwa dzekuchengetedza dzinopihwa muTebhurari 3. Nguva dzekuchengeta dzinoyerwa maringe nePaclitaxel.]
Tafura 3
Zita Relative Retention Time Limit (%)
Propyl analog1 0.54 0.2
Cephalomannine (Paclitaxel yakabatana musanganiswa 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 analog4 1.31 0.2
7-Epipaclitaxel 1.51 0.4
1 Iri rinotevera zita remakemikari rinopihwa kune yakabatana kompani Propyl analogi:Baccatin III 13-ester ine (2R,3S) -3-butanoylamino-2-hydroxy-3-phenylpropanoic acid.
2 Iro zita remakemikari rinotevera rinopiwa kune yakabatana chidimbu sec-Butyl analog: Baccatin III 13-ester ne (2R, 3S) -2-hydroxy-3- (2-methylbutanoylamino) -3-phenylpropanoic acid.
3 Iro zita remakemikari rinotevera rinopiwa kune yakabatana inosanganiswa n-Butyl analog:Baccatin III 13-ester ne (2S,3S) -2-hydroxy-3-(pentanoylamino) -3-phenylpropanoic acid.
4 Iri rinotevera remakemikari zita rinopihwa kune yakabatana kompani Pentyl analogi:Baccatin III 13-ester ine (2R,3S) -3-(hexanoylamino) -2-hydroxy-3-phenylpropanoic acid.
Maitiro-Baya vhoriyamu (inenge 12 µL) yeMuedzo mhinduro muchromatograph, rekodha chromatogram, uye kuyera nzvimbo dzepamusoro pese.Verengai muzana yekusachena kwega kwega muchikamu chePaclitaxel chakatorwa neformula:
100(ri / rU)
umo ri iri mhinduro yekusachena kwega kwega;uye rU ndiyo hwerengedzo yenzvimbo dzepamusoro pese dzakawanikwa kubva kuMubvunzo mhinduro.Pamusoro pekusapfuudza miganho yekusachena kwakabatana ne paclitaxel muTebhu 3, kwete kupfuura 0.1% yeimwe imwe tsvina inowanikwa;uye kwete kupfuura 2.0% yetsvina yose inowanikwa.
Kuongorora-
Diluent-Gadzirira musanganiswa we methanol uye acetic acid (200: 1).
Nharembozha-Gadzirira musanganiswa wakanatswa uye wakasvibiswa wemvura uye acetonitrile (11: 9).Ita zvigadziriso kana zvichidikanwa (ona System Suitability pasi peChromatography 621).
Kugadzirira kwakajairwa-Dissolve, uchishandisa sonication kana zvichidikanwa, huremu hwakanyatsoyerwa hweUSP Paclitaxel RS mu Diluent, uye dilute quantitatively, uye nhanho kana zvichidikanwa, neDiluent kuti uwane mhinduro ine chiyero chinozivikanwa che 1 mg per mL.
Kugadzirira kweAssay-Kuendesa nezve 10 mg yePaclitaxel, yakanyatsoyerwa, kune 10-mL volumetric flask.Dissolve in Diluent, uchishandisa sonication kana zvichidikanwa, dilue neDiluent kusvika kuhuwandu, uye sanganisa.
Chromatographic system (ona Chromatography <621>) -Iyo chromatograph yemvura inogadzirwa ne 227-nm detector uye 4.6-mm × 25-cm column ine 5-µm packing L43.Chiyero chekuyerera chinenge 1.5 mL paminiti.Chromatograph the Standard gadziriro, uye rekodha mhinduro dzepamusoro sekurairwa kweMaitiro: iyo tailing factor iri pakati pe0.7 ne1.3;uye kutsauswa kwakajairwa kwemajekiseni ekudzokorora hakupfuuri 1.5%.
Maitiro-Kuparura jekiseni mavhoriyamu akaenzana (angangoita gumi µL) eChimiro gadziriro uye gadziriro yeAssay muchromatograph, rekodha machromatogram, uye kuyera nzvimbo dzepamusoro-soro.Verenga huwandu, mu mg, hweC47H51NO14 muchikamu chePaclitaxel chakatorwa neformula:
10C(rU / rS)
umo C ndiyo inosungirirwa, mu mg per mL, ye USP Paclitaxel RS muChirongwa chekugadzirira;uye rU nerS ndiwo mhinduro dzepamusoro dzepaclitaxel dzakawanikwa kubva mukugadzirira kweAssay uye gadziriro yeStandard, zvichiteerana.