Paclitaxel (Taxol) CAS 33069-62-4 Kev Ntsuam Xyuas (HPLC) 97.0 ~ 102.0%

Paclitaxel
C47H51NO14 853.91
Benzenepropanoic acid, -(benzoylamine)--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-ib 6, 12b-diacetate, 12-benzoate, 9-ester nrog (2R,3S)-N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel muaj tsis pub tsawg tshaj 97.0 feem pua ​​thiab tsis ntau tshaj 102.0 feem pua ​​ntawm C47H51NO14, xam nyob rau hauv lub anhydrous, hnyav-dawb lub hauv paus.
[Ceev faj-Paclitaxel yog cytotoxic.Kev saib xyuas zoo yuav tsum tau coj los tiv thaiv kev nqus cov pa ntawm Paclitaxel thiab nthuav tawm cov tawv nqaij rau nws.]
Ntim thiab khaws cia-Txuag hauv cov thawv nruj, lub teeb-tiv taus, thiab khaws cia ntawm chav tsev kub.
Labeling-Lub labeling qhia txog hom txheej txheem siv los tsim cov khoom siv thiab cov khoom sib txuas sib txuas nrog cov khoom ua raws.
USP Reference cov qauv <11>-
Tom ntej: USP Endotoxin RS
USP Paclitaxel RS Nyem rau Saib Cov Qauv
USP Paclitaxel Related Compound A RS
Cephalomannine.
USP Paclitaxel Related Compound B RS
10-Deacetyl-7-Epipaclitaxel.
USP Paclitaxel Impurity Mixture RS
Kev sib xyaw ntawm Paclitaxel thiab cov khoom sib txuas hauv qab no: propyl analog, cephalomannine, sec-butyl analog, n-butyl analog, benzyl analog, baccatin VI, pentyl analog, thiab 7-epipaclitaxel.
Kev txheeb xyuas-
A: Infrared Absorption <197K>.
B: Lub sijhawm khaws cia ntawm lub ncov loj hauv chromatogram ntawm Assay kev npaj sib raug rau qhov ntawd nyob rau hauv chromatogram ntawm Standard npaj, raws li tau txais hauv Assay.
Kev sib hloov tshwj xeeb 781S: nruab nrab ntawm 49.0 thiab 55.0 ntawm 20, suav ntawm cov dej tsis muaj dej, hnyav-dawb.
Test tov: 10 mg ib mL, hauv methanol.
Kev ntsuam xyuas microbial enumeration <61> thiab Kev Ntsuas rau cov kab mob uas tau teev tseg <62>-Cov suav aerobic microbial tag nrho tsis pub tshaj 100 cfu ib g.Nws ua tau raws li qhov yuav tsum tau ua ntawm kev sim rau qhov tsis muaj Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella hom, thiab Escherichia coli.
Cov kab mob endotoxins 85-Nws muaj tsis ntau tshaj 0.4 USP Endotoxin Unit ib mg ntawm paclitaxel.
Dej, Txoj Kev Ic <921>: tsis ntau tshaj 4.0%.
Residue ntawm ignition <281>: tsis ntau tshaj 0.2%.
Cov hlau hnyav, Txoj Kev II <231>: 0.002%.
Related Compounds-
xeem 1 (rau cov ntaub ntawv sau tseg raws li cais los ntawm tej yam ntuj tso qhov chaw)-Yog hais tias cov khoom ua raws li qhov kev xeem no, daim ntawv lo qhia tias nws ua tau raws li USP Related compounds Test 1.
Diluent-Prepare raws li qhia nyob rau hauv Assay.
Tshuaj A-Npaj lim thiab degassed acetonitrile.
Tshuaj B-Npaj lim thiab degassed dej.
Txawb theem-Siv sib txawv sib txawv ntawm cov tshuaj A thiab tshuaj B raws li qhia rau Chromatographic system.Hloov kho yog tias tsim nyog (saib System Suitability hauv Chromatography 621).
System suitability solution-Dissolve kom raug hnyav npaum li cas ntawm USP Paclitaxel Related Compound A RS thiab USP Paclitaxel Related Compound B RS hauv methanol kom tau txais cov tshuaj uas muaj kev paub ntau txog 10 µg ntawm txhua ib mL.Hloov 5.0 mL ntawm cov tshuaj no mus rau 50-mL ntim ntim, dilute nrog Diluent rau ntim, thiab sib tov.
Standard tov-Dissolve, nrog rau kev pab los ntawm sonication, ib tug meej luj kom muaj nuj nqis ntawm USP Paclitaxel RS nyob rau hauv Diluent, thiab dilute quantitatively, thiab stepwise yog hais tias tsim nyog, nrog Diluent kom tau ib tug tov muaj ib tug paub concentration ntawm txog 5 µg ib mL.
Test solution-Siv qhov Assay npaj.
Chromatographic system (saib Chromatography <621>)-Cov kua chromatograph yog nruab nrog 227-nm detector thiab 4.6-mm × 25-cm kem uas muaj 5-µm packing L43.Tus nqi ntws yog li 2.6 mL ib feeb.Lub kem kub yog tswj ntawm 30. Lub chromatograph yog programmed raws li nram no.
Sijhawm (feeb) Tshuaj A (%) Tshuaj B (%) Elution
0–35 35 65 ib
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, thiab sau cov lus teb siab kawg raws li qhia rau Cov Txheej Txheem: lub sij hawm tuav tus txheeb ze yog li ntawm 0.78 rau paclitaxel ntsig txog compound A thiab 0.86 rau paclitaxel ntsig txog B (kwv yees rau lub sijhawm khaws cia rau paclitaxel tau los ntawm Test daws);thiab kev daws teeb meem, R, nruab nrab ntawm paclitaxel ntsig txog compound A thiab paclitaxel ntsig txog B tsis tsawg dua 1.0.Chromatograph tus qauv kev daws teeb meem, thiab sau cov lus teb siab tshaj plaws raws li qhia rau Kev Ua Haujlwm: tus qauv sib txawv ntawm qhov sib txawv rau kev txhaj tshuaj tsis ntau tshaj 2.0%.
Cov txheej txheem-Txhim ib lub ntim (kwv yees li 15 µL) ntawm cov tshuaj Test rau hauv cov chromatograph, sau cov chromatogram, thiab ntsuas cov cheeb tsam rau cov peaks loj.Xam cov feem pua ​​​​ntawm txhua qhov impurity hauv ib feem ntawm Paclitaxel coj los ntawm cov mis:
100 (Fri / rU)
nyob rau hauv uas F yog tus txheeb ze teb qhov tseem ceeb rau txhua impurity ncov (saib Table 1 rau qhov tseem ceeb);ri yog thaj chaw ncov rau txhua tus neeg impurity;thiab rU yog qhov chaw siab tshaj rau paclitaxel.
Table 1
Tus txheeb ze Retention Time Relative Response Factor (F) Lub Npe Txwv (%)
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 ntsig txog compound A) a11
0.78 1.26 2'', 3''-Dihydrocephalomannine a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel ntsig txog compound B) 0.5
1.10 1.00 Benzyl analog3 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 Kev daws teeb meem yuav ua tsis tiav rau cov ncov no, nyob ntawm seb tus nqi txheeb ze tam sim no;qhov sum ntawm a1 thiab a2 tsis ntau tshaj 0.5%.
2 Kev daws teeb meem yuav ua tsis tiav rau cov ncov no, nyob ntawm seb tus nqi txheeb ze tam sim no;qhov sib npaug ntawm b1 thiab b2 tsis ntau tshaj 0.5%.
3 Lub npe tshuaj hauv qab no yog muab rau cov khoom sib txuas, benzyl analog: Baccatin III 13-ester nrog (2R,3S)-2-hydroxy-3-phenyl-3-(2-phenylacetylamino) propanoic acid.
Ntxiv rau qhov tsis pub tshaj qhov txwv rau paclitaxel ntsig txog impurities hauv Table 1, tsis pub ntau tshaj 0.1% ntawm lwm yam impurity ib leeg;thiab tsis pub ntau tshaj 2.0% ntawm tag nrho cov impurities pom.
xeem 2 (rau cov ntaub ntawv sau npe raws li tsim los ntawm ib tug semisynthetic txheej txheem) — Yog hais tias cov khoom ua raws li qhov kev xeem no, daim ntawv lo qhia tias nws ua tau raws li USP Related compounds Test 2.
Diluent-Siv acetonitrile.
Kev daws A-Siv cov lim dej thiab degassed sib tov ntawm dej thiab acetonitrile (3: 2).
Kev daws B-Siv lim thiab degassed acetonitrile.
Txawb theem-Siv sib txawv sib txawv ntawm cov tshuaj A thiab tshuaj B raws li qhia rau Chromatographic system.Hloov kho yog tias tsim nyog (saib System Suitability hauv Chromatography 621).
System suitability solution-Dissolve kom raug hnyav npaum li cas ntawm USP Paclitaxel RS thiab USP Paclitaxel Related Compound B RS hauv Diluent, co thiab sonicating yog tias tsim nyog, kom tau txais cov tshuaj uas muaj kev paub ntau txog 0.96 mg thiab 0.008 mg ib mL, feem.
Kuaj cov tshuaj-Hloov txog 10 mg ntawm Paclitaxel, raug hnyav, mus rau 10-mL ntim ntim, yaj hauv thiab dilute nrog Diluent rau ntim, co thiab sonicating yog tias tsim nyog, thiab sib tov.
Chromatographic system (saib Chromatography 621)- Cov kua chromatograph yog nruab nrog 227-nm detector thiab 4.6-mm × 15-cm kem uas muaj 3-µm packing L1.Tus nqi ntws yog li 1.2 mL ib feeb.Lub kem kub yog tswj ntawm 35. Lub chromatograph yog programmed raws li nram no.
Sijhawm (feeb) Tshuaj A (%) Tshuaj 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, thiab sau cov lus teb ncov raws li qhia rau Cov Txheej Txheem: lub sij hawm tuav tus txheeb ze yog li ntawm 0.94 rau paclitaxel ntsig txog B thiab 1.0 rau paclitaxel;qhov kev daws teeb meem, R, nruab nrab ntawm paclitaxel ntsig txog compound B thiab paclitaxel tsis tsawg dua 1.2;thiab tus txheeb ze tus qauv sib txawv rau kev txhaj tshuaj replicate tsis ntau tshaj 2.0%.
Cov txheej txheem-Kev txhaj tshuaj sib npaug (kwv yees li 15 µL) ntawm Diluent thiab Test tov rau hauv chromatograph, sau cov chromatograms, thiab ntsuas qhov chaw rau tag nrho cov peaks.Disregard tej peaks vim Diluent.Xam cov feem pua ​​​​ntawm txhua qhov impurity hauv ib feem ntawm Paclitaxel coj los ntawm cov mis:
100 (Fri / rs)
nyob rau hauv uas F yog tus txheeb ze teb qhov tseem ceeb rau txhua impurity (saib Table 2 rau qhov tseem ceeb);ri yog thaj chaw ncov rau txhua qhov impurity tau los ntawm Kev Ntsuas Kev daws;thiab rs yog cov sum ntawm cov cheeb tsam ntawm tag nrho cov peaks tau los ntawm Test daws.
Rooj 2
Tus txheeb ze Retention Time Relative Response Factor (F) Lub Npe Txwv (%)
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 nplhaib qhib, acetyl thiab benzoyl migrated2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel ntsig txog compound 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 Kev daws teeb meem yuav ua tsis tiav rau cov ncov no, nyob ntawm seb tus nqi txheeb ze tam sim no;cov sum ntawm x1, x2, thiab x3 tsis ntau tshaj 0.4%.
2 Cov npe tshuaj hauv qab no raug muab rau cov khoom sib txuas Photodegradant;Oxetane nplhaib qhib, acetyl thiab benzoyl migrated;thiab 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 nplhaib qhib, acetyl thiab benzoyl migrated
(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 nrog (2R,3S)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoic acid, 10-ester nrog (2S,3S)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino ) propanoic acid
Ntxiv rau qhov tsis pub tshaj qhov txwv rau paclitaxel ntsig txog impurities hauv Table 2, tsis pub ntau tshaj 0.1% ntawm lwm yam impurity ib leeg;thiab tsis pub ntau tshaj 2.0% ntawm tag nrho cov impurities pom.
xeem 3 (rau cov ntaub ntawv sau npe raws li tsim los ntawm cov nroj tsuag cell fermentation txheej txheem) — Yog hais tias cov khoom ua raws li qhov kev xeem no, daim ntawv lo qhia tias nws ua tau raws li USP Related compounds Test 3.
Kev daws A-Npaj lim thiab degassed sib tov ntawm dej thiab acetonitrile (3: 2).
Tshuaj B-Npaj lim thiab degassed acetonitrile.
Txawb theem-Siv sib txawv sib txawv ntawm cov tshuaj A thiab tshuaj B raws li qhia rau Chromatographic system.Hloov kho yog tias tsim nyog (saib System Suitability hauv Chromatography 621).
System suitability solution-Dissolve USP Paclitaxel Impurity Mixture RS nyob rau hauv acetonitrile, sonicating yog tias tsim nyog, kom tau txais ib qho kev daws teeb meem uas paub txog 1 mg ib mL.
Standard tov-Dissolve ib tug meej luj kom muaj nuj nqis ntawm USP Paclitaxel RS nyob rau hauv acetonitrile, sonicating yog tsim nyog, kom tau txais ib tug paub txog concentration ntawm txog 1 mg ib mL.
Kev ntsuas tshuaj-Hloov txog 10 mg ntawm Paclitaxel, ntsuas qhov tseeb, mus rau 10-mL ntim ntim.Dissolve nyob rau hauv thiab dilute nrog acetonitrile rau ntim, sonicating yog tsim nyog, thiab sib tov.
Chromatographic system (saib Chromatography 621)- Cov kua chromatograph yog nruab nrog 227-nm detector thiab 4.6-mm × 15-cm kem uas muaj 3-µm packing L1.Tus nqi ntws yog li 1.2 mL ib feeb.Lub chromatograph yog programmed raws li hauv qab no.
Sijhawm (feeb) Tshuaj A (%) Tshuaj 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 ib
60-63 10®100 90®0 linear gradient
63-70 100 0 isocraticChromatograph qhov System haum rau kev daws teeb meem, thiab sau cov lus teb siab kawg raws li tau qhia rau Cov Txheej Txheem: kev daws teeb meem, R, ntawm paclitaxel thiab benzyl analog tsis tsawg dua 1.8.Chromatograph tus qauv kev daws teeb meem, thiab sau cov lus teb siab tshaj plaws raws li qhia rau Kev Ua Haujlwm: tus qauv sib txawv ntawm qhov sib txawv rau kev txhaj tshuaj tsis ntau tshaj 2.0%.[ceeb toom—Rau lub hom phiaj ntawm kev txheeb xyuas qhov siab tshaj plaws, kwv yees kwv yees lub sij hawm khaws cia yog muab rau hauv Table 3. Lub sij hawm tuav tus txheeb ze raug ntsuas piv rau Paclitaxel.]
Table 3
Lub Npe Lub Sijhawm Retention Limit (%)
Propyl analog1 0.54 0.2
Cephalomannine (Paclitaxel ntsig txog compound 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 Cov npe tshuaj hauv qab no tau muab rau cov khoom sib txuas Propyl analog: Baccatin III 13-ester nrog (2R,3S)-3-butanoylamino-2-hydroxy-3-phenylpropanoic acid.
2 Lub npe tshuaj hauv qab no yog muab rau cov khoom sib txuas sec-Butyl analog: Baccatin III 13-ester nrog (2R,3S)-2-hydroxy-3-(2-methylbutanoylamino)-3-phenylpropanoic acid.
3 Lub npe tshuaj hauv qab no tau muab rau cov khoom sib txuas n-Butyl analog: Baccatin III 13-ester nrog (2S,3S)-2-hydroxy-3-(pentanoylamino)-3-phenylpropanoic acid.
4 Lub npe tshuaj hauv qab no yog muab rau cov khoom sib txuas Pentyl analog: Baccatin III 13-ester nrog (2R,3S)-3-(hexanoylamino)-2-hydroxy-3-phenylpropanoic acid.
Cov txheej txheem-Txhim ib lub ntim (kwv yees li 12 µL) ntawm cov tshuaj Test rau hauv chromatograph, sau cov chromatogram, thiab ntsuas qhov chaw rau tag nrho cov peaks.Xam cov feem pua ​​​​ntawm txhua qhov impurity hauv ib feem ntawm Paclitaxel coj los ntawm cov mis:
100 hli (ri / rU)
nyob rau hauv uas ri yog cov lus teb ntawm txhua tus neeg impurity;thiab rU yog cov sum ntawm cov cheeb tsam ntawm tag nrho cov peaks tau los ntawm Test tov.Ntxiv rau qhov tsis pub tshaj qhov txwv rau paclitaxel ntsig txog impurities hauv Table 3, tsis pub ntau tshaj 0.1% ntawm lwm yam impurity ib leeg;thiab tsis pub ntau tshaj 2.0% ntawm tag nrho cov impurities pom.
Assay-
Diluent-Npaj sib tov ntawm methanol thiab acetic acid (200: 1).
Txawb theem-Npaj lim thiab degassed sib tov dej thiab acetonitrile (11:9).Hloov kho yog tias tsim nyog (saib System Suitability hauv Chromatography 621).
Standard npaj-Dissolve, siv sonication yog hais tias tsim nyog, ib tug meej luj kom muaj nuj nqis ntawm USP Paclitaxel RS nyob rau hauv Diluent, thiab dilute quantitatively, thiab stepwise yog tias tsim nyog, nrog Diluent kom tau ib tug tov muaj ib tug paub concentration ntawm txog 1 mg ib mL.
Kev tshuaj ntsuam xyuas-Hloov txog 10 mg ntawm Paclitaxel, ntsuas kom raug, mus rau 10-mL ntim ntim.Dissolve hauv Diluent, siv sonication yog tias tsim nyog, dilute nrog Diluent mus ntim, thiab sib tov.
Chromatographic system (saib Chromatography <621>)-Cov kua chromatograph yog nruab nrog 227-nm detector thiab 4.6-mm × 25-cm kem uas muaj 5-µm packing L43.Tus nqi ntws yog li 1.5 mL ib feeb.Chromatograph tus qauv npaj, thiab sau cov lus teb ncov raws li qhia rau Cov Txheej Txheem: tailing factor yog nruab nrab ntawm 0.7 thiab 1.3;thiab tus txheeb ze tus qauv sib txawv rau replicate txhaj tshuaj tsis ntau tshaj 1.5%.
Cov txheej txheem-Kev txhaj tshuaj sib npaug (kwv yees li 10 µL) ntawm Standard npaj thiab Assay npaj rau hauv chromatograph, sau cov chromatograms, thiab ntsuas qhov chaw rau lub ncov loj.Xam qhov ntau, hauv mg, ntawm C47H51NO14 hauv ib feem ntawm Paclitaxel coj los ntawm cov qauv:
10C (rU / rS)
nyob rau hauv uas C yog qhov concentration, nyob rau hauv mg ib mL, ntawm USP Paclitaxel RS nyob rau hauv tus txheej txheem npaj;thiab rU thiab rS yog cov lus teb siab tshaj plaws rau paclitaxel tau txais los ntawm Assay npaj thiab Standard npaj, feem.