Paclitaxel (Taxol) CAS 33069-62-4 Su'ega (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-one 6, 12b-diacetate, 12-benzoate, 9-ester ma (2R,3S) -N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel e le itiiti ifo i le 97.0 pasene ma e le sili atu i le 102.0 pasene ole C47H51NO14, fa'atatau i luga ole vai, e leai se solvent.
[Fa'aeteete-Paclitaxel e cytotoxic.E tatau ona faʻaeteete tele e puipuia ai le manavaina o vaega o le Paclitaxel ma faʻaalia le paʻu i ai.]
Fa'apipi'i ma teu-fa'asa'o i totonu o atigipusa fufusi, fa'amalama, ma teu i le vevela o le potu.
Fa'ailoga-O le fa'ailoga o lo'o fa'aalia ai le ituaiga o fa'agasologa o lo'o fa'aaogaina e gaosia ai le meafaitino ma le su'ega fa'afefiloi e feso'ota'i ma mea e tausisia.
USP Reference standards <11>-
USP Endotoxin RS
USP Paclitaxel RS Kiliki e Va'ai Fa'atulagaga
USP Paclitaxel Related Compound A RS
Cephalomannine.
USP Paclitaxel Related Compound B RS
10-Deacetyl-7-Epipaclitaxel.
USP Paclitaxel Fa'afefiloi Fa'afefiloi RS
Faʻafefiloi o Paclitaxel ma mea faʻapipiʻi nei: propyl analog, cephalomannine, sec-butyl analog, n-butyl analog, benzyl analog, baccatin VI, pentyl analog, ma le 7-epipaclitaxel.
Fa'ailoa-
A: Infrared absorption <197K>.
B: O le taimi fa'atumauina o le tumutumu tele i le chromatogram o le sauniuniga Su'esu'e e fetaui ma lena i le chromatogram o le sauniuniga Tulaga, e pei ona maua i le Su'ega.
Ta'amilosaga fa'apitoa 781S: i le va o le 49.0 ma le 55.0 i le 20, fa'atatau i luga o le fa'avae anhydrous, leai se solvent.
Su'ega fofo: 10 mg i le mL, i le methanol.
Su'ega fa'avasegaga ole microbial <61> ma Su'ega mo meaola ninii fa'apitoa <62>-O le aofa'i ole aofa'i ole microbial e le sili atu ile 100 cfu ile g.E fetaui ma manaʻoga o suʻega mo le leai o Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella ituaiga, ma Escherichia coli.
Bacterial endotoxins 85-E le sili atu i le 0.4 USP Endotoxin Unit i mg o paclitaxel.
Suavai, Metotia Ic <921>: e le sili atu i le 4.0%.
Toega ile mumu <281>: e le sili atu i le 0.2%.
Metala mamafa, Metotia II <231>: 0.002%.
Fa'atasiga Fa'atasi-
su'ega 1 (mo mea e fa'ailogaina e tu'ufua mai puna fa'alenatura)-Afai e fa'amalie le mea lea ma lenei su'ega, o le fa'ailoga e fa'ailoa mai e fetaui ma USP Related compound Su'ega 1.
Diluent-Sauni e pei ona faatonuina i le Suʻega.
Fofo A-Sauni le acetonitrile ua fa'amama ma fa'amama.
Fofo B-Sauni le vai ua fa'amama ma fa'amama.
Vaega fe'avea'i-Fa'aaogā fa'afefiloi fesuisuia'i o Fofo A ma Fofo B e pei ona fa'atonuina mo le faiga o le Chromatographic.Faia ni fetuunaiga pe a talafeagai (tagai System Suitability i lalo ole Chromatography 621).
Fofo talafeagai o faiga-Fa'amuta sa'o le mamafa o le USP Paclitaxel Related Compound A RS ma le USP Paclitaxel Related Compound B RS i le methanol e maua ai se vaifofo e iloa fa'amautu e tusa ma le 10 µg o ta'itasi i le mL.Fa'aliliu le 5.0 mL o lenei vaifofo i se fagu volumetric 50-mL, fa'afefiloi ma le Diluent i le voluma, ma fa'afefiloi.
Fofo masani-Fa'amuta, faatasi ai ma le fesoasoani o le sonication, se aofaiga sa'o le fuaina o le USP Paclitaxel RS i le Diluent, ma dilute quantitatively, ma stepwise pe a manaʻomia, ma le Diluent e maua ai se vaifofo o loʻo i ai se faʻatonuga iloa e uiga i le 5 µg i le mL.
Su'ega fofo-Fa'aoga le sauniuniga Su'ega.
Chromatographic system (silasila Chromatography <621>)-O le chromatograph vai ua fa'apipi'iina i se fa'amatalaga 227-nm ma se koluma 4.6-mm × 25-cm o lo'o iai le 5-µm fa'apipi'i L43.Ole fua ole tafe e tusa ma le 2.6 mL ile minute.O le vevela o le koluma e faʻatumauina i le 30. O le chromatograph ua faʻapipiʻiina e pei ona taua i lalo.
Taimi (minute) Fofo A (%) Fofo B (%) Elution
0–35 35 65 fa'aisocratic
35–60 35®80 65®20 gradient laina
60–70 80®35 20®65 gradient laina
70–80 35 65 isocraticChromatograph le fa'aogaina o le System, ma fa'amaumau tali pito i luga e pei ona fa'atonuina mo le Fa'atinoga: o taimi fa'atumauina e tusa ma le 0.78 mo le paclitaxel feso'ota'iga A ma le 0.86 mo le paclitaxel feso'ota'iga fa'atasi B (fa'atatau i le taimi fa'atumauina mo paclitaxel maua mai. le Su'ega fofo);ma o le iugafono, R, i le va o le paclitaxel related compound A ma le paclitaxel related compound B e le itiiti ifo i le 1.0.Chromatograph le vaifofo Fa'ata'atia, ma fa'amaumau tali pito i luga e pei ona fa'atonuina mo le Fa'atinoga: ole va'aiga fa'atatau mo tui fa'atusa e le sili atu ile 2.0%.
Faiga-Tu'i se voluma (pe tusa ma le 15 µL) o le vaifofo o le Su'ega i totonu o le chromatograph, faamaumau le chromatogram, ma fua vaega mo tumutumu tetele.Fa'atatau le pasene o mea leaga ta'itasi ile vaega ole Paclitaxel e ave ile fua fa'atatau:
100(Ai/RU)
lea o le F o le fa'atatau tali tali mo pito i'a ta'itasi (silasila i le Laulau 1 mo tau);ri o le vaega pito i luga o le eleelea taitasi;ma le rU o le pito maualuga lea mo paclitaxel.
Laulau 1
Taimi Taofi Fa'atatau Fa'atatau Tali Tali (F) Fa'agata Igoa (%)
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 related compound A) a11
0.78 1.26 2'',3''-Dihydrocephalomannine a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel feso'ota'i fa'atasi 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 Atonu e le atoatoa le fa'ai'uga mo nei tumutumuga, e fa'atatau ile aofa'iga o lo'o iai;o le aofaiga o le a1 ma le a2 e le sili atu i le 0.5%.
2 Atonu e le atoatoa le fa'ai'uga mo nei tumutumuga, e fa'atatau i le aofa'i o lo'o iai;ole aofaiga ole b1 ma le b2 e le sili atu i le 0.5%.
3 O le igoa kemikolo o lo'o taua i lalo o lo'o tu'uina atu i le mea fa'aopoopo, benzyl analog:Baccatin III 13-ester ma le (2R,3S)-2-hydroxy-3-phenyl-3-(2-phenylacetylamino)propanoic acid.
E le gata i le le sili atu i tapula'a mo paclitaxel e feso'ota'i ma mea leaga i le Laulau 1, e le sili atu i le 0.1% o so'o se isi mea leaga e maua;ma e le sili atu i le 2.0% o le aofaʻi o mea leaga e maua.
su'ega 2 (mo meafaitino ua fa'ailogaina e pei ona gaosia i se faiga semisynthetic)— Afai e fa'amalie le mea i lenei su'ega, o le fa'ailoga e fa'ailoa mai e fetaui ma USP Related compound Su'ega 2.
Diluent-Fa'aoga acetonitrile.
Fofo A-Fa'aaogā se fa'afefiloi ua fa'amama ma fa'amama o le vai ma le acetonitrile (3:2).
Fofo B-Fa'aaoga le acetonitrile ua fa'amama ma fa'amama.
Vaega fe'avea'i-Fa'aaogā fa'afefiloi fesuisuia'i o Fofo A ma Fofo B e pei ona fa'atonuina mo le faiga o le Chromatographic.Faia ni fetuunaiga pe a talafeagai (tagai System Suitability i lalo ole Chromatography 621).
Fofo talafeagai faiga-Fa'amuta sa'o le mamafa o le USP Paclitaxel RS ma le USP Paclitaxel Related Compound B RS i le Diluent, lulu ma sonicating pe a mana'omia, e maua ai se vaifofo e iloa fa'atonuga e tusa ma le 0.96 mg ma le 0.008 mg i le mL, fa'asologa.
Fofo o le su'ega-Fa'asolo pe tusa ma le 10 mg o le Paclitaxel, fuaina sa'o, i se fagu volumetric 10-mL, fa'amuta i totonu ma fa'afefete i le Diluent i le voluma, lulu ma sonic pe a mana'omia, ma fa'afefiloi.
Chromatographic system (silasila Chromatography 621)— O le chromatograph vai o lo'o fa'apipi'iina i le 227-nm detector ma le 4.6-mm × 15-cm koluma e iai le 3-µm fa'apipi'i L1.Ole fua ole tafe e tusa ma le 1.2 mL ile minute.O le vevela o le koluma e faʻatumauina i le 35. O le chromatograph ua faʻapipiʻiina e pei ona taua i lalo.
Taimi (minute) Fofo A (%) Fofo B (%) Elution
0-20 100 0 fa'aisocratic
20-60 100®10 0®90 gradient laina
60-62 10®100 90®0 gradient laina
62-70 100 0 isocraticChromatograph le fa'aogaina o le Faiga, ma fa'amaumau tali pito i luga e pei ona fa'atonuina mo le Fa'atinoga: o taimi fa'atumauina e tusa ma le 0.94 mo le paclitaxel e feso'ota'i fa'atasi B ma le 1.0 mo le paclitaxel;o le iugafono, R, i le va o le paclitaxel e feso'ota'i fa'atasi B ma le paclitaxel e le itiiti ifo i le 1.2;ma o le eseesega o tulaga masani mo tui toe faia e le sili atu i le 2.0%.
Faiga-Tu'i ese voluma tutusa (tusa ma le 15 µL) o le Su'ega ma le Su'ega vaifofo i totonu o le chromatograph, faamaumau le chromatograms, ma fua vaega mo tumutumu uma.Fa'aleaogaina so'o se tumutumu ona o le Diluent.Fa'atatau le pasene o mea leaga ta'itasi ile vaega ole Paclitaxel e ave ile fua fa'atatau:
100(Ai/rs)
o le F o le tali fa'atatau mo mea leaga ta'itasi (silasila i le Laulau 2 mo tau);ri o le vaega pito i luga o le eleelea taitasi e maua mai le vaifofo o le Su'ega;ma le rs o le aofa'iga o vaega o tumutumu uma na maua mai le vaifofo o le Su'ega.
Laulau 2
Taimi Taofi Fa'atatau Fa'atatau Tali Tali (F) Fa'agata Igoa (%)
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 Tatala mama Oxetane, acetyl ma benzoyl ua malaga atu2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel feso'ota'i fa'atasi 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 Atonu e le atoatoa le fa'ai'uga mo nei tumutumuga, e fa'atatau ile aofa'iga o lo'o iai;o le aofaiga o le x1, x2, ma le x3 e le sili atu i le 0.4%.
2 O igoa nei vaila'au ua tu'uina atu i mea fa'apipi'i fa'atatau Photodegradant;Tatala mama Oxetane, acetyl ma benzoyl malaga;ma le 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
Tatala mama Oxetane, acetyl ma benzoyl malaga ese
(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 ma (2R,3S) -2-hydroxy-3-phenyl-3-(phenylcarbonylamino) propanoic acid, 10-ester ma (2S,3S) -2-hydroxy-3-phenyl-3-(phenylcarbonylamino ) acid propanoic
E le gata i le le sili atu i tapula'a mo paclitaxel e feso'ota'i ma mea leaga i le Laulau 2, e le sili atu i le 0.1% o so'o se isi mea leaga e maua;ma e le sili atu i le 2.0% o le aofaʻi o mea leaga e maua.
su'ega 3 (mo meafaitino ua fa'ailogaina e pei ona gaosia e se faiga fa'afefeteina sela o la'au)— Afai e fa'amalie le mea lea ma lenei su'ega, o le fa'ailoga e fa'ailoa ai e fetaui ma le USP Related compound Test 3.
Fofo A-Sauni se paluga ua fa'amama ma fa'amama o le vai ma le acetonitrile (3:2).
Fofo B-Sauni le acetonitrile ua fa'amama ma fa'amama.
Vaega fe'avea'i-Fa'aaogā fa'afefiloi fesuisuia'i o Fofo A ma Fofo B e pei ona fa'atonuina mo le faiga o le Chromatographic.Faia ni fetuunaiga pe a talafeagai (tagai System Suitability i lalo ole Chromatography 621).
Fofo talafeagai faiga-Fa'amuta USP Paclitaxel Fa'afefiloi Fa'afefiloi RS i acetonitrile, sonicating pe a mana'omia, e maua ai se vaifofo o lo'o i ai se fa'atonuga iloa e tusa ma le 1 mg i le mL.
Fofo masani-Fa'amuta se aofa'i sa'o le fuaina o le USP Paclitaxel RS i le acetonitrile, sonicating pe a mana'omia, e maua ai se vaifofo o lo'o i ai se fa'atonuga iloa e tusa ma le 1 mg i le mL.
Fofo o le su'ega-Fa'aliliu pe tusa ma le 10 mg o le Paclitaxel, fa'atatau sa'o, i se fagu volumetric 10-mL.Fa'amuta i totonu ma fa'afefiloi i le acetonitrile i le voluma, sonicating pe a mana'omia, ma fa'afefiloi.
Chromatographic system (silasila Chromatography 621)— O le chromatograph vai o lo'o fa'apipi'iina i le 227-nm detector ma le 4.6-mm × 15-cm koluma e iai le 3-µm fa'apipi'i L1.Ole fua ole tafe e tusa ma le 1.2 mL ile minute.Ua fa'apolokalameina le chromatograph e fa'apea.
Taimi (minute) Fofo A (%) Fofo B (%) Elution
0-28 100 0 fa'aisocratic
28-33 100®98 0®2 gradient laina
33–58 98®10 2®90 gradient laina
58-60 10 90 faaitu'au
60-63 10®100 90®0 gradient laina
63-70 100 0 isocraticChromatograph le vaifofo talafeagai Faiga, ma faamaumau tali pito i luga e pei ona faatonuina mo Faiga: o le iugafono, R, i le va o le paclitaxel ma le benzyl analog e le itiiti ifo i le 1.8.Chromatograph le vaifofo Fa'ata'atia, ma fa'amaumau tali pito i luga e pei ona fa'atonuina mo le Fa'atinoga: ole va'aiga fa'atatau mo tui fa'atusa e le sili atu ile 2.0%.[fa'amatalaga—Mo le fa'amoemoega o le fa'ailoaina o tumutumu, o taimi fa'atumauina fa'atatau o lo'o tu'uina atu i le Siata 3. O taimi fa'amautu fa'atatau o lo'o fua ma Paclitaxel.]
Laulau 3
Igoa Fa'agata Taimi Taofi (%)
Propyl analog1 0.54 0.2
Cephalomannine (Paclitaxel feso'ota'i fa'atasi 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
Pentil analog4 1.31 0.2
7-Epipaclitaxel 1.51 0.4
1 O le igoa vaila'au o lo'o taua i lalo o lo'o tu'uina atu i le fa'aoga tutusa Propyl analog:Baccatin III 13-ester ma (2R,3S) -3-bunoylamino-2-hydroxy-3-phenylpropanoic acid.
2 O le igoa vailaʻau o loʻo taua i lalo o loʻo tuʻuina atu i le faʻaogaina sec-Butyl analog:Baccatin III 13-ester ma (2R,3S) -2-hydroxy-3-(2-methylbunoylamino) -3-phenylpropanoic acid.
3 O le igoa vaila'au o lo'o taua i lalo o lo'o tu'uina atu i le fa'aogaina o le n-Butyl analog:Baccatin III 13-ester ma le (2S,3S) -2-hydroxy-3-(pentanoylamino) -3-phenylpropanoic acid.
4 O le igoa vaila'au o lo'o taua i lalo o lo'o tu'uina atu i le fa'aogaina o le Pentyl analog:Baccatin III 13-ester fa'atasi ma le (2R,3S)-3-(hexanoylamino)-2-hydroxy-3-phenylpropanoic acid.
Faiga-Tu'i se voluma (pe tusa ma le 12 µL) o le vaifofo o le Su'ega i totonu o le chromatograph, faamaumau le chromatogram, ma fua vaega mo tumutumu uma.Fa'atatau le pasene o mea leaga ta'itasi ile vaega ole Paclitaxel e ave ile fua fa'atatau:
100(ri/rU)
lea e i ai ri le tali a tagata ta'ito'atasi le mama;ma le rU o le aofaiga o vaega o tumutumu uma e maua mai le vaifofo o le Su'ega.E le gata i le le sili atu i tapula'a mo paclitaxel e feso'ota'i ma mea leaga o lo'o i le Laulau 3, e le sili atu i le 0.1% o so'o se isi mea leaga e maua;ma e le sili atu i le 2.0% o le aofaʻi o mea leaga e maua.
Su'ega-
Diluent-Sauni se paluga ole methanol ma le acetic acid (200:1).
Vaega fe'avea'i-Sauni se paluga ua fa'amama ma fa'amama o le vai ma le acetonitrile (11:9).Faia ni fetuunaiga pe a talafeagai (tagai System Suitability i lalo ole Chromatography 621).
Tulaga masani-Fa'amama, fa'aaoga sonication pe a mana'omia, se fua sa'o fua o le USP Paclitaxel RS i le Diluent, ma fa'amalulu quantitatively, ma stepwise pe a mana'omia, ma le Diluent e maua ai se vaifofo o lo'o i ai se fa'atonuga iloa e uiga i le 1 mg i le mL.
Sauniuniga su'esu'e- Fa'aliliu pe tusa ma le 10 mg o le Paclitaxel, fa'asa'o le mamafa, i se fagu volumetric 10-mL.Fa'amuta ile Diluent, fa'aaoga le sonication pe a mana'omia, fa'afefiloi ma le Diluent i le voluma, ma fa'afefiloi.
Chromatographic system (silasila Chromatography <621>)-O le chromatograph vai ua fa'apipi'iina i se fa'amatalaga 227-nm ma se koluma 4.6-mm × 25-cm o lo'o iai le 5-µm fa'apipi'i L43.Ole fua ole tafe e tusa ma le 1.5 mL ile minute.Chromatograph le Sauniuniga Fa'ata'atia, ma fa'amaumau tali pito i luga e pei ona fa'atonuina mo le Fa'atinoga: o le fa'asologa o le si'usi'u i le va o le 0.7 ma le 1.3;ma o le eseesega tulaga masani mo tui toe faia e le sili atu i le 1.5%.
Faiga-Tu'i ese voluma tutusa (tusa ma le 10 µL) o le sauniuniga Fa'ata'atia ma le Su'ega Su'ega i totonu o le chromatograph, fa'amaumau le chromatograms, ma fua vaega mo tumutumu tetele.Fa'atatau le aofa'i, i mg, o le C47H51NO14 i le vaega o le Paclitaxel na fa'aaogaina e le fua fa'atatau:
10C(rU / rS)
o le C o le faʻatonuga, i mg i le mL, o le USP Paclitaxel RS i le sauniuniga Tulaga;ma le rU ma le rS o tali pito i luga mo paclitaxel na maua mai le Su'ega Su'ega ma le Tulaga Fa'atonu.