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-imodzi 6, 12b-diacetate, 12-benzoate, 9-ester ndi (2R,3S)-N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel ili ndi osachepera 97.0 peresenti komanso osapitirira 102.0 peresenti ya C47H51NO14, yowerengedwa pa maziko a anhydrous, opanda zosungunulira.
[Chenjezo-Paclitaxel ndi cytotoxic.Kusamala kwambiri kuyenera kuchitidwa kuti mupewe kutulutsa tinthu ta Paclitaxel ndikuwonetsa khungu.]
Kupaka ndi kusungirako-Sungani zotengera zolimba, zosagwira kuwala, ndikusunga kutentha komwe kumayendetsedwa.
Kulemba-Kulembako kumawonetsa mtundu wa njira yomwe imagwiritsidwa ntchito popanga zinthuzo komanso mayeso okhudzana ndi zinthu zomwe zimagwirizana.
Miyezo yolozera ya USP <11>-
USP Endotoxin RS
USP Paclitaxel RS Dinani kuti muwone Kapangidwe
USP Paclitaxel Related Compound A RS
Cephalomannine.
USP Paclitaxel Yogwirizana Compound B RS
10-Deacetyl-7-Epipaclitaxel.
USP Paclitaxel Impurity Mixture RS
Kusakaniza kwa Paclitaxel ndi mankhwala okhudzana ndi zotsatirazi: propyl analog, cephalomannine, sec-butyl analog, n-butyl analog, benzyl analog, baccatin VI, analog ya pentyl, ndi 7-epipaclitaxel.
Chizindikiritso-
A: Infrared mayamwidwe <197K>.
B: Nthawi yosungira pachimake chachikulu mu chromatogram ya Kukonzekera kwa Assay ikufanana ndi yomwe ili mu chromatogram ya Kukonzekera kwa Standard, monga momwe zapezedwa mu Assay.
Kuzungulira kwachindunji 781S: pakati pa 49.0 ndi 55.0 pa 20, kuwerengedwa pa maziko a anhydrous, opanda zosungunulira.
Njira yothetsera mayeso: 10 mg pa mL, mu methanol.
Mayeso owerengera ma Microbial <61> ndi Mayeso a tinthu tating'onoting'ono <62> -Kuwerengera kwathunthu kwa aerobic microbial sikudutsa 100 cfu pa g.Imakwaniritsa zofunikira pakuyezetsa kusowa kwa Staphylococcus aureus, Pseudomonas aeruginosa, mitundu ya Salmonella, ndi Escherichia coli.
Bakiteriya endotoxins 85-Ilibe kupitirira 0.4 USP Endotoxin Unit pa mg wa paclitaxel.
Madzi, Njira Ic <921>: osapitirira 4.0%.
Zotsalira pakuyatsa <281>: osapitirira 0.2%.
Zitsulo zolemera, Njira II <231>: 0.002%.
Zogwirizana nazo-
kuyesa 1 (kwa zinthu zolembedwa kuti ndizosiyana ndi zachilengedwe) -Ngati zinthuzo zikugwirizana ndi mayesowa, zolembazo zikuwonetsa kuti zikukumana ndi Mayeso 1 a USP Related compounds.
Diluent-Konzekerani monga momwe mwanenera mu Assay.
Yankho A-Konzekerani acetonitrile osefedwa ndi degassed.
Yankho B-Konzani madzi osefedwa ndi opanda mpweya.
Mobile phase-Gwiritsani ntchito zosakanikirana zosakanikirana za Solution A ndi Solution B monga momwe zalembedwera pa Chromatographic system.Sinthani ngati kuli kofunikira (onani Kukwanira Kwadongosolo pa Chromatography 621).
Sungunulani yoyezera bwino kuchuluka kwa USP Paclitaxel Related Compound A RS ndi USP Paclitaxel Related Compound B RS mu methanol kuti mupeze yankho lodziwika bwino la pafupifupi 10 µg pa ml iliyonse.Tumizani 5.0 ml ya yankho ili ku botolo la volumetric 50-mL, tsitsani ndi Diluent mpaka voliyumu, ndikusakaniza.
Standard njira Sungunulani, mothandizidwa ndi sonication, molondola kulemera kuchuluka kwa USP Paclitaxel RS mu Diluent, ndi kuchepetsa quantitatively, ndi stepwise ngati n'koyenera, ndi Diluent kupeza yankho kukhala ndi kudziwika ndende pafupifupi 5 µg pa mililita.
Njira yothetsera-Gwiritsani ntchito kukonzekera kwa Assay.
Chromatographic system (onani Chromatography <621>) - Chromatograph yamadzimadzi imakhala ndi chowunikira cha 227-nm ndi ndime ya 4.6-mm × 25-cm yomwe ili ndi 5-µm yonyamula L43.Kuthamanga kwa madzi ndi pafupifupi 2.6 ml pa mphindi.Kutentha kwapakati kumasungidwa pa 30. Chromatograph imakonzedwa motere.
Nthawi (mphindi) Yankho A (%) Yankho B (%) Kuwunika
0–35 35 65 isokerasi
35–60 35®80 65®20 mzere wopendekera
60–70 80®35 20®65 mzere wopendekera
70–80 35 65 isocraticChromatograph the System kuyenerera yankho, ndi kulemba mayankho pachimake monga momwe anayankhira Ndondomeko: nthawi kusunga wachibale ndi pafupifupi 0.78 kwa paclitaxel zokhudzana pawiri A ndi 0.86 kwa paclitaxel zokhudzana pawiri B (zogwirizana ndi nthawi yosungira paclitaxel yotengedwa kuchokera yankho la Test);ndi kusamvana, R, pakati pa paclitaxel yokhudzana ndi paclitaxel A ndi paclitaxel yokhudzana ndi gulu B ndi yosachepera 1.0.Chromatograph the Standard solution, ndikujambulitsa mayankho apamwamba monga momwe adayankhidwira kachitidwe: kupotokola kofanana kwa jakisoni wobwereza sikudutsa 2.0%.
Kachitidwe-Bayikirani voliyumu (pafupifupi 15 µL) ya njira Yoyesera mu chromatograph, lembani chromatogram, ndikuyesa madera a nsonga zazikulu.Werengani kuchuluka kwa zodetsa zilizonse pagawo la Paclitaxel lotengedwa ndi formula:
100 (Lachisanu / rU)
momwe F ndiye gawo loyankhira pachimake chilichonse chodetsedwa (onani Table 1 pazikhalidwe);ri ndilo nsonga ya malo a chidetso cha munthu aliyense;ndipo rU ndiye malo okwera kwambiri a paclitaxel.
Table 1
Nthawi Yosungika Yachibale Factor 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 related compound A) a11
0.78 1.26 2'',3''-Dihydrocephalomanine a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel yogwirizana ndi B) 0.5
1.10 1.00 Benzyl analogi3 b12
1.10 1.00 3'',4''-Dehydropaclitaxel C b22
1.40 1.00 7-Epicephalomanine 0.3
1.85 1.00 7-Epipaclitaxel 0.5
Chigamulo cha 1 chikhoza kukhala chosakwanira pa nsongazi, kutengera kuchuluka komwe kulipo;kuchuluka kwa a1 ndi a2 sikudutsa 0.5%.
2 Kusamvana kungakhale kosakwanira pa nsongazi, kutengera kuchuluka kwa ndalama zomwe zilipo;kuchuluka kwa b1 ndi b2 sikuposa 0.5%.
3 Dzina la mankhwala otsatirawa limaperekedwa kumagulu okhudzana, benzyl analogi: Baccatin III 13-ester ndi (2R,3S) -2-hydroxy-3-phenyl-3- (2-phenylacetylamino) propanoic acid.
Kuphatikiza pa kusapyola malire a zonyansa zokhudzana ndi paclitaxel mu Table 1, osapitirira 0.1% ya zonyansa zina zilizonse zomwe zimapezeka;ndipo zosaposa 2.0% ya zonyansa zonse zimapezeka.
test 2 (pazinthu zolembedwa kuti zimapangidwa ndi semisynthetic process)— Ngati zinthuzo zikugwirizana ndi mayesowa, zolembazo zikuwonetsa kuti zikukumana ndi Mayeso 2 a USP Related compounds.
Diluent - Gwiritsani ntchito acetonitrile.
Yankho A-Gwiritsirani ntchito madzi osefedwa ndi osungunuka amadzi ndi acetonitrile (3: 2).
Yankho B-Gwiritsani ntchito acetonitrile yosefedwa komanso yochotsa mpweya.
Mobile phase-Gwiritsani ntchito zosakanikirana zosakanikirana za Solution A ndi Solution B monga momwe zalembedwera pa Chromatographic system.Sinthani ngati kuli kofunikira (onani Kukwanira Kwadongosolo pa Chromatography 621).
Dongosolo kuyenerera njira yothetsera Sungunulani molondola kulemera zedi za USP Paclitaxel RS ndi USP Paclitaxel Related Compound B RS mu Diluent, kugwedeza ndi sonicating ngati n'koyenera, kupeza njira podziwa woipa wa za 0,96 mg ndi 0,008 mg wa pa mililita, motero.
Mayeso njira-Choka za 10 mg wa Paclitaxel, molondola kulemera, kwa 10-mL volumetric botolo, kupasuka ndi kuchepetsa ndi Diluent kuti voliyumu, kugwedeza ndi sonicating ngati n'koyenera, ndi kusakaniza.
Chromatographic system (onani Chromatography 621)— Chromatograph yamadzimadzi imakhala ndi chowunikira cha 227-nm ndi ndime ya 4.6-mm × 15-cm yomwe ili ndi 3-µm yonyamula L1.Kuthamanga kwa madzi ndi pafupifupi 1.2 ml pa mphindi.Kutentha kwapakati kumasungidwa pa 35. Chromatograph imakonzedwa motere.
Nthawi (mphindi) Yankho A (%) Yankho B (%) Kuwunika
0-20 100 0 isocratic
20-60 100®10 0®90 mzere wozungulira
60-62 10®100 90®0 mzere wozungulira
62-70 100 0 isocraticChromatograph njira yothetsera kuyenerera kwa System, ndi kulemba mayankho apamwamba monga momwe adayankhira Ndondomeko: nthawi zosungirako zokhudzana ndi 0.94 za paclitaxel yokhudzana ndi gulu B ndi 1.0 ya paclitaxel;kusamvana, R, pakati pa paclitaxel yokhudzana ndi B ndi paclitaxel sikuchepera 1.2;ndipo kupatuka kofanana kwa jakisoni wobwereza sikudutsa 2.0%.
Kachitidwe-Payokha jekeseni ma voliyumu ofanana (pafupifupi 15 µL) a Diluent ndi Test solution mu chromatograph, lembani ma chromatogram, ndikuyesa madera a nsonga zonse.Pewani nsonga zilizonse chifukwa cha Diluent.Werengani kuchuluka kwa zodetsa zilizonse pagawo la Paclitaxel lotengedwa ndi formula:
100 (Lachisanu / rs)
momwe F ndiye gawo loyankhira pa chodetsa chilichonse (onani Table 2 pazikhalidwe);ri ndi malo okwera pachidebe chilichonse chopezedwa kuchokera ku Mayeso;ndipo rs ndi chiŵerengero cha madera a nsonga zonse zopezedwa kuchokera ku Test solution.
Table 2
Nthawi Yosungika Yachibale Factor 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 mphete ya Oxetane inatsegulidwa, acetyl ndi benzoyl anasamuka2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel yogwirizana ndi 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
Chigamulo cha 1 chikhoza kukhala chosakwanira pa nsongazi, kutengera kuchuluka komwe kulipo;kuchuluka kwa x1, x2, ndi x3 sikuposa 0.4%.
2 Mayina a mankhwala otsatirawa amaperekedwa kwa mankhwala okhudzana ndi Photodegradant;mphete ya Oxetane inatsegulidwa, acetyl ndi benzoyl anasamuka;ndi 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
Mphete ya Oxetane inatsegulidwa, acetyl ndi benzoyl zinasamuka
(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 yokhala ndi (2R,3S) -2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoic acid, 10-ester with (2S,3S) -2-hydroxy-3-phenyl-3-(phenylcarbonylamino) propanoic acid
Kuphatikiza pa kusapyola malire a zonyansa zokhudzana ndi paclitaxel mu Table 2, osapitirira 0.1% ya zonyansa zina zilizonse zomwe zimapezeka;ndipo zosaposa 2.0% ya zonyansa zonse zimapezeka.
mayeso 3 (pazinthu zolembedwa kuti amapangidwa ndi njira yowotchera ma cell a chomera)— Ngati zinthuzo zikugwirizana ndi mayesowa, zolembazo zikuwonetsa kuti zikugwirizana ndi Mayeso 3 a USP Related compounds.
Yankho A-Konzani zosakaniza zosefedwa ndi zowonongeka za madzi ndi acetonitrile (3: 2).
Yankho B-Konzani osefedwa ndi degassed acetonitrile.
Mobile phase-Gwiritsani ntchito zosakanikirana zosakanikirana za Solution A ndi Solution B monga momwe zalembedwera pa Chromatographic system.Sinthani ngati kuli kofunikira (onani Kukwanira Kwadongosolo pa Chromatography 621).
Dongosolo kuyenerera njira yothetsera-Sungani USP Paclitaxel Chidetso Chosakaniza RS mu acetonitrile, sonicating ngati n'koyenera, kupeza njira kukhala ndi kudziwika ndende pafupifupi 1 mg pa ml ya.
Standard njira-Sungani molondola kulemera kuchuluka kwa USP Paclitaxel RS mu acetonitrile, sonicating ngati n'koyenera, kupeza njira kukhala ndi kudziwika ndende pafupifupi 1 mg pa ml ya.
Njira yothetsera mayeso-Kusamutsa pafupifupi 10 mg ya Paclitaxel, yoyezedwa molondola, ku botolo la volumetric 10-mL.Sungunulani ndi kuchepetsa ndi acetonitrile kuti voliyumu, sonicating ngati n'koyenera, ndi kusakaniza.
Chromatographic system (onani Chromatography 621)— Chromatograph yamadzimadzi imakhala ndi chowunikira cha 227-nm ndi ndime ya 4.6-mm × 15-cm yomwe ili ndi 3-µm yonyamula L1.Kuthamanga kwa madzi ndi pafupifupi 1.2 ml pa mphindi.Chromatograph imapangidwa motere.
Nthawi (mphindi) Yankho A (%) Yankho B (%) Kuwunika
0-28 100 0 isocratic
28-33 100®98 0®2 mzere wozungulira
33–58 98®10 2®90 mzere wopendekera
58-60 10 90 isocratic
60-63 10®100 90®0 mzere wozungulira
63-70 100 0 isocraticChromatograph njira yothetsera kuyenerera kwa System, ndi kulemba mayankho apamwamba monga momwe adalangizira Ndondomeko: chigamulo, R, pakati pa paclitaxel ndi analogi ya benzyl sichichepera 1.8.Chromatograph the Standard solution, ndikujambulitsa mayankho apamwamba monga momwe adayankhidwira kachitidwe: kupotokola kofanana kwa jakisoni wobwereza sikudutsa 2.0%.[Zindikirani-Pofuna kuzindikiritsa pachimake, nthawi yoyandikira yosungira yaperekedwa mu Gulu 3. Nthawi zosungirako zimayesedwa ndi Paclitaxel.]
Table 3
Tchulani Malire a Nthawi Yosunga Nthawi (%)
Propyl analogi1 0.54 0.2
Cephalomannine (Paclitaxel yokhudzana ndi gulu A) 0.76 0.5
sec-Butyl analogi2 0.81 0.2
n-Butyl analogi3 0.89 0.1
Benzyl analogi 1.10 0.4
Baccatin VI 1.23 0.2
Pentyl analogi4 1.31 0.2
7-Epipaclitaxel 1.51 0.4
1 Dzina la mankhwala otsatirawa limaperekedwa kwa ogwirizana pawiri Propyl analogi:Baccatin III 13-ester ndi (2R,3S) -3-butanoylamino-2-hydroxy-3-phenylpropanoic asidi.
2 Dzina la mankhwala otsatirawa limaperekedwa kwa ogwirizana pawiri sec-Butyl analogi: Baccatin III 13-ester ndi (2R,3S) -2-hydroxy-3-(2-methylbutanoylamino) -3-phenylpropanoic asidi.
3 Dzina la mankhwala otsatirawa limaperekedwa kwa ogwirizana pawiri n-Butyl analogi: Baccatin III 13-ester ndi (2S,3S) -2-hydroxy-3-(pentanoylamino) -3-phenylpropanoic asidi.
4 Dzina la mankhwala otsatirawa limaperekedwa kwa ogwirizana pawiri Pentyl analogi:Baccatin III 13-ester ndi (2R,3S) -3-(hexanoylamino) -2-hydroxy-3-phenylpropanoic acid.
Kachitidwe-Bayikirani voliyumu (pafupifupi 12 µL) ya njira Yoyesera mu chromatograph, lembani chromatogram, ndikuyesa madera a nsonga zonse.Werengani kuchuluka kwa zodetsa zilizonse pagawo la Paclitaxel lotengedwa ndi formula:
100 (ri / rU)
momwe ri ndi yankho la munthu aliyense wosadetsedwa;ndipo rU ndiye chiŵerengero cha madera a nsonga zonse zopezedwa kuchokera ku Test solution.Kuphatikiza pa kusapyola malire a zonyansa zokhudzana ndi paclitaxel mu Table 3, osapitirira 0.1% ya zonyansa zina zilizonse zomwe zimapezeka;ndipo zosaposa 2.0% ya zonyansa zonse zimapezeka.
Kuyesa-
Diluent-Konzani osakaniza methanol ndi asidi asidi (200:1).
Mobile phase-Konzani madzi osefedwa ndi degassed madzi ndi acetonitrile (11:9).Sinthani ngati kuli kofunikira (onani Kukwanira Kwadongosolo pa Chromatography 621).
Standard kukonzekera-Sungani, ntchito sonication ngati n`koyenera, molondola analemera kuchuluka kwa USP Paclitaxel RS mu Diluent, ndi kuchepetsa quantitatively, ndi stepwise ngati n`koyenera, ndi Diluent kupeza njira kukhala ndi kudziwika ndende ya 1 mg wa pa mililita.
Kukonzekera kuyesa-Kutumiza pafupifupi 10 mg ya Paclitaxel, yoyezedwa molondola, ku botolo la volumetric 10-mL.Sungunulani mu Diluent, ntchito sonication ngati n'koyenera, kuchepetsa ndi Diluent kuti voliyumu, ndi kusakaniza.
Chromatographic system (onani Chromatography <621>) - Chromatograph yamadzimadzi imakhala ndi chowunikira cha 227-nm ndi ndime ya 4.6-mm × 25-cm yomwe ili ndi 5-µm yonyamula L43.Kuthamanga kwa madzi ndi pafupifupi 1.5 ml pa mphindi.Chromatograph the Standard kukonzekera, ndikujambulitsa mayankho apamwamba monga momwe adayankhidwira Njira: chinthu chotsalira chili pakati pa 0.7 ndi 1.3;ndipo kupatuka kofanana kwa jakisoni wobwereza sikudutsa 1.5%.
Kachitidwe-Papatula jekeseni ma voliyumu ofanana (pafupifupi 10 µL) a Kukonzekera Kwanthawi zonse ndi kukonzekera kwa Assay mu chromatograph, lembani ma chromatogram, ndikuyesa madera a nsonga zazikulu.Werengani kuchuluka, mu mg, wa C47H51NO14 mu gawo la Paclitaxel lotengedwa ndi formula:
10C (rU / rS)
momwe C ndi ndende, mu mg pa mL, ya USP Paclitaxel RS mu kukonzekera Standard;ndi rU ndi rS ndiwo mayankho apamwamba a paclitaxel omwe amapezeka kuchokera ku Assay kukonzekera ndi kukonzekera Standard, motsatana.