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-hal 6, 12b-diacetate, 12-benzoate, 9-ester leh (2R,3S) -N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel wuxuu ka kooban yahay wax aan ka yarayn 97.0 boqolkiiba oo aan ka badnayn 102.0 boqolkiiba C47H51NO14, oo lagu xisaabiyo ku salaysan aan dareeraha lahayn.
[Caution-Paclitaxel waa cytotoxic.Waa in si weyn loo taxaddaraa si looga hortago in la neefsado walxaha Paclitaxel iyo in maqaarka loo bandhigo.]
Baakadaha iyo kaydinta-Ku xafid weelasha cidhiidhiga ah, iftiinka u adkaysta, oo ku kaydi heerkulka qolka kontaroolan.
Calaamadeynta-Calaamadeynta waxay muujineysaa nooca habka loo isticmaalo si loo soo saaro walxaha iyo tijaabinta isku dhafka laxiriira ee walxaha u hoggaansamaan.
Heerarka Tixraaca USP <11>-
USP Endotoxin RS
USP Paclitaxel RS Guji si aad u aragto Qaabdhismeedka
Isku dhafka USP Paclitaxel La Xiriira A RS
Cephalomannine.
Isku dhafka USP Paclitaxel La Xiriira B RS
10-Deacetyl-7-Epipaclitaxel.
Isku dhafka wasakhaysan ee USP Paclitaxel RS
Isku dhafka Paclitaxel iyo xeryahooda la xiriira: propyl analog, cephalomannine, sec-butyl analogue, n-butyl analog, benzyl analog, baccatin VI, pentyl analooga, iyo 7-epipaclitaxel.
Aqoonsiga -
J: Nuugista Infrared <197K>.
B: Waqtiga haynta ee ugu sarreysa chromatogram-ka diyaarinta Assay waxay u dhigantaa tan ku jirta chromatogram-ka diyaarinta Heerka, sida laga helay Assay.
Wareeg gaar ah 781S: inta u dhaxaysa 49.0 iyo 55.0 at 20, lagu xisaabiyaa ku salaysan anhydrous, dareere-free.
Xalka tijaabada: 10 mg halkii ml, methanol.
Tijaabada tirinta microbial <61> iyo Tijaabooyin lagu eegayo nooleyaal cayiman <62>- Wadarta tirada microbial aerobic kama badna 100 cfu gkiiba.Waxay buuxisaa shuruudaha imtixaannada maqnaanshaha Staphylococcus aureus, Pseudomonas aeruginosa, noocyada Salmonella, iyo Escherichia coli.
Bakteeriyada endotoxins 85-Waxay ka kooban tahay wax aan ka badnayn 0.4 USP Endotoxin Unit halkii mg ee paclitaxel.
Biyaha, Habka Ic <921>: aan ka badnayn 4.0%.
Hadhaaga dabka <281>: aan ka badnayn 0.2%.
Biraha culus, Habka II <231>: 0.002%.
Isku dhafka la xiriira-
Tijaabada 1 (walaxda lagu calaamadeeyay sida ka go'doonsan ilaha dabiiciga ah) -Haddii walxuhu u hoggaansamo tijaabadan, calaamadaynta waxay muujinaysaa inay la kulmeyso iskudhisyada USP ee la xidhiidha Tijaabada 1.
Diluent-U diyaari sida lagu faray Imtixaanka.
Xalka A- Diyaari acetonitrile la sifeeyay oo soo degsaday.
Xalka B- Diyaari biyo la sifeeyay oo la shiday.
Marxaladda mobilada-Isticmaal isku dhafka kala duwan ee Xalka A iyo Xalka B sida lagu faray nidaamka Chromatographic.Samee hagaajin haddii loo baahdo (eeg Habboonaanta Nidaamka ee hoos timaada Chromatography 621).
Xalka ku habboonaanta nidaamka-U milmi tirada saxda ah ee la miisaamay ee USP Paclitaxel La xidhiidha Isku-xidhka A RS iyo USP Paclitaxel La xidhiidha Isku-xidhka B RS ee methanol si loo helo xal la og yahay oo ku saabsan 10 µg midkiiba mL.Ku wareeji 5.0 mL ee xalkan ilaa 50-mL weel mug leh, ku milmi Diluent ilaa mugga, oo qas.
Xalka caadiga ah-Milan, iyadoo la kaashanayo sonication, tiro si sax ah loo miisaamay ee USP Paclitaxel RS in Diluent, iyo milo tiro, iyo tallaabo haddii loo baahdo, la Diluent si aad u hesho xal isagoo diirada la og yahay oo ku saabsan 5 µg halkii ml.
Tijaabi xalka-Isticmaal diyaarinta Assay.
Nadaamka Chromatographic (eeg Chromatography <621>)-Kromaatograph-ka dareeraha ah waxa uu ku qalabaysan yahay 227-nm baaraha iyo tiir 4.6-mm × 25-cm ah oo ka kooban 5-µm xirmo L43.Heerka socodka waa qiyaastii 2.6 mL daqiiqadii.Heerkulka tiirka waxaa lagu hayaa 30. chromatograph-ka waxaa loo habeeyey sida soo socota.
Waqtiga (daqiiqado) Xalka A (%) Xalka B (%) Elution
0-35 35 65 cibaadaysi
35–60 35®80 65®20 jaanis toosan
60–70 80®35 20®65 jaanis toosan
70-80 35 65 isocraticChromatograph xalka ku habboonaanta nidaamka, oo qor jawaabaha ugu sarreeya sida lagu faray Habraaca: waqtiyada haynta qaraabo waxay ku saabsan yihiin 0.78 ee xarunta la xidhiidha paclitaxel A iyo 0.86 ee xarunta la xidhiidha paclitaxel B (marka loo eego wakhtiga haynta ee paclitaxel laga helay Xalka Imtixaanka);iyo xallinta, R, inta u dhaxaysa xayndaabka laxiriira paclitaxel A iyo paclitaxel ee laxiriira xayndaabka B kama yara 1.0.Chromatograph the Standard Xalka, oo qor jawaabaha ugu sarreeya sida lagu faray Habka: jaangooyada heerka qaraabo ee cirbadaha soo noqnoqda kama badna 2.0%.
Habka-Ku dur mugga (qiyaastii 15 µL) ee xalka Tijaabada chromatograph-ka, duub chromatogramka, oo cabbir meelaha ugu sarreeya.Xisaabi boqolkiiba wasakh kasta ee qaybta Paclitaxel ee ay qaadatay qaacidada:
100 (Jimce / rU)
taas oo F ay tahay qodobka jawaabta u dhiganta ee ugu sarraysa wasakh kasta (eeg shaxda 1 ee qiyamka);ri waa meesha ugu sarreysa ee nijaasta shaqsi kasta;iyo RU waa meesha ugu sarreysa ee paclitaxel.
Shaxda 1
Wakhtiga Haynta Qaraabada Sababta Jawaabta Qaraabo (F) Xadka Magaca (%)
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 xiriir la leh A) a11
0.78 1.26 2'',3''-Dihydrocephalomanninine a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (wax laxiriira Paclitaxel B) 0.5
1.10 1.00 Benzyl analooga3 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 Waxa laga yaabaa in xalku aanu u dhamaystirnayn meelahan ugu sarreeya, iyadoo ku xidhan qadarka qaraabada ah ee jooga;wadarta a1 iyo a2 kama badna 0.5%.
2 Waxa laga yaabaa in xalku u dhamaystirmi waayo meelaha ugu sarreeya, iyadoo ku xidhan qaddarka qaraabada ah ee jooga;wadarta b1 iyo b2 kama badna 0.5%.
3 Magacan kiimikaad ee soo socda ayaa loo qoondeeyay isku-xidhka la xidhiidha, analoogga benzyl:Baccatin III 13-ester oo leh (2R,3S) -2-hydroxy-3-phenyl-3-(2-phenylacetylamino)propanoic acid.
Marka lagu daro in aan ka badnayn xadka wasakhda la xidhiidha paclitaxel ee Shaxda 1, in aan ka badnayn 0.1% wax kasta oo wasakh kale ah ayaa la helaa;oo aan ka badnayn 2.0% wadarta wasakhda la helay.
Tijaabada 2 (walaxda loo calaamadeeyay sida ay soo saartay hab-socod semisynthetic) - Haddii walxuhu u hoggaansamo tijaabadan, calaamadaynta waxay muujinaysaa inay la kulanto isku xidhka USP ee la xidhiidha Tijaabada 2.
Qalab-Isticmaal acetonitrile.
Xalka A-Isticmaal isku dhafka biyaha iyo acetonitrile la sifeeyay oo soo degsaday (3:2).
Xalka B-Isticmaal acetonitrile la sifeeyay oo soo degsaday.
Marxaladda mobilada-Isticmaal isku dhafka kala duwan ee Xalka A iyo Xalka B sida lagu faray nidaamka Chromatographic.Samee hagaajin haddii loo baahdo (eeg Habboonaanta Nidaamka ee hoos timaada Chromatography 621).
Xalka ku habboonaanta nidaamka-Milan si sax ah oo loo miisaamay tirada USP Paclitaxel RS iyo USP Paclitaxel Related Compound B RS in Diluent, ruxitaanka iyo sonicating haddii loo baahdo, si loo helo xal isagoo la og yahay uruursan oo ku saabsan 0.96 mg iyo 0.008 mg per mL, siday u kala horreeyaan.
Tijaabada xalka-Ku wareeji qiyaastii 10 mg ee Paclitaxel, oo si sax ah loo miisaamay, ilaa 10-mL weel mug leh, ku milmi oo ku milmi Diluent ilaa mugga, ruxidda iyo sonicating haddii loo baahdo, isku dar.
Nadaamka Chromatographic (eeg Chromatography 621)—Kromaatograph-ka dareeraha ah waxa uu ku qalabaysan yahay 227-nm baaraha iyo tiir 4.6-mm × 15-cm ah oo ka kooban 3-µm xirmo L1.Heerka socodka waa qiyaastii 1.2 mL daqiiqadii.Heerkulka tiirka waxaa lagu hayaa 35. chromatograph-ka waxaa loo habeeyey sida soo socota.
Waqtiga (daqiiqado) Xalka A (%) Xalka B (%) Elution
0-20 100 0 isocratic
20-60 100®10 0®90 jaanis toosan
60-62 10®100 90®0 jaanis toosan
62-70 100 0 isocraticChromatograph ee habka ku habboonaanta nidaamka, oo qor jawaabaha ugu sarreeya sida lagu faray habraaca: waqtiyada haynta qaraabo waxay ku saabsan yihiin 0.94 ee xarunta paclitaxel ee la xidhiidha B iyo 1.0 ee paclitaxel;xallinta, R, inta u dhaxaysa paclitaxel ee la xidhiidha isku dhafka B iyo paclitaxel waa mid aan ka yarayn 1.2;iyo weecasho heerka qaraabo ah ee cirbadaha soo noqnoqda kama badna 2.0%.
Habka-Si gooni ah u duri mugga siman (qiyaastii 15 µL) ee dareeraha iyo xalka tijaabada chromatograph-ka, duub chromatogram-yada, oo cabbir aagagga dhammaan meelaha ugu sarreeya.Iska ilaali wax kasta oo ugu sarreeya sababtoo ah dareeraha.Xisaabi boqolkiiba wasakh kasta ee qaybta Paclitaxel ee ay qaadatay qaacidada:
100 (Jimcaha / s)
taas oo F ay tahay qodobka jawaabta u dhigma ee wasakh kasta (eeg shaxda 2 ee qiimayaasha);ri waa meesha ugu sarreysa ee wasakh kasta oo laga helo xalka Tijaabada;iyo rs waa wadarta aagagga dhammaan meelaha ugu sarreeya ee laga helay xalka Imtixaanka.
Shaxda 2
Wakhtiga Haynta Qaraabada Sababta Jawaabta Qaraabo (F) Xadka Magaca (%)
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 giraanta la furay, acetyl iyo benzoyl guuray2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (wax laxiriira 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 Waxa laga yaabaa in xalku aanu u dhamaystirnayn meelahan ugu sarreeya, iyadoo ku xidhan qadarka qaraabada ah ee jooga;wadarta x1, x2, iyo x3 kama badna 0.4%.
2 Magacyada kiimikaad ee soo socda ayaa loo qoondeeyay isku-dhisyada la xidhiidha Photodegradant;giraanta Oxetane furay, acetyl iyo benzoyl guuray;iyo 10,13-Bissidechainpaclitaxel:
Sawirqaade
(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
giraanta Oxetane waa furmay, acetyl iyo benzoyl waa guureen
(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 leh (2R,3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino) propanoic acid, 10-ester leh (2S,3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino). )propanoic acid
Marka lagu daro in aan ka badnayn xadka wasakhda la xidhiidha paclitaxel ee Shaxda 2, in aan ka badnayn 0.1% wax kasta oo wasakh kale ah ayaa la helaa;oo aan ka badnayn 2.0% wadarta wasakhda la helay.
Tijaabada 3 (walaxda lagu calaamadeeyay sida ay soo saartay habka halsano ee unugga dhirta) - Haddii walxuhu u hoggaansamo tijaabadan, calaamadaynta waxay muujinaysaa inay la kulanto isku xidhka USP ee la xidhiidha Tijaabada 3.
Xalka A- Diyaari isku dhafka biyaha iyo acetonitrile la sifeeyay oo la soo dejiyay (3:2).
Xalka B- Diyaari acetonitrile la sifeeyay oo soo degsaday.
Marxaladda mobilada-Isticmaal isku dhafka kala duwan ee Xalka A iyo Xalka B sida lagu faray nidaamka Chromatographic.Samee hagaajin haddii loo baahdo (eeg Habboonaanta Nidaamka ee hoos timaada Chromatography 621).
Xalka ku habboonaanta nidaamka-Milan USP Paclitaxel Impurity Mixture RS in acetonitrile, sonicating haddii loo baahdo, si loo helo xal isagoo diirada la og yahay oo ku saabsan 1 mg halkii ml.
Xalka caadiga ah-Milan tirada saxda ah ee la miisaamay ee USP Paclitaxel RS in acetonitrile, sonicating haddii loo baahdo, si aad u hesho xal isagoo diirada la og yahay oo ku saabsan 1 mg halkii ml.
Tijaabada xalinta-Ku wareeji qiyaastii 10 mg ee Paclitaxel, si sax ah loo miisaamay, una wareeji caas mug leh oo 10-ml ah.Ku milmi oo ku qas acetonitrile ilaa mugga, sonicating haddii loo baahdo, oo qas.
Nadaamka Chromatographic (eeg Chromatography 621)—Kromaatograph-ka dareeraha ah waxa uu ku qalabaysan yahay 227-nm baaraha iyo tiir 4.6-mm × 15-cm ah oo ka kooban 3-µm xirmo L1.Heerka socodka waa qiyaastii 1.2 mL daqiiqadii.chromatograph-ka waxa loo habeeyey sidan soo socota.
Waqtiga (daqiiqado) Xalka A (%) Xalka B (%) Elution
0-28 100 0 isocratic
28-33 100®98 0®2 jaanis toosan
33–58 98®10 2®90 jaanis toosan
58-60 10 90 isocratic
60-63 10®100 90®0 jaanis toosan
63-70 100 0 isocraticChromatograph ee xalka ku habboonaanta Nidaamka, oo qor jawaabaha ugu sarreeya sida lagu faray Habraaca: xallinta, R, ee u dhexeeya paclitaxel iyo analoogga benzyl kama yarayn 1.8.Chromatograph the Standard Xalka, oo qor jawaabaha ugu sarreeya sida lagu faray Habka: jaangooyada heerka qaraabo ee cirbadaha soo noqnoqda kama badna 2.0%.[Xusuusin-Ujeedada aqoonsiga ugu sarreysa, qiyaastii wakhtiyada haynta qaraabada ayaa lagu bixiyaa shaxda 3. Wakhtiyada haynta qaraabo waxaa lagu qiyaasaa Paclitaxel.]
Shaxda 3
Magaca Xadka Wakhtiga Haynta Qaraabo (%)
Analoogga propyl1 0.54 0.2
Cephalomannine (Paclitaxel xiriir la leh A) 0.76 0.5
sek-Butyl analooga2 0.81 0.2
n-Butyl analooga3 0.89 0.1
Analoogga Benzyl 1.10 0.4
Baccatin VI 1.23 0.2
Analoogga Pentyl 1.31 0.2
7-Epipaclitaxel 1.51 0.4
1 Magacan kiimikaad ee soo socda ayaa loo qoondeeyay isku dhafka la xidhiidha Propyl analoogga:Baccatin III 13-ester oo leh (2R,3S) -3-butanoylamino-2-hydroxy-3-phenylpropanoic acid.
2 Magacan kiimikaad ee soo socda ayaa loo qoondeeyay isku dhafka laxiriira sec-Butyl analoogga:Baccatin III 13-ester oo leh (2R,3S) -2-hydroxy-3- (2-methylbutanoylamino) -3-phenylpropanoic acid.
3 Magacan kiimikaad ee soo socda ayaa loo qoondeeyay isku dhafka n-Butyl analoogga:Baccatin III 13-ester leh (2S,3S) -2-hydroxy-3-(pentanoylamino) -3-phenylpropanoic acid.
4 Magacan kiimikaad ee soo socda ayaa loo qoondeeyay isku dhafka Pentyl analoogga ah:Baccatin III 13-ester oo leh (2R,3S)-3-(hexanoylamino) -2-hydroxy-3-phenylpropanoic acid.
Habka-Ku dur mugga (qiyaastii 12 µL) ee xalka tijaabada chromatograph-ka, duub chromatogramka, oo cabbir aagagga dhammaan meelaha ugu sarreeya.Xisaabi boqolkiiba wasakh kasta ee qaybta Paclitaxel ee ay qaadatay qaacidada:
100 (ri / rU)
taas oo ri ah jawaabta qof kasta oo wasakh ah;iyo rU waa wadarta aagagga dhammaan meelaha ugu sarreeya ee laga helay xalka Imtixaanka.Marka lagu daro in aan ka badnayn xadka wasakhda la xidhiidha paclitaxel ee Shaxda 3, in aan ka badnayn 0.1% wax kasta oo wasakh kale ah ayaa la helaa;oo aan ka badnayn 2.0% wadarta wasakhda la helay.
Imtixaan-
Diluent- Diyaari isku dhafka methanol iyo acetic acid (200:1).
Marxaladda guurguura- Diyaari isku dhafka biyaha iyo acetonitrile la sifeeyay oo la soo dejiyay (11:9).Samee hagaajin haddii loo baahdo (eeg Habboonaanta Nidaamka ee hoos timaada Chromatography 621).
Diyaarinta Standard-Mila, iyadoo la isticmaalayo sonication haddii loo baahdo, tiro si sax ah loo miisaamay ee USP Paclitaxel RS in Diluent, iyo milo tiro, iyo stepwise haddii loo baahdo, la diluent si aad u hesho xal isagoo fiirsashada la og yahay oo ku saabsan 1 mg per mL.
Diyaarinta Assay-Ku wareeji qiyaastii 10 mg oo Paclitaxel ah, oo si sax ah loo miisaamay, una wareejiso 10-mL oo mug leh.Ku milmi diluent, adoo isticmaalaya sonication haddii loo baahdo, ku milmi dareeraha ilaa mugga, oo qas.
Nadaamka Chromatographic (eeg Chromatography <621>)-Kromaatograph-ka dareeraha ah waxa uu ku qalabaysan yahay 227-nm baaraha iyo tiir 4.6-mm × 25-cm ah oo ka kooban 5-µm xirmo L43.Heerka socodka waa qiyaastii 1.5 mL daqiiqadii.Chromatograph ee heerka diyaarinta, oo qor jawaabaha ugu sarreeya sida lagu faray Habka: qodobka dabada ayaa u dhexeeya 0.7 iyo 1.3;iyo leexashada heerka qaraabo ee cirbadaha soo noqnoqda kama badna 1.5%.
Habka-Si gooni ah u duri mugga siman (qiyaastii 10 µL) ee diyaarinta Heerka iyo diyaarinta Assay chromatograph-ka, duub chromatogram-yada, oo cabbir aagagga meelaha ugu sarreeya.Xisaabi tirada, mg, ee C47H51NO14 ee qaybta Paclitaxel ee ay qaadatay qaacidada:
10C (rU / rS)
taas oo C ay tahay xoojinta, mg per mL, ee USP Paclitaxel RS ee diyaarinta Standard;iyo rU iyo rS waa jawaabaha ugu sarreeya ee paclitaxel ee laga helay diyaarinta Assay iyo diyaarinta Heerka, siday u kala horreeyaan.