Paclitaxel (Taxol) CAS 33069-62-4 Assay (HPLC) 97.0~ 102.0%

Paclitaxel
C47H51NO14 853.91
Acidum Benzenepropanoicum, -(benzoylamino)--hydroxy-, 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b -dodecahydro-4,11-dihydroxia-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl niensis [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-hexahydroxia-4a,8,13,13 tetramethyl-7,11 methano-5H-cyclodeca[3,4]-benz[1,2-b] bovis 5-one 6, 12b-diacetate, 12-benzoate, 9-ster cum (2R,3S)-N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel non minus quam 97.0 centesimas continet et non plus quam 102.0 centesimas C47H51NO14, in fundamento anhydroso, libero solvendo, continet.
[Cautio-Paclitaxel cytotoxicum est.Diligenter curandum est, ne particulas Paclitaxel attrahat et cutem ei exponat.]
Packaging ac repono-Conserve in strictis, levibus vasis repugnantibus, et repone in temperatura cella moderata.
Labeling-Labeling indicat genus processus usus ad materiam producendam et compositorum affinium experimentorum quibus materia obtemperat.
USP Reference signa <11>-
USP Endotoxin RS
USP Paclitaxel RS Click to View Structure
USP Paclitaxel Related Compone A RS
Cephalomannine.
USP Paclitaxel Related Compone B RS
10-Deacetyl-7-Epipaclitaxel.
USP Paclitaxel Impuritas Mixtura RS
Paclitaxel mixtura et composita sequentia cognata: propyl analog, cephalomannine, sec-butyl analog, n-butyl analog, benzyl analog, baccatin VI, pentyl analog, et 7-epipaclitaxel.
Identification-
A: Absorptio infrared <197K>.
B: Retentionis tempus maioris culminis in praeparatione chromatogrammi Assay respondet illi in praeparatione chromatogram Standardi, prout habetur in Assay.
Imprimis rotationis 781S: inter 49.0 et 55.0 ad 20, computata in fundamento anhydroso, libero solvendo.
Solutio test: 10 mg per mL, in methanolum.
Enumeratio microbialium probat <61> et probationes microorganismos determinatos <62> - Totus aerobicus microbialis comes 100 cfu per g non excedit.Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella species, et Escherichia coll.
Bacterial endotoxins 85 - Continet non plus quam 0.4 USP Endotoxin Unit per mg paclitaxel.
Aqua, Methodus Ic <921>: non plus 4.0%.
Residere ignitionem <281>: non plus quam 0.2%.
Metalla gravia, Methodus II <231>: 0.002%.
Related Compounds-
test 1 (pro materia intitulata separatim a fontibus naturalibus) -Si materia huic probationi obtemperat, titulus indicat eum convenire USP Compositiones Related Test 1 .
Diluent-Para uti in Assay.
Solutio A-Para percolata et acetonitrila dejecta.
Solutio B-Para percolata et dejecta aqua.
Mobile phase-Usus mixtura variabilis Solutio A et Solutio B ut ad systema chromatographicum ordinatur.Fac si opus sit adaptationes (cf. Systema Suitability sub Chromatographia 621).
Ratio congruentia solutionis-dissolve accurate quantitates USP Paclitaxel Compositos A RS et USP Paclitaxel Compositorum affinium B RS in methanolum ad solutionem obtinendam habentes notas concentrationes singulorum circiter 10 µg per mL.Translatio 5.0 mL solutionis huius ad L-mL lagulam volumetricam, diluto volumine diluto, et commisce.
Solutio-dissolve, adhibito sonicatione, quantitatem USP Paclitaxel RS in Diluent accurate ponderatam, quantita- tive dilutam, gradatim, si opus sit, cum Diluent ad solutionem obtinendam cognitam intentionem circiter 5 µg per mL.
Expertus solutione utere Praeparatione Ingredi.
Systema chromatographicum (vide chromatographia <621>) - chromatographum liquor 227-um detectoris instructum et 4.6-mm × 25-cm columna quae continet 5-µm fasciculum L43.Rate fluxus circiter 2.6 mL per minute est.Columella temperatura conservatur 30. Chromatographum hoc modo programmatum est.
Solutio tempus (minuta) Solutio A (%) Solutio B (%) Elution
0-35 35 65 isocratic
35-60 35®80 65®20 gradiente lineari
60-70 80®35 20®65 gradiente lineari
70-80 35 65 isocraticChromatographus Systema convenientiae solutionis, et refero apicem responsionum ad procedendum ordinatum: retentione relativa tempora sunt circiter 0,78 pro paclitaxel composita A et 0,86 pro paclitaxel relata compositi B (relativi ad retentionem temporis pro paclitaxel impetrato ab. solutionem Test);et resolutio R, inter paclitaxel composita A et paclitaxel cognata composita B, non minus quam 1.0.Chromatographa solutio Vexillifero, et refero apicem responsionum ad procedendum directae: vexillum relativum declinationis pro injectionibus replicatis non plus quam 2.0% est.
Procedure-Inject volumen (circiter 15 µL) solutionis testium in chromatographum, chromatogrammum notare et areas ad cacumina maiora metire.Recipis cujusvis immunditiae in portione Paclitaxel sumpta formula:
100(Fri/rU)
in quo F est relativum responsionis factor pro cuiusque immunditiae apicem (vide Tabula 1 ad valores);ri- ia culmen regio cuique impudicitiae;et rU areae ad apicem paclitaxel.
Table 1
Relative retentione 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 affinis A compositum) a11
0.78 1.26 2'',3''-Dihydrocephalomannine a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel affinis compositi 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 Resolutio potest esse imperfecta pro his iugis, secundum quantitates relativas praesentes;summa a1 et a2 non plus quam 0.5%.
2 Resolutio potest esse imperfecta pro his iugis, secundum quantitates relativas praesentes;summa b1 et b2 non plus quam 0.5%.
3 Sequens nomen chemicum attribuitur compositioni affinis, benzyl analogi: Baccatin III 13-ester cum (2R,3S)-2-hydroxy-3-phenyl-3-(2-phenylacetylamino) acidum propanoicum.
Praeter limites paclitaxel affines immunditias in Tabula 1, non plus quam 0.1% quarumlibet immunditiarum unica reperitur;et non plus quam 2.0% plenarum immunditiarum invenimus.
test 2 (pro materiali intitulato processu semisynthetico producto) — Si materia huic probationi obtemperat, titulus indicat convenire USP Compositiones Related Test 2 .
Diluent-Usum acetonitrile.
Solutio in aqua et acetonitrili percolata et sparsa utere (3:2).
Solutio B-Usus acetonitri percolato et dejecto.
Mobile phase-Usus mixtura variabilis Solutio A et Solutio B ut ad systema chromatographicum ordinatur.Fac si opus sit adaptationes (cf. Systema Suitability sub Chromatographia 621).
Ratio congruentia solutionis-dissolve accurate pondera USP Paclitaxel RS et USP Paclitaxel Compositum B RS in Diluent, commotionem et sonicans, si opus est, solutionem obtinendam habentes concentrationes notarum circiter 0,96 mg et 0.008 mg per mL, respective.
Expertus solutionis-Translatio circa 10 mg de Paclitaxel accurate perpensa, lagena voluminis 10-mL, dissolve et dilue cum diluto ad volumen, si opus est, collisio et sonicans, et misce.
Systema chromatographicum (cf. chromatographia 621) — chromatographum liquor 227-um detectoris instructum et 4.6-mm × 15-cm columna quae continet 3-µm fasciculum L1.Rate fluens fere 1.2 mL per minutum est.Columella temperatura conservatur 35. Chromatographum hoc modo programmata est.
Solutio tempus (minuta) Solutio A (%) Solutio B (%) Elution
0-20 100 0 isocratic
20-60 100®10 0®90 clivus linearis
60-62 10®100 90®0 gradiente lineari
62-70 100 0 isocraticChromatographum Systematis solutionis idoneitatis, et refero apicem responsionum ad procedendum directae: relativa retentione tempora sunt circiter 0.94 pro paclitaxel composita B et 1.0 pro paclitaxel relata;resolutio, R, inter paclitaxel composita B et paclitaxel cognata non minus quam 1.2;et vexillum relativum declinationis ad injectiones replicatas non plus quam 2.0%.
De modo procedendi-Separatim injiciunt aequalia volumina (circa 15 µL) solutionis diluentis et testi in chromatographum, chromatogrammata notare, et areas omnibus iugis metire.Culmina contemnere debita Diluent.Recipis cujusvis immunditiae in portione Paclitaxel sumpta formula:
100(Fri/rs)
in quo F est elementum relativum responsionis pro qualibet immunditia (vide Tabula 2 ad valores);ri* eft culmen regio pro cujusvis immunditiae ex teftium solutione impe- ;et rs est summa arearum omnium iugis ex solutione Test.
Table 2
Relative retentione 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
0.47 1.00 10-Deacetylpaclitaxel 0.5
0.80 1.00 2-Debenzoylpaclitaxel-2-pentenoate 0.7
0.921 1.00 Annulus Oxetane apertus, acetyl et benzoyl migravit2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (Paclitaxel affinis compositi 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 Resolutio potest esse imperfecta pro his iugis, secundum quantitates relativas praesentes;summa x1, x2, et x3 non plus quam 0,4% est.
2 Sequentia nomina chemica ad compositorum relatum Photodegradant referuntur;Oxetane anulus apertus, acetyl et benzoyl migravit;and 10,13-Bissidechainpaclitaxel;
Photodegradant
(1R,2R,4S,5S,7R,10S,11R,12S,13S,15S,16S)-2,10-diacetyloxy-5,13-dihydroxylum-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 anulus apertus, acetyl et benzoyl migravit
(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 cum (2R,3S) -2-hydroxy-3-phenyl-3-(phenylcarbonylamino) acidi propanoici, 10-ester cum (2S,3S)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino. ) Propanoicum acidum
Praeter limites paclitaxel cognatos sordes in Tabula 2, non plus quam 0.1% quarumlibet immunditiarum unica invenitur;et non plus quam 2.0% plenarum immunditiarum invenimus.
test 3 (pro materiali intitulatum ut processum fermentatum plantae cellae productum) — Si materia huic probationi obtemperat, titulus indicat convenire USP Compositiones Related Test 3 .
Solutio A-Para percolata et dejecta mixtione aque et acetonitrili (3:2).
Solutio B-Para percolata et acetonitrile dejecta.
Mobile phase-Usus mixtura variabilis Solutio A et Solutio B ut ad systema chromatographicum ordinatur.Fac si opus sit adaptationes (cf. Systema Suitability sub Chromatographia 621).
Ratio congruentia solutionis-dissolve USP Paclitaxel Impuritas Mixtura RS in acetonitrile, si opus est sonicans, solutionem obtinendam habens notam intentionem circiter 1 mg per mL.
Solution-Latina accurate ponderata quantitatem USP Paclitaxel RS in acetonitrili, si opus est sonicans, solutionem obtinendam habens notam intentionem circiter 1 mg per mL.
Expertus solutionis-Translatio circa 10 mg de Paclitaxel, accurate perpensa, ad 10-mL vasculum volumetricam.Dissolve et dilue cum acetonitrili ad volumen, si opus est sonicando et commisce.
Systema chromatographicum (cf. chromatographia 621) — chromatographum liquor 227-um detectoris instructum et 4.6-mm × 15-cm columna quae continet 3-µm fasciculum L1.Rate fluens fere 1.2 mL per minutum est.Chromatographum sic programma est.
Solutio tempus (minuta) Solutio A (%) Solutio B (%) Elution
0-28 100 0 isocratic
28-33 100®98 0®2 gradiente lineari
33-58 98®10 2®90 gradiente lineari
58-60 10 90 isocratic
60-63 10®100 90®0 gradiente lineari
63-70 100 0 isocraticChromatographum Systema aptae solutionis, et refero apicem responsionum ad procedendum directae: resolutio, R inter paclitaxel et benzyl analogia non minus quam 1.8.Chromatographa solutio Vexillifero, et refero apicem responsionum ad procedendum directae: vexillum relativum declinationis pro injectionibus replicatis non plus quam 2.0% est.[note—For the purpose of the identification, the approximate relative retention times are given in Table 3. The relativa retention times are measure versus Paclitaxel.]
Table 3
Nomen relativum retentionis terminum (%)
Propyl analog1 0.54 0.2
Cephalomanninum (compositum Paclitaxel affinis 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 Nomen chemicum huic composito affinis Propyl analog: Baccatin III 13-ester cum (2R,3S)-3-butanoylamino-2-hydroxy-3-phenylpropanoico acidum 2-2R,3S) attribuitur.
2 Sequens nomen chemicum attribuitur composito sec-Butyl analogi affinis: Baccatin III 13-ester cum (2R,3S)-2-hydroxy-3-(2-methylbutanoylamino) 3-phenylpropanoico acido.
3 Sequens nomen chemicum attribuitur compositioni affinis n-Butyl analogi: Baccatin III 13-ester cum (2S,3S)-2-hydroxy-3-(pentanoylamino)-3-phenylpropanoico acido.
4 Sequens nomen chemicum attribuitur compositioni affinis Pentyl analogi: Baccatin III 13-ester cum (2R,3S)-3-(hexanoylamino)-2-hydroxy-3-phenylpropanoico acido.
Procedure-Inject volumen (circiter 12 µL) solutionis Testis in chromatographum, chromatogrammum notare et areas ad omnes apices metire.Recipis cujusvis immunditiae in portione Paclitaxel sumpta formula:
100(ri/rU)
in quo ri- tetur cujusque responsio est;et rU summa arearum omnium alpium ex solutione Test.Praeter limites paclitaxel affines immunditias in Tabula 3, non plus quam 0.1% quarumlibet immunditiarum unica reperitur;et non plus quam 2.0% plenarum immunditiarum invenimus.
Assay-
Diluente-Para mixtionem acidi methanoli et acetici (200:1).
Mobile phase-Para percolata et devasata mixtione aquae et acetonitrili (11, 9).Fac si opus sit adaptationes (cf. Systema Suitability sub Chromatographia 621).
Praeparatio-dissolve, sonicatione, si opus sit, accurate ponderata quantitatem USP Paclitaxel RS in Diluent, et quantitatis dilue, et gradatim si opus est, cum Diluent solutionem obtinendam habens intentionem notam circa 1 mg per mL.
Praeparatio-Translatio de 10 mg Paclitaxel, accurate perpensa, ad 10-mL vasculum volumetricam.Dissolve in diluendo, sonicatione utendo, si opus est, diluto ad volumen diluendum, et permisceto.
Systema chromatographicum (vide chromatographia <621>) - chromatographum liquor 227-um detectoris instructum et 4.6-mm × 25-cm columna quae continet 5-µm fasciculum L43.Rate fluxus circiter 1.5 mL per minute est.Chromatograph in Latin Praeparatio, et refero apicem responsionum ad procedendi modo ordinati: factor tails inter 0.7 et 1.3;et vexillum relativum declinationis ad injectiones replicatas non plus quam 1.5%.
De modo procedendi-Separatim injiciunt paria volumina (circa 10 µL) praeparationis vexilliferae et praeparationis in chromatographorum, chromatogrammata notare et areas ad cacumina maiora metire.Quantitatem in mg, C47H51NO14 computa in portione Paclitaxel formula sumpta;
10C(rU/rS)
in quo C est intentio, in mg per mL, USP Paclitaxel RS in praeparatione Vulgata;and rU and rS are the apicem responses for paclitaxel obtained from the Assay preparation and the Latin preparation, respectively.