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-otu 6, 12b-diacetate, 12-benzoate, 9-ester nwere (2R,3S) -N-benzoyl-3-phenylisoserine [33069-62-4].
Paclitaxel nwere ihe na-erughị 97.0 pasent na ọ bụghị karịa 102.0 pasent nke C47H51NO14, gbakọọ na anhydrous, ihe mgbaze na-enweghị ndabere.
[Akpachara anya-Paclitaxel bụ cytotoxic.Ekwesịrị ịkpachapụ anya nke ukwuu iji gbochie iku ume nke Paclitaxel na ikpughe akpụkpọ ahụ na ya.]
Nkwakọ ngwaahịa na nchekwa - Chekwaa n'ime akpa siri ike, nke na-enweghị ọkụ, ma chekwaa na ụlọ okpomọkụ a na-achịkwa.
Ịkpọ aha-Ngosipụta aha na-egosi ụdị usoro eji emepụta ihe na ule njikọ njikọ nke ihe ahụ na-akwado.
Ụkpụrụ ntụaka USP <11>-
USP Endotoxin RS
USP Paclitaxel RS Pịa ka ilele Ọdịdị
Ngwakọta jikọrọ USP Paclitaxel A RS
Cephalomannine.
Ihe jikọrọ USP Paclitaxel B RS
10-Deacetyl-7-Epipaclitaxel.
Ngwakọta USP Paclitaxel adịghị ọcha RS
Ngwakọta nke Paclitaxel na ogige ndị metụtara ya: propyl analọg, cephalomannine, sec-butyl analọgụ, n-butyl analọg, analọg benzyl, baccatin VI, pentyl analọg, na 7-epipaclitaxel.
njirimara-
A: Infrared absorption <197K>.
B: Oge njide nke nnukwu ọnụ ọgụgụ dị elu na chromatogram nke nkwadebe Assay kwekọrọ na nke ahụ na chromatogram nke nkwadebe Standard, dị ka enwetara na Assay.
Specific ntụgharị 781S: n'etiti 49.0 na 55.0 na 20, gbakọọ na anhydrous, ihe mgbaze-free ndabere.
Ngwọta ule: 10 mg kwa ml, na methanol.
Nnwale ngụkọ microbial <61> na Nnwale maka microorganisms akọwapụtara <62>-Ngụkọta ọnụ ọgụgụ microbial aerobic anaghị agafe 100 cfu kwa g.Ọ na-emezu ihe achọrọ maka ule maka enweghị Staphylococcus aureus, Pseudomonas aeruginosa, ụdị Salmonella, na Escherichia coli.
Endotoxins nke nje bacteria 85-O nwere ọ bụghị ihe karịrị 0.4 USP Endotoxin Unit kwa mg nke paclitaxel.
Mmiri, Usoro Ic <921>: ọ bụghị karịa 4.0%.
Ihe fọdụrụ na mgbanye <281>: ọ bụghị karịa 0.2%.
Ọla dị arọ, Usoro II <231>: 0.002%.
Ngwakọta ndị emetụtara-
nwale 1 (maka ihe akpọrọ dị ka ndị dịpụrụ adịpụ site na isi mmalite) -Ọ bụrụ na ihe ahụ kwekọrọ n'ule a, akara ngosi ahụ na-egosi na ọ na-ezute Ogwe Njikọ USP 1.
Diluent- Kwadebe dị ka a gwara ya na Assay.
Ngwọta A- Kwadebe acetonitrile akọrọ na degassed.
Ngwọta B- Kwadebe mmiri akọrọ na nke ikuku.
Usoro mkpanaaka-Jiri ngwakọta agbanwe agbanwe nke Ngwọta A na Ngwọta B dịka akwadoro maka sistemụ Chromatographic.Mee mgbanwe ọ bụrụ na ọ dị mkpa (lee Dabara Sistemu n'okpuru Chromatography 621).
Ngwọta dabara adaba sistemu-Gbasa n'ụzọ ziri ezi nke USP Paclitaxel Related Compound A RS na USP Paclitaxel Related Compound B RS na methanol iji nweta ihe ngwọta n'inwe ihe dị ka 10 µg nke ọ bụla kwa ml.Nyefee 5.0 ml nke ngwọta a na flask volumetric 50-mL, gbanye ya na Diluent na olu, na mix.
Ọkọlọtọ ngwọta-agbari, site n'enyemaka nke sonication, ihe ziri ezi tụrụ ibu nke USP Paclitaxel RS na diluent, na itughari quantitatively, na stepwise ma ọ bụrụ na ọ dị mkpa, na diluent nweta ngwọta na-enwe a maara ịta nke banyere 5 µg kwa ml.
Ngwọta nwale-Jiri nkwadebe Assay.
Usoro Chromatographic (lee Chromatography <621>) -Kromatograph mmiri mmiri nwere ihe nchọta 227-nm yana kọlụm 4.6-mm × 25-cm nke nwere ngwugwu 5-µm L43.Ọnụego ya bụ ihe dịka 2.6 ml kwa nkeji.A na-edobe okpomoku kọlụm na 30. A na-ahazi chromatograph dị ka ndị a.
Oge (nkeji) Ngwọta A (%) Ngwọta B (%) Elution
0–35 35 65 isocratic
35–60 35®80 65®20 gradient linear
60–70 80®35 20®65 gradient ahịrị
70-80 35 65 isocraticChromatograph the System suitability solution, ma dekọọ nzaghachi kacha elu dị ka akwadoro maka Usoro: oge ​​njide dị n'ihe gbasara 0.78 maka paclitaxel metụtara compound A na 0.86 maka paclitaxel metụtara compound B (n'ihe metụtara oge njide maka paclitaxel nwetara site na ya. ngwọta ule);na mkpebi, R, n'etiti paclitaxel metụtara compound A na paclitaxel metụtara compound B erughị 1.0.Chromatograph the Standard solution, wee dekọọ nzaghachi kacha elu dị ka akwadoro maka Usoro: ụkpụrụ agbakwunyere maka injections oyiri abụghị ihe karịrị 2.0%.
Usoro-Tinye otu olu (ihe dị ka 15 µL) nke ngwọta Nnwale n'ime chromatograph, dekọọ chromatogram, ma tụọ mpaghara maka ọnụ ọgụgụ kacha elu.Gbakọọ pasent nke adịghị ọcha ọ bụla na mpaghara Paclitaxel nke usoro a were were:
100 (Fri / rU)
nke F bụ ihe nzaghachi nzaghachi maka ọnụ ọgụgụ adịghị ọcha ọ bụla (lee Tebụl 1 maka ụkpụrụ);ri bụ ebe kacha elu maka adịghị ọcha onye ọ bụla;na rU bụ mpaghara kacha elu maka paclitaxel.
Tebụl 1
Oge Njide Ọdịnala Ihe Nzaghachi Ọdịnaya (F) Oke Aha (%)
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 (ihe metụtara Paclitaxel A) a11
0.78 1.26 2'',3''-Dihydrocephalomannine a21
0.86 1.00 10-Deacetyl-7-epipaclitaxel (ihe metụtara Paclitaxel B) 0,5
1.10 1.00 Benzyl analọgụ3 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
1 Mkpebi nwere ike ezughị oke maka ọnụ ọgụgụ ndị a, dabere na ọnụọgụ ndị dị ugbu a;Nchikota nke a1 na a2 abụghị ihe karịrị 0.5%.
2 Mkpebi nwere ike ezughị oke maka ọnụ ọgụgụ ndị a, dabere na ọnụọgụ ndị dị ugbu a;Nchikota nke b1 na b2 abụghị ihe karịrị 0.5%.
3 A na-ekenye aha kemịkalụ na-esote ya na ogige metụtara ya, analọg benzyl:Baccatin III 13-ester na (2R,3S) -2-hydroxy-3-phenyl-3- (2-phenylacetylamino)propanoic acid.
Na mgbakwunye na ịgafeghị oke maka adịghị ọcha metụtara paclitaxel na Tebụl 1, a na-ahụ ihe karịrị 0.1% nke adịghị ọcha ọ bụla ọzọ;na ọ bụghị ihe karịrị 2.0% nke mkpokọta adịghị achọta.
nwale 2 (maka ihe akpọrọ dị ka usoro semisynthetic mepụtara) - Ọ bụrụ na ihe ahụ kwekọrọ n'ule a, akara ngosi ahụ na-egosi na ọ na-ezute ogige USP metụtara Test 2.
Diluent-Jiri acetonitrile.
Ngwọta A-Jiri ngwakọta nke mmiri na acetonitrile (3:2) gbakọrọ na nke ikuku.
Ngwọta B-Jiri acetonitrile akọrọ na degassed.
Usoro mkpanaaka-Jiri ngwakọta agbanwe agbanwe nke Ngwọta A na Ngwọta B dịka akwadoro maka sistemụ Chromatographic.Mee mgbanwe ọ bụrụ na ọ dị mkpa (lee Dabara Sistemu n'okpuru Chromatography 621).
Ngwọta dabara adaba nke sistemu-Gbasa n'ụzọ ziri ezi nke USP Paclitaxel RS na USP Paclitaxel Related Compound B RS na diluent, na-ama jijiji ma na-eme mkpọtụ ma ọ bụrụ na ọ dị mkpa, iji nweta ihe ngwọta ebe amaara ọkwa nke ihe dịka 0.96 mg na 0.008 mg kwa ml, n'otu n'otu.
Nnwale ule - Nyefee ihe dị ka 10 mg nke Paclitaxel, tụọ ya nke ọma, na flask volumetric 10-mL, gbazee ma gbanye ya na Diluent na olu, na-ama jijiji ma na-emegharị ma ọ bụrụ na ọ dị mkpa, na mix.
Usoro Chromatographic (lee Chromatography 621) - chromatograph mmiri mmiri nwere ihe nchọta 227-nm yana kọlụm 4.6mm × 15-cm nke nwere ngwugwu 3-µm L1.Onu ogugu a bu ihe dika 1.2 ml kwa nkeji.A na-edobe okpomọkụ kọlụm na 35. A na-ahazi chromatograph dị ka ndị a.
Oge (nkeji) Ngwọta A (%) Ngwọta B (%) Elution
0-20 100 0 isocratic
20-60 100®10 0®90 gradient ahịrị
60-62 10®100 90®0 gradient ahịrị
62-70 100 0 isocraticChromatograph the System suitability solution, ma dekọọ nzaghachi kacha elu dị ka akwadoro maka Usoro: oge ​​njide nke ikwu bụ ihe dịka 0.94 maka paclitaxel metụtara compound B na 1.0 maka paclitaxel;mkpebi, R, n'etiti paclitaxel metụtara compound B na paclitaxel abụghị ihe na-erughị 1.2;na ndị ikwu ọkọlọtọ ndiiche maka oyiri injections abụghị ihe karịrị 2.0%.
Usoro-iche iche, gbanye nha nha nha nha (ihe dịka 15 µL) nke ihe ngwọta na ngwọta ule n'ime chromatograph, dekọọ chromatograms, ma tụọ mpaghara maka ọnụ ọnụ ọnụ.Na-eleghara ọnụ ọgụgụ kasị elu ọ bụla n'ihi diluent.Gbakọọ pasent nke adịghị ọcha ọ bụla na mpaghara Paclitaxel nke usoro a were were:
100 (Fri / s)
nke F bụ ihe nzaghachi nzaghachi maka adịghị ọcha ọ bụla (lee Tebụl 2 maka ụkpụrụ);ri bụ ebe kachasị elu maka adịghị ọcha ọ bụla enwetara site na ngwọta ule;na rs bụ nchikota nke mpaghara nke ọnụ ọgụgụ kasị elu niile enwetara site na ngwọta ule.
Tebụl 2
Oge Njide Ọdịnala Ihe Nzaghachi Ọdịnaya (F) Oke Aha (%)
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 meghere, acetyl na benzoyl kwagara2 x1
0.921 1.00 10-Acetoacetylpaclitaxel x2
0.941 1.00 10-Deacetyl-7-epipaclitaxel (ihe metụtara 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 Mkpebi nwere ike ezughị oke maka ọnụ ọgụgụ ndị a, dabere na ọnụọgụ ndị dị ugbu a;Nchikota nke x1, x2, na x3 abụghị ihe karịrị 0.4%.
2 A na-ekenye aha kemịkal ndị a na ogige ndị metụtara Photodegradant;Oxetane mgbanaka meghere, acetyl na benzoyl kwagara;na 10,13-Bissidechainpaclitaxel:
Onye na-ese foto
(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 mgbanaka meghere, acetyl na benzoyl kwagara
(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 na (2R,3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino) propanoic acid, 10-ester na (2S,3S) -2-hydroxy-3-phenyl-3- (phenylcarbonylamino). ) propanoic acid
Na mgbakwunye na ịgafeghị oke maka adịghị ọcha metụtara paclitaxel na tebụl 2, ọ bụghị ihe karịrị 0.1% nke adịghị ọcha ọ bụla ọzọ ka a hụrụ;na ọ bụghị ihe karịrị 2.0% nke mkpokọta adịghị achọta.
nwale 3 (maka ihe akpọrọ dị ka usoro mkpụrụ ndụ ihe ọkụkụ na-emepụta) - Ọ bụrụ na ihe ahụ kwekọrọ n'ule a, akara ngosi na-egosi na ọ na-ezute ogige USP metụtara Test 3.
Ngwọta A- Kwadebe ngwakọta nke mmiri na acetonitrile (3:2).
Ngwọta B- Kwadebe acetonitrile akọrọ na degassed.
Usoro mkpanaaka-Jiri ngwakọta agbanwe agbanwe nke Ngwọta A na Ngwọta B dịka akwadoro maka sistemụ Chromatographic.Mee mgbanwe ọ bụrụ na ọ dị mkpa (lee Dabara Sistemu n'okpuru Chromatography 621).
Ngwọta dabara adaba nke sistemu - Gbanyụọ USP Paclitaxel adịghị ọcha ngwakọta RS na acetonitrile, sonicating ma ọ bụrụ na ọ dị mkpa, iji nweta ihe ngwọta na-enwe a maara ịta nke banyere 1 mg kwa ml.
Ọkọlọtọ ngwọta-Kwụsị n'ụzọ ziri ezi nke USP Paclitaxel RS na acetonitrile, sonicating ma ọ bụrụ na ọ dị mkpa, iji nweta ngwọta na-enwe a maara ịta nke banyere 1 mg kwa ml.
Ngwọta nnwale - Nyefee ihe dịka 10 mg nke Paclitaxel, tụọ ya nke ọma, gaa na flask volumetric 10-mL.Gbanyụọ ma gbanye ya na acetonitrile ka ọ bụrụ olu, na-emegharị ma ọ bụrụ na ọ dị mkpa, ma gwakọta ya.
Usoro Chromatographic (lee Chromatography 621) - chromatograph mmiri mmiri nwere ihe nchọta 227-nm yana kọlụm 4.6mm × 15-cm nke nwere ngwugwu 3-µm L1.Onu ogugu a bu ihe dika 1.2 ml kwa nkeji.A na-ahazi chromatograph dị ka ndị a.
Oge (nkeji) Ngwọta A (%) Ngwọta B (%) Elution
0-28 100 0 isocratic
28-33 100®98 0®2 gradient ahịrị
33–58 98®10 2®90 gradient ahịrị
58-60 10 90 isocratic
60-63 10®100 90®0 gradient ahịrị
63-70 100 0 isocraticChromatograph nke dabara adaba sistemu, wee dekọọ nzaghachi kacha elu dị ka akwadoro maka Usoro: mkpebi, R, n'etiti paclitaxel na benzyl analọgụ erughị 1.8.Chromatograph the Standard solution, wee dekọọ nzaghachi kacha elu dị ka akwadoro maka Usoro: ụkpụrụ agbakwunyere maka injections oyiri abụghị ihe karịrị 2.0%.[ndeba ama-Maka ebumnuche nke njirimara kachasị elu, a na-enye oge njigide oge dị nso na Tebụl 3. A na-atụ oge njide nke ikwu na Paclitaxel.]
Tebụl 3
Oke Oge Njido Aha (%)
Analọgụ Propyl1 0.54 0.2
Cephalomannine (ihe metụtara Paclitaxel A) 0.76 0.5
sec-Butyl analọg2 0.81 0.2
n-Butyl analọgụ3 0.89 0.1
Ihe analog nke Benzyl 1.10 0.4
Baccatin VI 1.23 0.2
Pentyl analog 1.31 0.2
7-Epipaclitaxel 1.51 0.4
1 A na-ekenye aha kemịkalụ na-esote Propyl analọgụ:Baccatin III 13-ester nwere (2R,3S) -3-butanoylamino-2-hydroxy-3-phenylpropanoic acid.
2 A na-ekenye aha kemịkalụ na-esote sec-Butyl analọgụ metụtara ya:Baccatin III 13-ester na (2R,3S) -2-hydroxy-3- (2-methylbutanoylamino) -3-phenylpropanoic acid.
3 A na-ekenye aha kemịkal na-esote n-Butyl analọgụ metụtara ya:Baccatin III 13-ester nwere (2S,3S) -2-hydroxy-3-(pentanoylamino) -3-phenylpropanoic acid.
4 A na-ekenye aha kemịkalụ a na njikọ Pentyl analọg:Baccatin III 13-ester nwere (2R,3S)-3-(hexanoylamino) -2-hydroxy-3-phenylpropanoic acid.
Usoro-Tinye otu olu (ihe dị ka 12 µL) nke ngwọta Nnwale n'ime chromatograph, dekọọ chromatogram, ma tụọ mpaghara maka ọnụ ọnụ niile.Gbakọọ pasent nke adịghị ọcha ọ bụla na mpaghara Paclitaxel nke usoro a were were:
100 (ri / rU)
nke ri bụ nzaghachi nke onye ọ bụla adịghị ọcha;na rU bụ nchikota nke mpaghara niile elu nke enwetara site na ngwọta ule.Na mgbakwunye na ịgafeghị oke maka adịghị ọcha metụtara paclitaxel na Tebụl 3, ọ bụghị karịa 0.1% nke adịghị ọcha ọ bụla ọzọ ka a hụrụ;na ọ bụghị ihe karịrị 2.0% nke mkpokọta adịghị achọta.
Nyocha -
Diluent- Kwadebe ngwakọta nke methanol na acetic acid (200: 1).
Usoro mkpanaaka - Kwadebe ngwakọta mmiri na acetonitrile akọrọ na nke gbazere (11:9).Mee mgbanwe ọ bụrụ na ọ dị mkpa (lee Dabara Sistemu n'okpuru Chromatography 621).
Standard nkwadebe-gbari, iji sonication ma ọ bụrụ na ọ dị mkpa, ihe ziri ezi tụrụ ibu nke USP Paclitaxel RS na diluent, na itughari quantitatively, na stepwise ma ọ bụrụ na ọ dị mkpa, na diluent nweta ngwọta na-enwe a maara ịta nke banyere 1 mg kwa ml.
Nkwadebe nyocha - Nyefee ihe dị ka 10 mg nke Paclitaxel, tụọ ya nke ọma, gaa na flask volumetric 10-mL.Gbanyụọ na diluent, na-eji sonication ma ọ bụrụ na ọ dị mkpa, gbanye ya na diluent ka ọ bụrụ olu, na mix.
Usoro Chromatographic (lee Chromatography <621>) -Kromatograph mmiri mmiri nwere ihe nchọta 227-nm yana kọlụm 4.6-mm × 25-cm nke nwere ngwugwu 5-µm L43.Onu ogugu a bu ihe dika 1.5 ml kwa nkeji.Chromatograph the Standard nkwadebe, na dekọọ nzaghachi kasị elu dị ka a na-eduzi maka Usoro: ihe ọdụdụ dị n'etiti 0.7 na 1.3;na ndị ikwu ọkọlọtọ ndiiche maka oyiri injections abụghị ihe karịrị 1.5%.
Usoro-iche iche nha nha nha (ihe dị ka 10 µL) nke nkwadebe ọkọlọtọ na nkwadebe Assay n'ime chromatograph, dekọọ chromatograms, wee tụọ mpaghara maka ọnụ ọgụgụ ndị bụ isi.Gbakọọ ọnụọgụ, na mg, nke C47H51NO14 n'ime akụkụ nke Paclitaxel nke usoro a bu:
10C (rU / rS)
nke C bụ ntinye uche, na mg kwa ml, nke USP Paclitaxel RS na nkwadebe Standard;na rU na rS bụ nzaghachi kachasị elu maka paclitaxel nwetara site na nkwadebe Assay na Standard nkwadebe, n'otu n'otu.