{"id":6207,"date":"2022-09-18T11:39:12","date_gmt":"2022-09-18T07:09:12","guid":{"rendered":"http:\/\/arasto.com\/product\/docetaxel\/"},"modified":"2023-05-08T13:53:21","modified_gmt":"2023-05-08T10:23:21","slug":"docetaxel","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/docetaxel\/","title":{"rendered":"Docetaxel"},"content":{"rendered":"

Description<\/strong><\/p>\n

(USP 44)<\/p>\n

    \n
  1. Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/li>\n<\/ol>\n

    1.1. Nomenclature (ICH 3.2.S.1.1)<\/strong><\/p>\n

    International non-proprietary name: Docetaxel (Brand Name: Taxotere, Sanofi Oncology (Sanofi), USA<\/p>\n

    Compendial name: Docetaxel<\/p>\n

    Chemical name: 1,7\u03b2,10\u03b2-trihydroxy-9-oxo-5\u03b2,20-epoxytax-11-ene-2\u03b1,4,13\u03b1-triyl 4-acetate 2-benzoate 13-{(2R<\/em>,3S<\/em>)-3-[(tert<\/em>-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate}<\/p>\n

    Arasto\u2019s code: DOC<\/p>\n

    CAS Registry Number: [114977-28-5]<\/p>\n

      \n
    1. Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/li>\n<\/ol>\n

      1.2 Structure (ICH 3.2.S.1.2)<\/strong><\/p>\n

      <\/p>\n

      3H2<\/sub>O<\/p>\n

      Empirical formula:\u00a0C<\/a>43<\/sub>H<\/a>53<\/sub>N<\/a>O<\/a>14.\u00a0<\/sub>3H2<\/sub>O<\/p>\n

      Molecular Weight: 861.90 g\/mol<\/p>\n

       <\/p>\n

      1. Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/p>\n

      1.3. General Properties (ICH 3.2.S.1.3)<\/strong><\/p>\n

      Docetaxel is a white crystalline substance. It is practically insoluble in water and soluble in polar organic.\u00a0 Docetaxel is used in the form of injection concentrate for the treatment of breast cancer, advanced non-small cell lung cancer, metastatic androgen-independent prostate cancer, advanced gastric\/GE junction cancer, locally advanced head and neck cancer (.http:\/\/www.taxotere.com\/). Its log P is 4.26\u00a0(<\/strong>http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR-Public _assessment_report \/human\/001107\/WC500073418.pdf<\/a>).\u00a0\u00a0<\/strong>Docetaxel is not stable in acid or base (see Stability Studies and EP 1978953A1). LD50<\/sub>\u00a0of docetaxel has been reported ( > 2000 mg\/kg oral\u00a0 rat; 138 mg\/kg IV mouse,\u00a0http:\/\/www.pfizer.com\/files\/products\/material safety data\/ PZ00906<\/a>\u00a0.pdf).<\/p>\n

      The determination of purity and assay of APIs require comparison of the product with their respective Reference Standards (RS) and Related Compounds (RC or known impurities).\u00a0 Accordingly, ICH regulations on the purity and assay of reference standard and related compounds are clearly defined and must be followed by drug substance and drug product manufacturers.<\/p>\n

      According to ICH Q7, 11.1 there are 3 types of standards.\u00a0 This is summarized in the following chart and discussed in detail below.<\/p>\n

      <\/p>\n

      The impurities provided in the following table represent Secondary Reference Standards (SRS) that are prepared in-house by synthesis or by isolation. Each SRS has undergone extensive characterization ( IR, UV, 1HNMR, 13CNMR. Mass Spec) and determination of its purity and assay (HPLC). For specification of the SRS of those products that have a monograph, the SRS is compared with a pharmacopoeia Primary Reference Standard (UV, HPLC retention time). For specification of those products that do not have a monograph (known as House Primary Standard), we compare their UV \u03b5 or \u05d2 \/max<\/sub>\u00a0, IR major absorptions, 1<\/sup>HNMR d (ppm) , 13<\/sup> CNMR d (ppm) or HPLC retention time with values reported in the chemical literature for these compounds.<\/p>\n

      <\/p>\n

       <\/p>\n

        \n
      1. Primary and Secondary Reference Standard (ICH 3.2.S.5)<\/strong><\/li>\n<\/ol>\n

        \u00a0\u00a05.1.\u00a0Active Pharmaceutical Ingredient<\/strong><\/p>\n

        Primary Reference Standard for docetaxel is available from United States Pharmacopoeia. We will use a Secondary Reference Standard (previously referred to as Working Standard) for direct control of all batches of docetaxel.<\/p>\n

        As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3)the Secondary Reference Standards, which include the API and its Related Compounds,\u00a0must be examined for their proof of structure (characterization), assay and purity and specification (identification by comparison). Furthermore, ICH Guideline on the Preparation of Common Technical Document (Q4M) requires that the data obtained from characterization, assay and purity and specification must be included in section 3.2.S.3.2 for Related Compounds (already discussed in that section) and section 3.2.S.5 of the DMF for the API.\u00a0To this end, the Secondary Reference Standards of the API docetaxel has undergone extensive characterization (UV, IR,\u00a01<\/sup>\u00a0H NMR,\u00a013<\/sup>C NMR, and Mass Spec) to assure its structure, assay and purity (HPLC and\/or titration) and specification (comparison of its HPLC retention time and UV \u05d2 \/max<\/sub>\u00a0with USP Primary Reference Standard.<\/p>\n

        The Secondary Reference Standard for docetaxel was produced from a released batch of docetaxel by subjecting it to an additional crystallization from the final solvent system used in the production of the API to avoid the possibility of other polymorph formation.<\/p>\n

        SPECIFICATION OF ANALYSIS<\/h1>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
        Product:<\/strong> Docetaxel. 3H2<\/sub>O<\/td>\nCAS No.: <\/strong>148408-66-6<\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-378-00<\/td>\n<\/tr>\n
        Issue Date: <\/strong>Apr, 2023<\/td>\nValid up to:<\/strong> Apr, 2024<\/td>\nReference: <\/strong>USP44<\/td>\n<\/tr>\n
        Tests<\/strong><\/td>\n\n

        Specifications<\/h2>\n<\/td>\n<\/tr>\n

        Description<\/td>\nWhite or almost white, crystalline powder.<\/td>\n<\/tr>\n
        Solubility<\/td>\nFreely Soluble in acetone; soluble in methanol; practically insoluble in water.<\/td>\n<\/tr>\n
        Identification<\/td>\nA: Infrared Spectroscopy.<\/p>\n

        B: the retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the assay.<\/td>\n<\/tr>\n

        Optical Rotation<\/td>\n-39\u02da to -41\u02da calculated on the anhydrous and solvent free basis.<\/td>\n<\/tr>\n
        Water determination<\/td>\n5.0% to 7.0%.<\/td>\n<\/tr>\n
        Residue on ignition<\/td>\nNMT 0.1%<\/td>\n<\/tr>\n
        Residual Solvents<\/td>\nAcetone: NMT 5000 ppm (Class III)<\/p>\n

        Ethanol: NMT 5000 ppm (Class III)<\/p>\n

        Ethyl acetate: NMT 5000 ppm (Class III)<\/p>\n

        Dichloromethane: NMT 600 ppm (Class II)<\/p>\n

        Methanol: NMT 3000 ppm (Class II)<\/p>\n

        Toluene: NMT 890 ppm (Class II)<\/p>\n

        Chloroform: NMT 60ppm (Class II)<\/p>\n

        Heptane: NMT 5000 ppm (Class III)<\/td>\n<\/tr>\n

        Organic impurities (procedure 1)<\/td>\n10-Deacetyl baccatin: NMT 0.15%<\/p>\n

        N-Formyl impurity: NMT 0.15%<\/p>\n

        2-Debenzoxyl 2-pentenoyl docetaxel: NMT 0.5%<\/p>\n

        6-Oxodocetaxel: NMT 0.3%<\/p>\n

        4-Epidocetaxel: NMT 0.3%<\/p>\n

        4-Epi-6-oxodocetaxel: NMT 0.2%<\/p>\n

        6-Dichloroethoxycarbonyl docetaxel: NMT 0.15%<\/p>\n

        Any unspecified impurity: NMT 0.10%<\/p>\n

        Total impurities: NMT 1.0%<\/td>\n<\/tr>\n

        Assay<\/td>\nNLT 97.5% and NMT 102.0% (on the anhydrous and solvent-free basis)<\/td>\n<\/tr>\n
        Microbial limit test(MLT)<\/p>\n

        Total aerobic Microbial count<\/p>\n

        Total yeast and moulds count<\/p>\n

        Test of pathogen<\/p>\n

        1. E. Coli<\/p>\n

        2. P.aeruginosa<\/p>\n

        3. Salmonella species<\/p>\n

        4. S. aureus<\/p>\n

        Endotoxin Limit<\/td>\n

        		NMT 100 CFU\/g<\/p>\n

        NMT 10 CFU\/g<\/p>\n

        Should be Absent<\/p>\n

        Should be Absent<\/p>\n

        Should be Absent<\/p>\n

        Should be Absent<\/p>\n

        NMT 0.4 EU\/mg<\/td>\n<\/tr>\n

        Prepared by:<\/strong> M. Shahbazi, B.Sc.Chem.<\/td>\nChecked by:<\/strong> A. Forghani, B.Sc.Chem.<\/td>\n<\/tr>\n
        Approved by:<\/strong> F. Javadizadeh, M.Sc.Chem.<\/td>\n<\/tr>\n
        Storage:<\/strong> Preserve in well-closed, light resistant containers, and storage at room temperature or between 2\u00b0 C and 8\u00b0 C.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

        Description (USP 44) Drug Substance General Information (ICH 3.2.S.1) 1.1. Nomenclature (ICH 3.2.S.1.1) International non-proprietary name: Docetaxel (Brand Name: Taxotere, Sanofi Oncology (Sanofi), USA Compendial name: Docetaxel Chemical name: 1,7\u03b2,10\u03b2-trihydroxy-9-oxo-5\u03b2,20-epoxytax-11-ene-2\u03b1,4,13\u03b1-triyl 4-acetate 2-benzoate 13-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate} Arasto\u2019s code: DOC CAS Registry Number: [114977-28-5] Drug Substance General Information (ICH 3.2.S.1) 1.2 Structure (ICH 3.2.S.1.2) 3H2O Empirical formula:\u00a0C43H53NO14.\u00a03H2O Molecular Weight: […]<\/p>\n","protected":false},"featured_media":7949,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[73],"product_tag":[],"class_list":["post-6207","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-73"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6207","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/comments?post=6207"}],"version-history":[{"count":1,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6207\/revisions"}],"predecessor-version":[{"id":7951,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6207\/revisions\/7951"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7949"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6207"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6207"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6207"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}