{"id":6209,"date":"2022-09-18T11:40:30","date_gmt":"2022-09-18T07:10:30","guid":{"rendered":"http:\/\/arasto.com\/product\/erlotinib\/"},"modified":"2023-05-08T13:32:38","modified_gmt":"2023-05-08T10:02:38","slug":"erlotinib","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/erlotinib\/","title":{"rendered":"Erlotinib"},"content":{"rendered":"

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

(In-house)<\/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: Erlotinib Hydrochloride\u00a0 (Brand Name: Tarceva, Roche, Switzerland)<\/p>\n

    Compendial name: Erlotinib Hydrochloride<\/p>\n

    Chemical name:\u00a0\u00a0 \u00a0N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine<\/p>\n

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

    CAS Registry Number: [183319-69-9]<\/p>\n

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

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

    <\/p>\n

    . HCl<\/p>\n

    Empirical formula: C22<\/sub>H23<\/sub>N3<\/sub>O4<\/sub>.HCl
    \nMolecular Weight: 429.94 g\/mol<\/p>\n

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

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

      Erlotinib hydrochloride is a white to off-while crystalline substance. It is soluble in water and polar organic solvents such as DMSO, DMF and methanol.\u00a0 Erlotinib is an orally administered agent used for the treatment of advanced-stage non-small cell lung cancer (NSCLC) CLC(http:\/\/www.tarceva.com\/patient\/ considering\/index.jsp<\/a>). The pKa valve of Erlotinib has been reported to be 5.42 (http:\/\/www.roche-australia.com \/fmfiles\/re7229005\/downloads\/oncology\/ tarceva-pi.pdf).\u00a0 Erlotinib hydrochloride is stable in acid or base (see Stability Studies). LD50<\/sub>\u00a0of Erlotinib hydrochloride has been reported (<5003 mg\/kg oral rat; <1000 mg\/kg; dermal rat\u00a0http:\/\/www.ehso.emory.edu\/content-guidelines<\/a>\u00a0\/ChemicalSafetyNOIGuideline.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.\u00a0Each SRS has undergone extensive characterization (IR, UV, 1<\/sup>HNMR, 13<\/sup>CNMR. Mass Spec) and determination of its purity and assay (HPLC).\u00a0For 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).\u00a0For specification of those products that do not have a monograph (known as House Primary Standard), we compare their UV \u03b5 or \u05d2 \/max<\/sub>, IR major absorptions, 1HNMR d (ppm) , 13 CNMR d (ppm) or HPLC retention time with values reported in the chemical literature for these compounds.<\/p>\n

      <\/p>\n

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

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

        Primary Reference Standard for erlotinib is not available from United States Pharmacopoeia. We will use a House Primary Standard (previously referred to as Working Standard) for direct control of all batches of erlotinib.<\/p>\n

        As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3)House Primary \u00a0Standards, 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 House Primary Standard of the API erlotinib has undergone extensive characterization (UV, IR,\u00a01<\/sup>\u00a0H NMR,\u00a013<\/sup>C NMR, Mass Spec) to assure its structure, assay and purity (HPLC and\/or titration) and specification .<\/p>\n

        The House Primary Standard for erlotinib was produced from a released batch of erlotinib 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.\u00a0It was crystallized twice more to ensure high level of purity.<\/p>\n

         <\/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\n
        Product:<\/strong> Erlotinib Hydrochloride<\/td>\nCAS No.: <\/strong>183319-69-9<\/a><\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-379-00<\/td>\n<\/tr>\n
        Issue Date: <\/strong>Apr, 2023<\/td>\nValid up to:<\/strong> Apr, 2024<\/td>\nReference: <\/strong>In-house<\/td>\n<\/tr>\n
        Tests<\/strong><\/td>\n\n

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

        Appearance<\/td>\nWhite to off white powder.<\/td>\n<\/tr>\n
        Solubility<\/td>\nSlightly soluble in methanol. Insoluble in acetonitrile and acetone.<\/td>\n<\/tr>\n
        Identification<\/td>\nInfrared Absorption<\/td>\n<\/tr>\n
        X-ray diffraction<\/td>\nForm A<\/td>\n<\/tr>\n
        Loss on Drying<\/td>\nNMT 1.0%<\/td>\n<\/tr>\n
        Residue on Ignition<\/td>\nNMT 0.1%<\/td>\n<\/tr>\n
        Heavy metals<\/td>\nNMT 20ppm<\/td>\n<\/tr>\n
        HCl content<\/td>\nBetween 8.3% to 8.7%<\/td>\n<\/tr>\n
        Residual solvents<\/td>\nToluene: Max. 890 ppm (Class II)<\/p>\n

        Isopropanol: Max. 5000 ppm (Class \u0428)<\/p>\n

        Ethyl acetate: Max. 5000ppm (Class \u0428)<\/td>\n<\/tr>\n

        Related substances (HPLC)<\/td>\nErlotinib. HCl Related Compound A: NMT 0.10%<\/p>\n

        Erlotinib. HCl Related Compound B: NMT 0.10%<\/p>\n

        Erlotinib. HCl Related Compound C: NMT 0.10%<\/p>\n

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

        Total impurities: NMT 0.5%<\/td>\n<\/tr>\n

        Assay (HPLC)<\/td>\n98.0% to 102.0% (calculated on dried basis)<\/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 tight containers. Store at controlled room temperature.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

        Description (In-house) Drug Substance General Information (ICH 3.2.S.1) 1.1. Nomenclature (ICH 3.2.S.1.1) International non-proprietary name: Erlotinib Hydrochloride\u00a0 (Brand Name: Tarceva, Roche, Switzerland) Compendial name: Erlotinib Hydrochloride Chemical name:\u00a0\u00a0 \u00a0N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine Arasto\u2019s code: ERL CAS Registry Number: [183319-69-9] 1. Drug Substance General Information (ICH 3.2.S.1) 1.2 Structure (ICH 3.2.S.1.2) . HCl Empirical formula: C22H23N3O4.HCl Molecular Weight: 429.94 […]<\/p>\n","protected":false},"featured_media":7926,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[73],"product_tag":[],"class_list":["post-6209","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-73"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6209","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=6209"}],"version-history":[{"count":1,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6209\/revisions"}],"predecessor-version":[{"id":7928,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6209\/revisions\/7928"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7926"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6209"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6209"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6209"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}