{"id":6116,"date":"2022-09-18T12:09:45","date_gmt":"2022-09-18T07:39:45","guid":{"rendered":"http:\/\/arasto.com\/product\/amitriptyline-hcl\/"},"modified":"2023-05-06T12:46:56","modified_gmt":"2023-05-06T09:16:56","slug":"amitriptyline-hcl","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/amitriptyline-hcl\/","title":{"rendered":"Amitriptyline HCl"},"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:\u00a0 Amitriptyline hydrochloride (Brand Name: Elavil, Endep, and Vanatrip)<\/p>\n

    Compendial name:\u00a0 Amitriptyline hydrochloride<\/p>\n

    Chemical name:1-Propanamine, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-\u00a0 N,N-dimethyl Hydrochloride,\u00a0 10,11-Dihydro-N,N-dimethyl-5H-dibenzo [a,d]cycloheptene-\u0394-5, \u03b3-propylamine Hydrochloride<\/p>\n

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

    CAS Registry Number: [549-18-8]<\/p>\n

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

      \u00a01.2. Structure (ICH 3.2.S.1.2)<\/strong><\/p>\n

      <\/p>\n

      Empirical formula: C20<\/sub>H23<\/sub>N.HCl<\/p>\n

      Molecular Weight: 313.86 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

        Amitriptyline hydrochloride is a tricyclic antidepressant.\u00a0 It is orally administered for the It is a white to off-white crystalline substance.\u00a0 It is administered orally for the treatment of depression.\u00a0 Amitriptyline hydrochloride is soluble in water and polar organic solvents such as alcohols, DMF and DMSO.\u00a0 The pKa<\/sub>\u00a0of the secondary amine function is 9.4 (K. Florey, Ed.,\u00a0Analytical Profiles of Drug Substances<\/em>, Vol. 3,\u00a0 New York, Academic Press, 1974). Its log P has been reported to be 4.9 (S.H.Hansen, S.Pedersen-Bjergraad, K.E.Rasmusse,\u00a0Introduction to Pharmaceutical Analysis<\/em>,\u00a02012,<\/strong>\u00a0John Wiley & Sons, Ltd. UK, p.300). Amitriptyline hydrochloride is inert to acid and base (see Stability Studies).\u00a0 Acute oral LD50<\/sub>: has been reported to be 140 mg\/kg in mouse and 240 mg\/kg in rat (see\u00a0http:\/\/www.sciencelab.com\/ mMSDS-amitriptyline_hydrochloride<\/a>).<\/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.\u00a0 Each SRS has undergone extensive characterization ( IR, UV, 1HNMR, 13CNMR. Mass Spec) and determination of its purity and assay (HPLC).\u00a0 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).\u00a0 For specification of those products that do not \u00a0have a monograph (known as \u00a0House Primary Standard), we \u00a0compare their UV \u03b5 or \u05d2\/max<\/sub>\u00a0, IR major absorptions, 1HNMR d (ppm) , 13 CNMR \u00a0d (ppm) or HPLC retention time with values reported in the chemical literature for these compounds.<\/p>\n

        <\/strong><\/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 Amitriptyline hydrochloride is available from United States Pharmacopoeia. We will use a Secondary Reference Standard (also known as House Standard or Working Standard) for direct control of all batches of amitriptyline hydrochloride.<\/p>\n

          As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3) the Secondary Reference Standards must be examined for their identity by proof of structure (characterization), assay and purity and specification.\u00a0Furthermore, 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 and section 3.2.S.5 of the DMF for the API.\u00a0To this end, the Secondary Reference Standards of the API amitriptyline hydrochloride has undergone extensive characterization (UV, IR,\u00a01<\/sup>\u00a0H NMR,\u00a013<\/sup>C NMR, Mass Spec) to assure their identity, 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 amitriptyline HCl was produced from a released batch of amitriptyline HCl 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
          Product:<\/strong> Amitriptyline Hydrochloride<\/td>\nCAS No.:<\/strong> 549-18-8<\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-369-00<\/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 practically white, odorless or practically odorless, crystalline powder or small crystals.<\/td>\n<\/tr>\n
          Solubility<\/td>\nFreely soluble in water, in alcohol, in chloroform, and in methanol; insoluble in ether.<\/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.<\/p>\n

          C: Test of Chloride.<\/td>\n<\/tr>\n

          pH<\/td>\n5.0-6.0 (solution of 10 mg\/mL in water)<\/td>\n<\/tr>\n
          Loss on drying<\/td>\nNMT 0.5%<\/td>\n<\/tr>\n
          Residue on ignition<\/td>\nNMT 0.1%<\/td>\n<\/tr>\n
          Residual Solvents<\/td>\nToluene: NMT 890 ppm (Class II)<\/td>\n<\/tr>\n
          Organic Impurities (HPLC)<\/td>\nAmitriptyline related compound A: NMT 0.05%<\/p>\n

          Amitriptyline related compound B: NMT 0.15%<\/p>\n

          Nortriptyline: NMT 0.15%<\/p>\n

          Cyclobenzaprine: NMT 0.15%<\/p>\n

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

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

          Assay (HPLC)<\/td>\n98.0% to 102.0% (on the 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 well-closed containers.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

          \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:\u00a0 Amitriptyline hydrochloride (Brand Name: Elavil, Endep, and Vanatrip) Compendial name:\u00a0 Amitriptyline hydrochloride Chemical name:1-Propanamine, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-\u00a0 N,N-dimethyl Hydrochloride,\u00a0 10,11-Dihydro-N,N-dimethyl-5H-dibenzo [a,d]cycloheptene-\u0394-5, \u03b3-propylamine Hydrochloride Arasto\u2019s code: AMI CAS Registry Number: [549-18-8] Drug Substance General Information (ICH 3.2.S.1) \u00a01.2. Structure (ICH 3.2.S.1.2) Empirical […]<\/p>\n","protected":false},"featured_media":7137,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[72],"product_tag":[],"class_list":["post-6116","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-72"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6116","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=6116"}],"version-history":[{"count":1,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6116\/revisions"}],"predecessor-version":[{"id":7139,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6116\/revisions\/7139"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7137"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6116"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6116"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6116"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}