(USP 44)

  1. Drug Substance General Information (ICH 3.2.S.1)

1.1. Nomenclature (ICH 3.2.S.1.1)

International non-Proprietary Name: Loratadine (Brand Name: Claritine, Clarityn, Lisino)

Compendial Name: Loratadine

Chemical Name: Ethyl 4-(8-Chloro-5, 6-dihydro-11H-benzo [5, 6] cyclohepta [1, 2-b] pyridin-11- ylidene)-1-piperidinecarboxylate

Arasto’s code: LOR

CAS Registry Number: [79794-75-5]


  1. Drug Substance General Information (ICH 3.2.S.1)

 1.2. Structure (ICH 3.2.S.1.2)

Empirical Formula: C22H23ClN2O2

Molecular Weight: 382.88 g/mol

  1. Drug Substance General Information (ICH 3.2.S.1)

  1.3. General Properties (ICH 3.2.S.1.3)

Loratadine is a white to off-white crystalline substance. It is administered orally for the treatment of symptoms of seasonal allergic rhinitis and for the treatment of chronicidiopathicurticaria.  It is practically insoluble in water and slightly soluble in 0.1 M HCl (4.1 mg/ml at 25°C due to salt formation at the pyridine moiety), but highly soluble in most polar organic solvent except saturated hydrocarbons.  It has a pKa of 5 (http://druginfosys.com/Drug.aspx?drugCode=428 &drugName=&type=0) and a log P of 3.65 (http://pharmacycode.com/Loratadine.html). Loratadine is relatively stable to acid and base (see Stability Studies). Oral LD50 of Loratadine has been reported to be orally> 2000 mg/kg in the rat (http://web.ncifcrf.gov/rtp/LASP/intra/forms/msds/msds_Loratadine).

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).  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.

According to ICH Q7, 11.1 there are 3 types of standards.  This is summarized in the following chart and discussed in detail below.


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 ε or ג/max, IR major absorptions, 1HNMR d (ppm), 13CNMR d (ppm) or HPLC retention time with values reported in the chemical literature for these compounds.

  1. Primary and Secondary Reference Standard (ICH 3.2.S.5)

5.1. Active Pharmaceutical Ingredient

Primary Reference Standard for Loratadine 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 Loratadine.

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, must 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. To this end, the Secondary Reference Standards of the API Loratadine has undergone extensive characterization (UV, IR, 1 H NMR, 13C NMR, Mass Spec) to assure its structure, assay and purity (HPLC and/or titration) and specification (comparison of its HPLC retention time and UV ג/max with USP Primary Reference Standard.

The Secondary Reference Standard for Loratadine was produced from a released batch of Loratadine 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.


Product: LoratadineCAS No: 79794-75-5Spec. No.: APC-QC-SPEC-383-00
Issue Date: Apr, 2023Valid up to: Apr, 2024Reference: USP44


DescriptionWhite to off-white powder.
SolubilityFreely soluble in acetone, in chloroform, in methanol, and in toluene, insoluble in water.
IdentificationA: Infrared Spectroscopy

B: The retention time of the major peak of the sample solution corresponds to that of the Standard Solution, as obtained in the Assay.

Loss on dryingNMT 0.5%
Residue on ignitionNMT 0.1%
Residual SolventsMethanol: NMT 3000 ppm (Class II)

Toluene: NMT 890 ppm (Class II)

Organic Impurities ;Procedure 2 (HPLC)Loratadine related compound A: NMT 0.1%

Loratadine related compound B: NMT 0.1%

Loratadine related compound C: NMT 0.1%

Hydroxyl deacyl analog: NMT 0.1%

Dichlorobenzocycloheptapyridinone: NMT 0.1%

Hydroxyloratadine: NMT 0.1%

4-Chloroloratadine: NMT 0.1%

Any individual unknown impurity: NMT 0.10%

Total impurities: NMT. 0.3%

Assay (HPLC)98.5% to 101.0% (on the dried basis)
Prepared by: M. Shahbazi, B.Sc.Chem.Checked by: A. Forghani, B.Sc.Chem.
Approved by: F. Javadizadeh, M.Sc.Chem.
Storage: Preserve in well-closed containers, and store between 2° and 30°.