(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: Docetaxel (Brand Name: Taxotere, Sanofi Oncology (Sanofi), USA

Compendial name: Docetaxel

Chemical name: 1,7β,10β-trihydroxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate}

Arasto’s code: DOC

CAS Registry Number: [114977-28-5]

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

1.2 Structure (ICH 3.2.S.1.2)


Empirical formula: C43H53NO14. 3H2O

Molecular Weight: 861.90 g/mol


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

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

Docetaxel is a white crystalline substance. It is practically insoluble in water and soluble in polar organic.  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 (. Its log P is 4.26 ( _assessment_report /human/001107/WC500073418.pdf).  Docetaxel is not stable in acid or base (see Stability Studies and EP 1978953A1). LD50 of docetaxel has been reported ( > 2000 mg/kg oral  rat; 138 mg/kg IV mouse, safety data/ PZ00906 .pdf).

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) , 13 CNMR 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 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.

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 docetaxel has undergone extensive characterization (UV, IR, 1 H NMR, 13C 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 ג /max with USP Primary Reference Standard.

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.


Product: Docetaxel. 3H2OCAS No.: 148408-66-6Spec. No.: APC-QC-SPEC-378-00
Issue Date: Apr, 2023Valid up to: Apr, 2024Reference: USP44


DescriptionWhite or almost white, crystalline powder.
SolubilityFreely Soluble in acetone; soluble in methanol; practically 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.

Optical Rotation-39˚ to -41˚ calculated on the anhydrous and solvent free basis.
Water determination5.0% to 7.0%.
Residue on ignitionNMT 0.1%
Residual SolventsAcetone: NMT 5000 ppm (Class III)

Ethanol: NMT 5000 ppm (Class III)

Ethyl acetate: NMT 5000 ppm (Class III)

Dichloromethane: NMT 600 ppm (Class II)

Methanol: NMT 3000 ppm (Class II)

Toluene: NMT 890 ppm (Class II)

Chloroform: NMT 60ppm (Class II)

Heptane: NMT 5000 ppm (Class III)

Organic impurities (procedure 1)10-Deacetyl baccatin: NMT 0.15%

N-Formyl impurity: NMT 0.15%

2-Debenzoxyl 2-pentenoyl docetaxel: NMT 0.5%

6-Oxodocetaxel: NMT 0.3%

4-Epidocetaxel: NMT 0.3%

4-Epi-6-oxodocetaxel: NMT 0.2%

6-Dichloroethoxycarbonyl docetaxel: NMT 0.15%

Any unspecified impurity: NMT 0.10%

Total impurities: NMT 1.0%

AssayNLT 97.5% and NMT 102.0% (on the anhydrous and solvent-free basis)
Microbial limit test(MLT)

Total aerobic Microbial count

Total yeast and moulds count

Test of pathogen

1. E. Coli

2. P.aeruginosa

3. Salmonella species

4. S. aureus

Endotoxin Limit

NMT 100 CFU/g

NMT 10 CFU/g

Should be Absent

Should be Absent

Should be Absent

Should be Absent

NMT 0.4 EU/mg

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, light resistant containers, and storage at room temperature or between 2° C and 8° C.