BRIEFING

 Cinacalcet Hydrochloride. Because there is no existing USP monograph for this drug substance, a new monograph based on validated methods of analysis is being proposed. Based on comments received, the proposal in PF 42(4) has been canceled and is being replaced with a new proposal.

1. The liquid chromatographic procedure in the Assay and Organic Impurities, Procedure 1 was validated using the Discovery RP-Amide C16 brand of column with L60 packing. The typical retention time for cinacalcet is about 18 min.

2. The liquid chromatographic procedure in Organic Impurities, Procedure 2 was validated using the Hypersil Gold brand of column with L1 packing. The typical retention time for cinacalcet is about 19 min.

3. The liquid chromatographic procedure in Organic Impurities, Procedure 3 was validated using the YMC Hydrosphere C18 brand of column with L1 packing. The typical retention time for cinacalcet is about 16 min.

4. The liquid chromatographic procedure in Organic Impurities, Procedure 4 was validated using the ACQUITY UPLC HSS C18 brand of column with L1 packing. The typical retention time for cinacalcet is about 17 min.

5. The liquid chromatographic procedure in the Limit of Cinacalcet Related Compound A test was validated using the Gemini NX-C18 brand of column with L1 packing. The typical retention time for cinacalcet related compound A is about 16 min.

6. The liquid chromatographic procedure in the Enantiomeric and Isomeric Purity test was validated using the Chiralpak AD-H brand of column with L51 packing. The typical retention time for cinacalcet is about 7 min.

 Manufacturers are encouraged to share any information pertaining to the mutagenicity of cinacalcet related compound A.

 Description and solubility information: White to off-white crystalline powder. Soluble in methanol and in ethanol; slightly soluble in water.

 (SM3: S. Singireddy)

 Case ID—SUB-283, SUB-972, SUB-2285, SUB-2286