Indirect reversed‐phase high‐performance liquid chromatographic and direct thin‐layer chromatographic enantioresolution of (R,S)‐Cinacalcet

Abstract

Enantioresolution of the calcimimetic drug (R,S)-Cinacalcet was achieved using both indirect and direct approaches. Six chiral variants of Marfey's reagent having L-Ala-NH(2), L-Phe-NH(2), L-Val-NH(2), L-Leu-NH(2), L-Met-NH(2) and D-Phg-NH(2) as chiral auxiliaries were used as derivatizing reagents under microwave irradiation. Derivatization conditions were optimized. Reversed-phase high-performance liquid chromatography was successful using binary mixtures of aqueous trifluoroacetic acid and acetonitrile for separation of diastereomeric pairs with detection at 340 nm. Thin silica gel layers impregnated with optically pure L-histidine and L-arginine were used for direct resolution of enantiomers. The limit of detection was found to be 60 pmol in HPLC while in TLC it was found to be in the range of 0.26-0.28 µg for each enantiomers.

Enantioresolution of Amino Acids: A Decade’s Perspective, Prospects and Challenges

“…10) introduced by Bhushan and Tanwar showed successful separation of diastereomers of dl-PenA on RP-HPLC with the advantage of one step room temperature derivatization and low detection limits (0.5-2.5 pmol range) [178]. (S)-Naproxen-benzotriazole as a new CDR was introduced by Bhushan et al to prepare diastereomers of PenA, Cys and homocysteine under microwave irradiation [179], and 18 proteinogenic amino acids by microwave irradiation and vortexing [180] followed by their separation on RP-HPLC with UV detection at 231 nm. In conclusion, they highlighted that the large, highly conjugated naphthyl ring of CDR attached to the chiral center offers high UV absorbance and gives detection at very low concentration (LOD 0.1-1.2 pmol range), and the hydrophobic property of the naphthyl ring facilitates enantioresolution.…”

Determination of Cinacalcet Hydrochloride by Capillary Electrophoresis With Photodiode Array Detection

“…[12] This high enables the determination of trace amounts of cinacalcet hydrochloride in either its bulk powder or tablets. …”

“…These methods include spectrophotometric, [10] fluorimetric, [11] and liquid chromatographic techniques. [12][13][14][15] No stability-indicating assay was described for cinacalcet hydrochloride.…”

LC‐MS/MS determination of cinacalcet enantiomers in rat plasma on Chirobiotic V column in polar ionic mode: application to a pharmacokinetic study

“…Ravinder et al (2009) reported enantiomeric separation of CIN on Chiralpak-IA column in normal phase mode. Bhushan and Dubey (2011) developed a derivatization method with chiral reagents for separation of CIN enantiomers. However, these methods are not applicable to clinical pharmacokinetics and, in the literature, so far no method has been reported in polar ionic mode for chiral separation of CIN enantiomers on columns packed with vancomycin as a chiral stationary phase.…”