Enantiomeric separation of sitagliptin by a validated chiral liquid chromatographic method

Abstract

An enantioselective reversed phase high performance liquid chromatographic method was developed and validated. The enantiomers of sitagliptin were resolved on a Chiralcel OD-RH (150 mm  4.6 mm, 5 mm) column using a mobile phase system containing 3 M potassium di-hydrogen phosphate buffer (pH 4.0)methanol-acetonitrile (60 : 30 : 10, v/v/v). The resolution between the enantiomers was not less than 3.0. The pH value of buffer solution in the mobile phase played a key role in enhancing chromatographic efficiency and resolution between the enantiomers. The developed method was validated according to ICH guidelines. The calibration curve was found to be linear over the concentration range of 30-300 ng mL À1 (r 2 ¼ 0.9996). The limit of detection and limit of quantification of the (S)-enantiomer were found to be 8 and 30 ng mL À1 , respectively, for 20 mL injection volume. The percentage recovery of the (S)-enantiomer ranged from 99.06 to 100.2 in bulk drug samples of sitagliptin. The sample solution and mobile phase were found to be stable at least for 48 h. The final optimized method was successfully applied to separate the (S)-enantiomer from sitagliptin and was proved to be reproducible, accurate and robust for the quantitative determination of the (S)-enantiomer in bulk drugs.

A concise review of the bioanalytical methods for the quantitation of sitagliptin, an important dipeptidyl peptidase‐4 (DPP4) inhibitor, utilized for the characterization of the drug

“…Under these conditions, the peak shapes of both S-and R-sitagliptin enantiomers appeared to be symmetrical and resolution factor was at least 4.0 (Reddy et al, 2013). Recently, Ramesh et al (2014) reported an enatioselective LC-MS/MS method for quantitative determination of undesired (S)-sitagliptin from sitagliptin in bulk drugs. Both the enantiomers' resolutions were ≥3.0 and this was achieved on Chiracel OD-RH column using an isocratic mobile phase (3 M potassium dihydrogen phosphate-MeOH-water, 60:30:10, v/v/v) within 10 min run time.…”

“…Among these columns only Chiralpak AD-RH and Chiralcel OJ-RH gave the required selectivity between sitagliptin and undesired impurity. Based on further optimization of mobile phase composition and baseline separation of the two peaks, Chiracel OD-RH was chosen for method validation purposes (Ramesh et al, 2014).…”

Surfing the vildagliptin tsunami

“…Enantiomers of drugs often differ in their pharmacological action. Other gliptins such as linagliptin,[ 10 ] alogliptin,[ 11 ] and sitagliptin[ 12 ] and teneligliptin also show chirality. However, with the exception of teneligliptin—all the other gliptins are manufactured by a single company.…”

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“…Sitagliptin analysis also has been reported with its degradation product and metformin using HPLC 8 , with its N-acetyl impurity, metformin and metformin related impurities using UPLC 9 . So far there are only two published direct enantiomeric separation methods using AD-H column 10 , an OD-RH column 11 and an indirect method 12 .…”