A new stability indicating reverse phase high performance liquid chromatography method for the determination of enantiomeric purity of a DPP‐4 inhibitor drug linagliptin

Abstract

A simple, sensitive, and stability indicating isocratic reverse phase high performance liquid chromatography method has been developed, optimized and validated for the separation and quantification of S-enantiomer in linagliptin (R-enantiomer) drug substance. Enantiomeric separation was achieved on a Cellulose tris(4-chloro-3-methylphenylcarbamate) stationary phase. Mobile phase consists of aqueous diammonium hydrogen phosphate buffer and acetonitrile in the ratio of 35:65 v/v. Isocratic elution was performed at a flow rate of 1.0 mL/min, the column oven temperature was set at 40°C and detection was at 226 nm. The resolution between R and S enantiomers is found to be more than 4.0. The impact of mobile phase composition, pH of buffer and temperature on the resolution has been studied. The detector response is found to be linear over the concentration range of 0.17-1.7 g/mL. LOD and LOQ levels of S-enantiomer are found to be 0.057 and 0.172 g/mL respectively. The recovery of S-enantiomer is 99.8% w/w. The proposed method is validated for specificity, precision, linearity, accuracy and robustness.

Application of online liquid chromatography/quadrupole time‐of‐flight electrospray ionization tandem mass spectrometry for structural characterization of linagliptin degradation products and related impurities

“…In addition, some bioanalytical methods were reported for LIN ‐ related to its pharmacology, kinetics and drug interactions 13–16 . There have been a few studies on the stability of LIN alone and in combination with other antidiabetic drugs in formulations using HPLC 17–19 and two reports on the impurity analysis of LIN 20,21 . However, there is no information available on the degradation behavior of LIN.…”

A capillary electrophoresis method for the determination of the linagliptin enantiomeric impurity

“…Compared to the published HPLC methods [4][5][6][7], the proposed CE method was demonstrated to be an equivalently precise, sensitive, and robust method with reduced running time, thus making it a more convenient routine analysis method. The elution order of the S-enantiomer peak before the large peak of Lina suggested that the CE method is reliable because the small impurity peak is not likely to overlap with the Lina peak.…”

“…Recent chiral drug analyses have mostly been based on HPLC and CE methods. Several chiral HPLC methods have recently been proposed using cellulose-and amylose-based chiral stationary phases for the quantification of S-Lina [4][5][6][7]. The published HPLC methods efficiently resolved Lina enantiomers as well as determined the S-enantiomer content in the bulk drug of Lina.…”

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.…”