Enantioselective Box Behenken Optimized HPLC-DAD Method for the Simultaneous Estimation of Alogliptin Enantiomorphs in Pharmaceutical For mulations and their Pharmacokinetic Study in Rat Plasma

Abstract

Purpose: A stereoselective high performance liquid chromatographic analytical method withphotodiode array detector was developed and validated as per the International Conferenceon Harmonization (ICH) guidelines for the determination of alogliptin (ALO) enantiomers informulations and rat plasma.Methods: Enantiomeric separation was performed on a Phenomenex Lux Cellulose-2 chiralcolumn. Box-Behnken design was used to identify the optimum conditions of the threeindependent variables for the desired output responses.Results: The HPLC peaks of ALO enantiomers and the internal standard pioglitazone wereachieved before 8 min with a resolution of 0.77 min between R and S enantiomer and resolutionof more than 2.0 between each enantiomer and pioglitazone (internal) with more than 95%recovery. The linearity range and the limit of quantification of both the enantiomers in rat plasmawere 10-70 ng mL-1 and 1.2 ng mL-1 respectively.Conclusion: The developed method after validation was successfully applied for estimation ofALO enantiomers in formulations. Single oral dose of 25 mg of the ALO racemate tablets wereadministered to a group of 6 healthy rats for a comparative pharmacokinetic study of both theenantiomers.

An overview of chiral separations of pharmaceutically active substances by HPLC (2018–2020)

“…The Lux AMP column, primarily intended for the analysis of synthetic chiral drugs such as amphetamine and 3,4-(methylenedioxy)methamphetamine, was used for enantioseparation of new psychoactive drugs, and 88 of 95 drugs tested were successfully enantioseparated at pH 11.3 without stationary phase damage [ 50 ]. A Lux Cellulose-2 was applied for the analysis of alogliptin, a selective inhibitor of the enzyme dipeptidyl peptidase-4 (used to treat diabetes) [ 51 , 52 ]. Both this column and Lux Cellulose-1 column were shown to be useful for enantioseparation of selective heme oxygenase-1 inhibitors [ 53 ].…”

Hantzsch condensation reaction as a spectrofluorometric method for determination of alogliptin, an antidiabetic drug, in pure form, tablet form, and human and rat plasma

“…[ 1–3 ] ALO’s scientific name is 2‐[[6‐[(3R)‐3‐aminopiperidin‐1‐yl]‐3‐methyl‐2,4‐dioxopyrimidin‐1‐yl][2]methyl]benzonitrile (Figure 1) with empirical formula C 18 H 21 N 5 O 2. [ 4 ] Some attempts have been made to estimate ALO either alone or in conjunction with other medications, including using capillary electrophoresis, [ 5 ] conductometry, [ 6 ] high performance liquid chromatography (HPLC), [ 7–30 ] spectrophotometry, [ 7,17,31–36 ] spectrofluorometry, [ 37,38 ] and thin‐layer chromatography [ 27,39–41 ] methods. The use of costly reagents (e.g.…”

Spectrofluorometric determination of alogliptin an antidiabetic drug in pure and tablet form using fluorescamine, a fluorogenic agent: application to content uniformity test

“…[ 3 ] The systematic name of ALO is 2‐[[6‐[(3R)‐3‐aminopiperidin‐1‐yl]‐3‐methyl‐2,4‐dioxopyrimidin‐1‐yl]methyl]benzonitrile (Figure 1) with empirical formula C 18 H 21 N 5 O 2. [ 2 ] There have been some efforts to determine ALO either alone or in combination with other drugs including using spectrophotometry [ 4–12 ] , spectrofluorimetry [ 13 ] , thin layer chromatography [ 14–18 ] , high performance liquid chromatography (HPLC) [ 7,19–41 ] , capillary electrophoresis [ 42 ] , and conductometry [ 43 ] methods.…”