Abstract
The combination between peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists and dipeptidyl peptidase-IV (DPP-IV) inhibitors is proven to be a more effective management of type-II diabetes mellitus (T2DM), compared to either each as single therapy. One of the novelist promising combination is linagliptin (LIN) and pioglitazone HCl (PIO) within clinical trials phase-III. Three simple, precise, accurate, reliable, and earth-friendly spectrophotometric techniques were defined and validated for resolving this novel pharmaceutical combination within laboratory synthetic mixtures and bulk form without the need of previous separation. Method-I was first-derivative (D1) spectrophotometry based on estimating LIN at 247.80 nm absorbance (PIO's zero-crossing point) and PIO at 258.40 nm absorbance (LIN's zero-crossing point) exhibiting mean percentage recoveries of 100.55% and 99.40%, respectively. Method-II was area under curve (AUC) technique involving area measurements at two designated wavelength ranges; 292-305 nm and 265-279 nm for respective LIN and PIO determination and with respective mean percentage recoveries 99.65% and 99.67%. Method-III was isosbestic point spectrophotometry where collective concentrations of both analytes were estimated at isosbestic point. 273.05 nm. Concerning PIO, the concentrations were furnished through simple deduction of LIN concentration, previously determined by AUC technique, and a mean % recovery of 99.88 % was obtained. All three proposed techniques were linear over concentration range 6-30 μg/mL and 5-50 μg/mL for LIN and PIO, respectively. Moreover, such techniques were validated as through the laboratory-prepared mixtures as refer to the International Council for Harmonization (ICH) guidelines.
Highlights
IntroductionLinagliptin (LIN), chemically identified as (R)-7but-2-ynyl-8-(3-amino piperidinyl)-1-(4-methylquinazolin-2-ylmethyl)-3-methyl-3,7-dihydropurine -2,6-dione (Fig. 1a), exhibits dipeptidyl peptidase-4 (DPP-4) inhibition activity and a distinct xanthinebased scaffold
Aref et al Linagliptin (LIN), chemically identified as (R)-7but-2-ynyl-8-(3-amino piperidinyl)-1-(4-methylquinazolin-2-ylmethyl)-3-methyl-3,7-dihydropurine -2,6-dione (Fig. 1a), exhibits dipeptidyl peptidase-4 (DPP-4) inhibition activity and a distinct xanthinebased scaffold. Blockage of such enzyme prevents the destruction of incretin hormones: gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) triggering post-prandial insulin secretion and decrease that of glucagon for further blood glucose level reduction (Del Prato et al 2011)
Standard calibration graphs were constructed through plotting the analyte concentrations against their corresponding area under curve (AUC) of zero-order spectra within 292-305 nm and 265-279 nm wavelength ranges for LIN and Pioglitazone HCl (PIO), respectively
Summary
Linagliptin (LIN), chemically identified as (R)-7but-2-ynyl-8-(3-amino piperidinyl)-1-(4-methylquinazolin-2-ylmethyl)-3-methyl-3,7-dihydropurine -2,6-dione (Fig. 1a), exhibits dipeptidyl peptidase-4 (DPP-4) inhibition activity and a distinct xanthinebased scaffold. Pioglitazone HCl (PIO), chemically entitled 5-(p-[β-(5-ethylpyridin-2yl) ethoxy] benzyl)-1,3thiazolidine-2,4-dione monohydrochloride (Fig. 1b), is a glitazone drug class member exerting its pharmacological action mainly via enhancing insulin sensitivity and promoting blood glucose uptake Such hypoglycemic action is primarily via selective interaction with the peroxisome proliferator-activated receptor-gamma (PPAR-γ) controlling the glucose and lipid metabolism within muscles, liver, and adipose tissues (Aronoff et al 2000). The novelist promising combination between LIN and PIO is currently undergoing clinical trials, phase-III study (ClinicalTrials.gov identifier #: NCT01183013) (Gomis et al 2011, Nauck et al 2016) The latter pharmaceutical combination was well tolerated and furnished clinically significant improvements within the euglycemic control most likely related to the complementary mechanistic aspects of both drugs. Zero order absorption spectra were recorded against 0.1N hydrochloric acid as negative control sample over 200-400 nm wavelength range
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