Compatible validated spectrofluorimetric and spectrophotometric methods for determination of vildagliptin and saxagliptin by factorial design experimentsby Omar Abdel-Aziz, Miriam F. Ayad, Mariam M. Tadros

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

About

Year
2015
DOI
10.1016/j.saa.2014.12.102
Subject
Instrumentation / Analytical Chemistry / Atomic and Molecular Physics, and Optics / Spectroscopy

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Accepted Manuscript

Compatible validated spectrofluorimetric and spectrophotometric methods for determination of vildagliptin and saxagliptin by factorial design experiments

Omar Abdel-Aziz, Miriam F. Ayad, Mariam M. Tadros

PII: S1386-1425(14)01890-3

DOI: http://dx.doi.org/10.1016/j.saa.2014.12.102

Reference: SAA 13152

To appear in: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Received Date: 9 October 2014

Revised Date: 8 December 2014

Accepted Date: 28 December 2014

Please cite this article as: O. Abdel-Aziz, M.F. Ayad, M.M. Tadros, Compatible validated spectrofluorimetric and spectrophotometric methods for determination of vildagliptin and saxagliptin by factorial design experiments,

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2015), doi: http://dx.doi.org/10.1016/j.saa. 2014.12.102

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Compatible validated spectrofluorimetric and spectrophotometric methods for determination of vildagliptin and saxagliptin by factorial design experiments

Omar Abdel-Aziz, Miriam F. Ayad, Mariam M. Tadros*

Analytical Chemistry Department, Faculty of Pharmacy, Ain Shams University,

Abbassia, Cairo 11566, Egypt.

The authors certify that this article is original and unpublished and is not being considered for publication elsewhere. ________________________________________________________________________ * Corresponding author

Tel: +201223345260; fax: +20224051107

E-mail address: mariam.tadros@hotmail.com 2

Abstract:

Simple, selective and reproducible spectrofluorimetric and spectrophotometric methods have been developed for the determination of vildagliptin and saxagliptin in bulk and their pharmaceutical dosage forms. The first proposed spectrofluorimetric method is based on the dansylation reaction of the amino group of vildagliptin with dansyl chloride to form a highly fluorescent product. The formed product was measured spectrofluorimetrically at 455 nm after excitation at 345 nm. Beer’s law was obeyed in a concentration range of 100-600 µgml-1. The second proposed spectrophotometric method is based on the charge transfer complex of saxagliptin with tetrachloro-1,4-benzoquinone (p-chloranil). The formed charge transfer complex was measured spectrophotometrically at 530 nm. Beer’s law was obeyed in a concentration range of 100-850 µgml-1. The third proposed spectrophotometric method is based on the condensation reaction of the primary amino group of saxagliptin with formaldehyde and acetyl acetone to form a yellow colored product known as hantzsch reaction, measured at 342.5 nm. Beer’s law was obeyed in a concentration range of 50-300 µgml-1. All the variables were studied to optimize the reactions' conditions using factorial design. The developed methods were validated and proved to be specific and accurate for quality control of vildagliptin and saxagliptin in their pharmaceutical dosage forms.

Keywords: Vildagliptin; Saxagliptin; Experimental design; Dansylation; Charge transfer reaction; Hantzsch reaction.

Introduction:

Vildagliptin (VLG), S-1-[N-(3-hydroxy-1-adamantyl) glycyl] pyrrolidine-2carbonitrile (Fig.1a) and Saxagliptin (SXG), (1S, 3S, 5S) ‐2‐ [(2S) ‐2‐amino‐2‐(3‐hydroxy‐1‐adamantyl) acetyl] ‐2‐azabicyclo [3.1.0] hexane‐3‐carbonitrile (Fig.1b) are novel oral hypoglycemic drugs of the dipeptidyl peptidase 4-inhibitor class (DPP‐4) [1-2]. DPP-4 inhibitors represent a new therapeutic approach for treatment of type-II diabetes; that functions to stimulate glucose-dependent insulin release and reduce glucagon’s levels. This is done through inhibition of the inactivation of incretins, particularly glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thereby improving glycemic control [3-5].

Literature review showed many methods for determination of VLG; based on the charge transfer complexes of VLG with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone 3 (DDQ), 7,7,8,8-tetracyanoquinodimethane (TCNQ) and tetrachloro-1,4-benzoquinone (Pchloranil) [6]. Also; literature survey reveals that many chromatographic methods have been developed [7-13]. In addition; SXG has been estimated by LC‐MS/MS [14], HPLC methods [15-19] and by spectrophotometric method, in which SXG was estimated at 208 nm in methanol [20]. Another spectrophotometric method based on charge transfer reaction using DDQ and TCNQ was reported [21].

The aim of the first method is to present new spectrofluorimetric method based on the dansylation reaction for determination of VLG in bulk and in pharmaceutical dosage form. Furthermore, the established method should be rapid to be applied for routine quality control analysis of VLG in pharmaceutical dosage form.

Spectrofluorimetry has long been applied in the field of pharmaceutical analysis of many drugs [22-24]. A necessary condition for a compound to fluoresce is that it absorbs light in the UV or visible region of the spectrum or reacts with a reagent to give a fluorescent product. Accordingly, A certain group in the compound as the primary amine for example react with the reagent to obtain a highly fluorescent product [22-24]. Dansyl chloride is a useful derivatizing agent for primary amines, secondary amines, imidazoles and phenols. Several pharmaceutical compounds have been determined through this approach [25–31].

The aim of the second and third methods is to present new spectrophotometric methods based on a charge transfer reaction and Hantzsch reaction for the determination of SXG in bulk and pharmaceutical dosage forms.