Liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of Vildagliptin in rat plasma

Sakthimanigandan, Kalaimani; Ganesh, Mani; Kanthikiran, V. V.S.; Sivakumar, T; Jang, Hee-Jin

doi:10.1556/achrom.27.2015.2.7

Cited by 13 publications

(6 citation statements)

References 12 publications

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“…The chemical structure of vildagliptin is depicted in Figure 1. A few HPLC and LC/MS methods were described in the literature for determination of vildagliptin in one-component formulations [4,5] or plasma [6,7]. Besides, HPLC and LC/MS methods were developed for determination of vildagliptin in the presence of other drugs in two-or three-component mixtures [8][9][10][11] and biological fluids [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Insight into Chemical Stability of Important Antidiabetic Drug Vildagliptin Using Chromatography (LC-UV and UHPLC-DAD-MS) and Spectroscopy (Mid-IR and NIR with PCA)

et al. 2021

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During forced degradation, the intrinsic stability of active pharmaceutical ingredients (APIs) could be determined and possible impurities that would occur during the shelf life of the drug substance or the drug product could be estimated. Vildagliptin belongs to relatively new oral antidiabetic drugs named gliptins, inhibiting dipeptidyl peptidase 4 (DPP-4) and prolonging the activities of the endogenous incretin hormones. At the same time, some gliptins were shown as prone to degradation under specific pH and temperature conditions, as well as in the presence of some reactive excipients. Thus, forced degradation of vildagliptin was performed at high temperature in extreme pH and oxidative conditions. Then, selective LC-UV was used for quantitative determination of non-degraded vildagliptin in the presence of its degradation products and for degradation kinetics. Finally, identification of degradation products of vildagliptin was performed using an UHPLC-DAD-MS with positive ESI. Stability of vildagliptin was also examined in the presence of pharmaceutical excipients, using mid-IR and NIR with principal component analysis (PCA). At 70 °C almost complete disintegration of vildagliptin occurred in acidic, basic, and oxidative media. What is more, high degradation of vildagliptin following the pseudo first-order kinetics was observed at room temperature with calculated k values 4.76 × 10−4 s−1, 3.11 × 10−4 s−1, and 1.73 × 10−4 s−1 for oxidative, basic and acidic conditions, respectively. Next, new degradation products of vildagliptin were detected using UHPLC-DAD-MS and their molecular structures were proposed. Three degradants were formed under basic and acidic conditions, and were identified as [(3-hydroxytricyclo- [3.3.1.13,7]decan-1-yl)amino]acetic acid, 1-{[(3-hydroxytricyclo[3.3.1.13,7]decan-1-yl)amino]acetyl}-pyrrolidine-2-carboxylic acid and its O-methyl ester. The fourth degradant was formed in basic, acidic, and oxidative conditions, and was identified as 1-{[(3-hydroxytricyclo[3.3.1.13,7]-decan-1-yl)amino]acetyl}pyrrolidine-2-carboxamide. When stability of vildagliptin was examined in the presence of four excipients under high temperature and humidity, a visible impact of lactose, mannitol, magnesium stearate, and polyvinylpirrolidone was observed, affecting-NH- and CO groups of the drug. The obtained results (kinetic parameters, interactions with excipients) may serve pharmaceutical industry to prevent chemical changes in final pharmaceutical products containing vildagliptin. Other results (e.g., identification of new degradation products) may serve as a starting point for qualifying new degradants of vildagliptin as it is related to substances in pharmacopoeias.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Insight into Chemical Stability of Important Antidiabetic Drug Vildagliptin Using Chromatography (LC-UV and UHPLC-DAD-MS) and Spectroscopy (Mid-IR and NIR with PCA)

et al. 2021

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“…Recently, Sakthimanigandan et al (2015) published a method for vildagliptin that employed LLE and the selection of ethyl acetate as the LLE solvent was made after checking other commonly solvents used such as TBME, dichloromethane and diethyl ether. While the positive ionization mode worked well, further optimization of the mobile phase with ammonium acetate buffer and the pH maintenance at 3.4 enabled the achievement of an improved signal for quantitation (Sakthimanigandan et al, 2015).…”

Section: Bioanalysis Of Other Dpp4 Inhibitorsmentioning

confidence: 99%

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

Suresh

Srinivas²,

Mullangi

2016

Biomedical Chromatography

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Inhibition of dipeptidyl peptidase-4 (DPP4) is an emerging therapeutic approach for treating type 2 diabetes and has revolutionized the concept of diabetes management. Sitagliptin is the first approved orally active, potent, selective and nonpeptidomimetic DPP4 inhibitor. Incidence of hypoglycemia and weight gain is negligible with sitagliptin treatment. It is used as monotherapy or in combination with other anti-diabetic drugs to treat type 2 diabetes. There are numerous bioanalytical methods published for the analysis of sitagliptin in preclinical and clinical samples. This review focuses on the various HPLC and LC-MS/MS methods that have been used to analyze sitagliptin in various biological matrices. A small section is devoted to the bioanalysis of other DPP4 inhibitors such as vildagliptin, saxagliptin and linagliptin. This review provides key information in a concise manner regarding sample processing options, chromatographic/detection conditions and validation parameters of the chosen methods for sitagliptin and other DPP4 inhibitors.

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“…It is based on using the higher derivative of absorbance with the wavelength of parent zero-order spectra. A detailed review of the literature was studied for vildagliptin in single and combination forms such as spectrophotometric (Vaishali et al, 2021;Samer et al, 2019), HPLC (Abu et al, 2018;Jayaprakash and Natesan, 2017), LC/MS/MS (Sakthimanigandan et al, 2015) GC-MS (Uçaktürk, 2015) Capillary electrophoresis (Mahesh et al, 2017) and HPTLC (Patil et al, 2020). Derivative spectroscopy is an economi-cal method with minimal reagents and development period when compared with other analytical techniques.…”

Section: Introductionmentioning

confidence: 99%

A New Second-Derivative Spectrophotometric Method for the Determination of Vildagliptin in Pharmaceutical dosage form

Subhadip

et al. 2021

ijrps

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An accurate derivative spectrophotometric method was developed and validated for the determination of dipeptidyl peptidase inhibitor vildagliptin in the pharmaceutical dosage form. The second derivative of the UV spectra has enabled the estimation of vildagliptin absorbance at 217 nm without any interferences. Linearity, precision, accuracy, detection (LOD), and quantification (LOQ) limits were established for method validation. Calibration curve was linear in the range of 10-60 µg/mL with a regression coefficient of 0.998. The method was validated as per the International Conference on Harmonization (ICH Q2 (R1)). The limit of detection and the limit of quantification were found to be 2.06 µg/mL and 6.25 µg/mL, respectively. Intra and interday precision data illustrated that the method has acceptable reproducibility as the percentage relative standard deviation (RSD) was less than 2 %, which indicates the precision of the method. The recovery was 98.39 % by the standard addition method. The percentage assay of vildagliptin was 98.06 % which showed good applicability. The following results indicate that the procedure is accurate, precise, and reproducible while being simple and less time-consuming. The method was demonstrated to be adequate for routine analysis in quality control.

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Liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of Vildagliptin in rat plasma

Cited by 13 publications

References 12 publications

Comprehensive Insight into Chemical Stability of Important Antidiabetic Drug Vildagliptin Using Chromatography (LC-UV and UHPLC-DAD-MS) and Spectroscopy (Mid-IR and NIR with PCA)

Comprehensive Insight into Chemical Stability of Important Antidiabetic Drug Vildagliptin Using Chromatography (LC-UV and UHPLC-DAD-MS) and Spectroscopy (Mid-IR and NIR with PCA)

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

A New Second-Derivative Spectrophotometric Method for the Determination of Vildagliptin in Pharmaceutical dosage form

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