Teneligliptin Research Articles

An optimization through experimental design approach for simultaneous quantification of Remogliflozin and Teneligliptin by RP-UFLC

The combination of teneligliptin (TEN) with remogliflozin etabonate (REM) is the latest FDC approved for the treatment of type-2 diabetes. There is no QBD optimized UFLC method reported with short runtime for quantification of TEN and REM. Hence this research work aimed to find a new way to quantify a novel antidiabetic combination of TEN and REM using RP-UFLC technique with possible minimum run time, optimized with QBD. The method was executed using the Agilent Eclipse XDB C-18 column (150 x 4.6 mm; 5 μm), with the mobile phase comprising of buffer and acetonitrile (41:59) at a flow rate of 2.2 mL per minute and determination has been carried out at 230 nm. The retention time for TEN and REM was found at 0.770 and 1.465 minute correspondingly with runtime only 2 min. The method's effectiveness has been validated using ICH guideline for LOD, LOQ, linearity, precision, accuracy, robustness and forced degradation. In the proposed study, TEN and REM were successfully separated with very short run time of only 2 minutes. The results of validation for proposed UFLC method revealed the accuracy, specificity and forced degradation of the method. Furthermore, determination of TEN and REM from formulations showed the correctness of the method. The method is novel, easy to use, fast, precise and accurate and it can be used in QC laboratories for regular studies on API and dosages.

In silico modified UV spectrophotometric approaches to resolve overlapped spectra for quality control of rosuvastatin and teneligliptin formulation

Abstract A binary blend of rosuvastatin (ROS) and teneligliptin (TEN) used for the management of cardiovascular complications require a simple, analytical process for the quality assurance of this formulation. UV absorption spectra of ROS and TEN showed overlapping spectra. Hence, the overlapped spectra of ROS and TEN were separated by ratio difference, ratio first derivative; constant extraction coupled with exponentiation with division spectrum, and induced dual-wavelength methods. The proposed methods were authenticated by following the international council for harmonization criteria. A good linear relationship was demonstrated by all four methods, in 2–15 and 2–30 µg/mL for ROS and TEN, respectively. The high percentage retrieval of 98.96–100.22 and 98.72–99.73% for ROS and TEN, respectively, with small relative error, assured the correctness of the techniques. The validated techniques were employed for concurrent evaluation of ROS and TEN from binary formulation and laboratory-prepared mixture. The standard addition process verified the reliability of the projected procedures. The developed methods showed same accuracy and precision when compared to the HPLC methods along with safer solvent. Finally, the environmental sustainability of the presented UV spectroscopic procedures was found to be better than the reported HPLC method. Hence, eco-friendly, simple, and accurate mathematically processed UV spectroscopic procedures can be employed for simultaneous quantification of ROS and TEN for routine quality control study.

Teneligliptin Co-Infusion Alleviates Morphine Tolerance by Inhibition of Spinal Microglial Cell Activation in Streptozotocin-Induced Diabetic Rats.

Morphine (MOR) is a commonly prescribed drug for the treatment of moderate to severe diabetic neuropathic pain (DNP). However, long-term MOR treatment is limited by morphine analgesic tolerance (MAT). The activation of microglial cells and the release of glia-derived proinflammatory cytokines are known to play an important role in the development of MAT. In this study, we aimed to investigate the effects of the dipeptidyl peptidase-4 inhibitor (DPP-4i) teneligliptin (TEN) on MOR-induced microglial cell activation and MAT in DNP rats. DNP was induced in four groups of male Wistar rats through a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Sham rats were administered with the vehicle. Seven days after STZ injection, all rats were implanted with an intrathecal (i.t) catheter connected to a mini-osmotic pump, divided into five groups, and infused with the following combinations: sham + saline (1 µL/h, i.t), DNP + saline (1 µL/h, i.t), DNP + MOR (15 µg/h, i.t), DNP + TEN (2 µg/h, i.t), and DNP + MOR (15 µg/h, i.t) + TEN (2 µg/h, i.t) for 7 days at a rate of 1 μL/h. The MAT was confirmed through the measurement of mechanical paw withdrawal threshold and tail-flick tests. The mRNA expression of neuroprotective proteins nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in the dorsal horn was evaluated by quantitative PCR (qPCR). Microglial cell activation and mononucleate cell infiltration in the spinal cord dorsal horn were assessed by immunofluorescence assay (IFA) and Western blotting (WB). The results showed that co-infusion of TEN with MOR significantly attenuated MAT in DNP rats through the restoration of neuroprotective proteins Nrf2 and HO-1 and suppression of microglial cell activation in the dorsal horn. Though TEN at a dose of 2 μg has mild antinociceptive effects, it is highly effective in limiting MAT.

Simultaneous Gas Chromatographic Analysis of Isopropyl Alcohol, t-Butanol, 2-Bromo Propane, Toluene and Acetic Acid in Teneligliptin Drug

Teneligliptin (TNN), a true third-generation gliptin, has firmly established itself as an essential therapeutic molecule in the therapy of diabetes. The monitoring of isopropyl alcohol (ISO), t-butanol (BUT), 2-bromo propane (BRO), toluene (TOU) and acetic acid (ACE) in TNN is necessary to maintain TNN’s stability, bioavailability and solubility. We have established a “gas chromatography” approach for ISO, BUT, BRO, TOU and ACE determination in TNN sample. The analysis of ISO, BUT, BRO, TOU and ACE in TNN were performed deploying ZB-624 analysing column. The flame ionizing sensor was deployed. Linear response was ascertained for ISO, BUT, BRO, TOU and ACE over the concentration arrays 29.96 to 7512ppm, 25.83 to 759 ppm, 48.48 to 762ppm, 4.92 to 1362ppm and 222.41 to 7527ppm, respectively. Detection limits were 8.99ppm (ISO), 7.75ppm (BUT), 14.55ppm (BRO), 1.34ppm (TOU) and 67.47ppm (ACE). The “gas chromatography” approach validation set their precision, specificity, accuracy and robustness. Routine monitoring and proper analysis of ISO, BUT, BRO, TOU and ACE in TNN sample in quality management laboratories could be accomplished deploying “gas chromatography” approach.

Environmental sustainable mathematically processed UV spectroscopic methods for quality control analysis of remogliflozin and teneligliptin: Evaluation of greenness and whiteness

Environmental sustainable analytical methods were developed by mathematical modification of UV absorption spectra for quality control study of multicomponent formulations consisting of remogliflozin (REM) and teneligliptin (TEN), with good sensitivity and selectivity. Then analytes were quantified by measuring the peak amplitude of the first derivative spectra at zero crossing points at 230.2 nm and 213.8 nm for REG and TEN in the first derivative method. The second method involves the formation of ratio spectra and taking the absorption difference at two selected wavelengths of peak and trough of a spectrum. In the ratio first derivative method peak amplitudes were measured at 235.2 nm and 259.1 nm for simultaneous quantification of REM and TEN respectively. The fourth method was based on the measurement of the peak amplitude of zero-order spectra of analytes generated from the mixture spectrum by subtraction of a constant from the ratio spectrum followed by multiplication with divisor spectrum, Further, the proposed methods were validated systematically to confirm the linearity, precession, accuracy, sensitivity, and selectivity. Finally, validated UV spectroscopic methods were applied for simultaneous quantification of REM and TEN from formulation, and laboratory mixed solutions and statistically compared with the reported HPLC method. Further, recently developed AGREE, Hexagonal greenness and white analytical chemistry, a whiteness evaluation tools were applied to the proposed UV spectroscopic methods and found to be safer analytical methods, compared to the reported expensive, time-consuming and toxic HPLC method. Hence, proposed UV spectroscopic methods could be used for routine quality control of formulations containing REM and TEN.

Therapeutic Effect of Teneligliptin in Drug-Induced Nephrotoxicity: An In-Vitro Study.

BackgroundDrug-induced nephrotoxicity is an important side effect of many commonly used drugs. In this study, we planned to evaluate the effects of teneligliptin (TG), which is a dipeptidyl peptidase-4 (DPP-4) inhibitor, on cell healing by creating nephrotoxicity models in human renal proximal tubule cell and human embryonic kidney epithelial cells cell lines in-vitro with cisplatin, vancomycin, and gentamicin.MethodologyFirst, we determined the 50% inhibitory concentration doses of nephrotoxic drugs and the nephroprotective dose of TG. Then, we analyzed the difference in cell viability, apoptosis, and oxidative stress (reactive oxygen and nitrogen species (ROS/RNS) production) between TG-treated and untreated cells after nephrotoxicity occurred. Moreover, we evaluated the expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in cells.ResultsWe found that when cell lines were treated after toxicity was induced with TG, cell viability increased, apoptosis and ROS/RNS production were significantly decreased, and expressions of KIM-1 and NGAL were significantly reduced.ConclusionsThis study showed that TG has positive effects on the recovery of drug-induced nephrotoxicity in an in-vitro setting.

Development and Validation of Teneligliptin Stereoisomers by HPLC Using Cellulose Based Immobilized Polysaccharide Chiral Stationary Phase

Background: There is no single chiral method for the quantitation of teneligliptin stereoisomers by high performance liquid chromatography (HPLC). Hence, there is a need for the quantification of teneligliptin (TNGP) and its stereoisomers. Objective: The main aim of the research work is to develop a novel simple, selective, precise and accurate HPLC method for the separation of TNGP and its stereoisomers. Methods: Different screening trials were executed by changing the mobile phase compositions to normal phase and polar mode and also by utilizing the different immobilized polysaccharide chiral columns like CHIRALPAK IA, IC, ID, IE, IF and IG. All the stereoisomers were eluted with high resolution, on CHIRALPAK IC-3 (4.6×250 mm), 3 μm chiral stationary phase (CSP) with a flow rate of 0.7 mL/min. The chromatographic system was processed with isocratic mode comprising ethanol: acetonitrile: ethanolamine in the proportion of 90:10:0.1% v/v/v with a column oven temperature of 15°C and detection wavelength of 250 nm. Results: The limit of detection (LOD) and limit of quantification (LOQ) values of TNGP(API), R,S-isomer, S,R-isomer and R,R-isomer were found to be 0.036/0.11, 0.029/0.09, 0.038/0.011 and 0.020/0.06 μg/mL, respectively. The method was found to be precise, accurate and linear (R2 > 0.999). Conclusion: The developed method was successfully applied for the quantification of bulk drug without any interference with the extraneous components. Hence, the method can be utilized successfully in the pharmaceutical organizations for the separation and quantification of TNGP isomers.

Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain.

Neuropathic pain (NP), is a chronic pain resulting from nerve injury, with limited treatment options. Teneligliptin (TEN) is a dipeptidyl peptidase-4 inhibitor (DPP-4i) approved to treat type 2 diabetes. DPP-4is prevent the degradation of the incretin hormone glucagon-like peptide 1 (GLP-1) and prolong its circulation. Apart from glycemic control, GLP-1 is known to have antinociceptive and anti-inflammatory effects. Herein, we investigated the antinociceptive properties of TEN on acute pain, and partial sciatic nerve transection (PSNT)-induced NP in Wistar rats. Seven days post PSNT, allodynia and hyperalgesia were confirmed as NP, and intrathecal (i.t) catheters were implanted and connected to an osmotic pump for the vehicle (1 μL/h) or TEN (5 μg/1 μL/h) or TEN (5 μg) + GLP-1R antagonist Exendin-3 (9–39) amide (EXE) 0.1 μg/1 μL/h infusion. The tail-flick response, mechanical allodynia, and thermal hyperalgesia were measured for 7 more days. On day 14, the dorsal horn was harvested and used for Western blotting and immunofluorescence assays. The results showed that TEN had mild antinociceptive effects against acute pain but remarkable analgesic effects against NP. Furthermore, co-infusion of GLP-1R antagonist EXE with TEN partially reversed allodynia but not tail-flick latency. Immunofluorescence examination of the spinal cord revealed that TEN decreased the immunoreactivity of glial fibrillary acidic protein (GFAP). Taken together, our findings suggest that TEN is efficient in attenuation of PSNT-induced NP. Hence, the pleiotropic effects of TEN open a new avenue for NP management.

Isocratic RP-UHPLC method development and validation of stability-indicating for simultaneous determination of teneligliptin and metformin in fixed-dose combination

The pharmaceutical combination of Teneligliptin Hydrobromide hydrate (TEN) and Metformin Hydrochloride (MET) drugs is used in the treatment of type 2 diabetes mellitus. A new analytical method: QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) has been developed for the quantification of Teneligliptin (TEN) and Metformin (MET) in bulk and tablet dosage forms. The analysis was performed on Agilent symmetry analytical column Eclipse plus C18 (150 mm × 4.6 mm, 5 μm) ultra- performance liquid chromatography-Diode Array Detectors (UHPLC-DAD), while the detection was performed on 233 nm using Diode Array Detectors. Buffer and acetonitrile (65:35 v/v) were the mobile phase, run at a flow rate of 0.7 mL min−1 for isocratic elution. The buffer used in the mobile phase contained 50 mM potassium di-hydrogen phosphate, pH adjusted to 3.5±0.02 with orthophosphoric acid. The mean values of recovery were found to be 100.50% and 99.81%. The proposed method could be ideal for quantitative evaluation in pharmaceutical preparations of these drugs and also for their quality control in bulk manufacturing. Stress test covers: acid, base, peroxide, thermal and photolytic degradation; were conducted to show the specificity of the method and degradation.

Development and Validation of a Rapid and Sensitive Method for the Simultaneous Estimation of Gemigliptin and Teneligliptin in Bulk and Dosage Forms by Using Liquid Chromatography-tandem Mass Spectrometry

Background: A simple and sensitive ultra-performance liquid chromatography-mass spectrometry method was developed and validated to measure the concentrations of gemigliptin (GEM) and teneligliptin (TEN) using pioglitazone (PIO) as an internal standard. Methods: Chromatographic separation of two gliptins was achieved on a C-18 (100 mm X 2.1 mm, 2.7 μm) column using a mobile phase consisting of formic acid in water (0.1 % v/ v): acetonitrile in gradient elution. Electrospray ionization (ESI) source was operated in positive mode (ionization). Targeted MS-MS mode on a quadrupole time of flight (Q-TOF) mass spectrometer was used to quantify the drugs utilizing the mass transitions of 490.1 (m/z), 427.2 (m/z) and 357.1 (m/z) for GEM, TEN and PIO, respectively. Results: As per ICH Q2R1 guidelines, a detailed validation of the method was carried out and the standard curves were found to be linear between the concentration ranges of 509.8-1529.4 ng mL-1 and 510.6-1531.7 ng mL-1 for GEM and TEN, respectively. Precision and accuracy results were found to be within the acceptable limits. The mean recovery was found to be 98.8± 0.76 % (GEM) and 98.6 ±0.98 % (TEN), respectively. Conclusions: The optimized validated UPLC-QTOF (MS-MS) method offered the advantage of shorter analytical times and higher sensitivity and selectivity to the nanogram level.

Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis.

Hepatocellular carcinoma (HCC) is the strongest independent predictor of mortality in non-alcoholic steatohepatitis (NASH)-related cirrhosis. The effects and mechanisms of combination of sodium-dependent glucose cotransporter inhibitor and canagliflozin (CA) and dipeptidyl peptidase-4 inhibitor and teneligliptin (TE) on non-diabetic NASH progression were examined. CA and TE suppressed choline-deficient, L-amino acid-defined diet-induced hepatic fibrogenesis and carcinogenesis. CA alone or with TE significantly decreased proinflammatory cytokine expression. CA and TE significantly attenuated hepatic lipid peroxidation. In vitro studies showed that TE alone or with CA inhibited cell proliferation and TGF-β1 and α1 (I)-procollagen mRNA expression in Ac-HSCs. CA+TE inhibited liver fibrogenesis by attenuating hepatic lipid peroxidation and inflammation and by inhibiting Ac-HSC proliferation with concomitant attenuation of hepatic lipid peroxidation. Moreover, CA+TE suppressed in vivo angiogenesis and oxidative DNA damage. CA or CA+TE inhibited HCC cells and human umbilical vein endothelial cell (HUVEC) proliferation. CA+TE suppressed vascular endothelial growth factor expression and promoted increased E-cadherin expression in HUVECs. CA+TE potentially exerts synergistic effects on hepatocarcinogenesis prevention by suppressing HCC cell proliferation and angiogenesis and concomitantly reducing oxidative stress and by inhibiting angiogenesis with attenuation of oxidative stress. CA+TE showed chemopreventive effects on NASH progression compared with single agent in non-diabetic rat model of NASH, concurrent with Ac-HSC and HCC cell proliferation, angiogenesis oxidative stress, and inflammation. Both agents are widely, safely used in clinical practice; combined treatment may represent a potential strategy against NASH.

Effect of resveratrol on dipeptidyl peptidase-4 inhibitors pharmacokinetics: An in vitro and in vivo approach

Diabetes mellitus (DM) is a metabolic disorder with hyperglycemia being its hallmark symptom. The secondary symptom of DM is oxidative stress, which leads to the generation of free radicals. Diabetic nephropathy and neuropathy is the long-term effect of oxidative stress caused in DM, which leads to damage of kidneys and neurons respectively. Resveratrol (RES) is a phytochemical, found to be effective in the treatment of diabetic nephropathy and neuropathy. Due to its antioxidant property, it reduces the oxidative stress caused by DM. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used for the treatment of type 2 DM. In vitro and in vivo data depicted that the metabolism of alogliptin (ALO), saxagliptin (SAX) and sitagliptin (SIT) were decreased in presence of RES while metabolism of teneligliptin (TEN) was not affected in presence of RES. The results show that the alteration of the pharmacokinetics of ALO, SAX and SIT was due to inhibition of CYP P450 by RES. Thus, there was a significant pharmacokinetic interaction between RES-ALO, RES-SAX and RES-SIT. Hence, a dose reduction is required when RES therapy is taken in combination with ALO, SAX and SIT as there is an increase in drug exposure, which might lead to toxicity.

Dipeptidyl peptidase-4 plays a pathogenic role in BSA-induced kidney injury in diabetic mice

Diabetic kidney disease (DKD) is appeared to be higher risk of declining kidney function compared to non-diabetic kidney disease with same magnitude of albuminuria. Epithelial-mesenchymal transition (EMT) program of tubular epithelial cells (TECs) could be important for the production of the extracellular matrix in the kidney. Caveolin-1 (CAV1), dipeptidyl peptidase-4 (DPP-4) and integrin β1 have shown to be involved in EMT program. Here, we found diabetic kidney is prone for albuminuria-induced TECs damage and DPP-4 plays a vital role in such parenchymal damages in diabetic mice. The bovine serum albumin (BSA) injection induced severe TECs damage and altered expression levels of DPP-4, integrin β1, CAV1, and EMT programs including relevant microRNAs in type 1 diabetic CD-1 mice when compared to non-diabetic mice; teneligliptin (TENE) ameliorated these alterations. TENE suppressed the close proximity among DPP-4, integrin β1 and CAV1 in a culture of HK-2 cells. These findings suggest that DPP-4 inhibition can be relevant for combating proteinuric DKD by targeting the EMT program induced by the crosstalk among DPP-4, integrin β1 and CAV1.

Dipeptidyl peptidase-4 inhibitor teneligliptin accelerates recovery from cisplatin-induced acute kidney injury by attenuating inflammation and promoting tubular regeneration.

Cisplatin is an effective chemotherapeutic agent. However, acute kidney injury (AKI) and subsequent kidney function decline limits its use. Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to attenuate kidney injury in some in vivo models, but the mechanisms-of-action in tubule recovery upon AKI remain speculative. We hypothesized that DPP-4 inhibitor teneligliptin (TG) can facilitate kidney recovery after cisplatin-induced AKI. In in vivo experiment, AKI was induced in rats by injecting 5 mg/kg of cisplatin intravenously. Oral administration of 10 mg/kg of TG, once a day, was started just before injecting cisplatin or from Day 5 after cisplatin injection. In an in vitro experiment, proliferation of isolated murine tubular cells was evaluated with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and cell counting. Cell viability was analysed by MTT assay or lactate dehydrogenase (LDH) assay. In in vivo experiments, we found that TG attenuates cisplatin-induced AKI and accelerates kidney recovery after the injury by promoting the proliferation of surviving epithelial cells of the proximal tubule. TG also suppressed intrarenal tumour necrosis factor-α expression, and induced macrophage polarization towards the anti-inflammatory M2 phenotype, both indirectly endorsing tubule recovery upon cisplatin injury. In in vitro experiments, TG directly accelerated the proliferation of primary tubular epithelial cells. Systematic screening of the DPP-4 substrate chemokines in vitro identified CXC chemokine ligand (CXCL)-12 as a promoted mitogenic factor. CXCL12 not only accelerated proliferation but also inhibited cell death of primary tubular epithelial cells after cisplatin exposure. CXC chemokine receptor (CXCR)-4 antagonism abolished the proliferative effect of TG. The DPP-4 inhibitor TG can accelerate tubule regeneration and functional recovery from toxic AKI via an anti-inflammatory effect and probably via inhibition of CXCL12 breakdown. Hence, DPP-4 inhibitors may limit cisplatin-induced nephrotoxicity and improve kidney function in cancer patients.

Validated isocratic liquid chromatographic method for the quantification of teneligliptin in the presence of internal standard

Introduction: Teneligliptin (TGP) is an oral dipeptidyl peptidase inhibitor used for the treatment of type 2 diabetes mellitus. A simple liquid chromatographic method has been established on isocratic mode for the quantification of TGP in pharmaceutical formulations in the presence of internal standard (IS) eplerenone, and the method was validated. Materials and Methods: Methanol and formic acid mixture was used with a flow rate of 0.4 ml/min (detection at 244 nm) using Agilent column on Shimadzu high-performance liquid chromatography system. Results and Discussion: TGP was eluted at 5.099 min and that of IS at 8.535 min. TGP has shown linearity 1–100 μg/mL with regression equation, y = 95722x–6775.4 correlation coefficient 0.9999. The limit of detection and limit of quantification are found to be 0.2598 μg/mL and 0.8134 μg/mL, respectively. Conclusion: It is observed that this reverse-phase ultra-fast liquid chromatography method is accurate and precise and can be used for the estimation of TGP tablets.

Development of Stability Indicating and Robust RP-HPLC Method for Determination of Teneligliptin

A simple and rapid reverse-phase HPLC method was developed for determination of Teneligliptin (TGP) in the presence of its degradation products generated from forced decomposition studies. The HPLC separation was achieved on a C18 ACE column (150x 4.6 mm i.d.; 5 μm) using mobile phase as a mixture of Phosphate buffer pH-7.2 using ortho-phosphoric acid: methanol (30:70v/v). The UV detection was carried out at 245nm at ambient temperature and the flow rate of 1.0 mL/min. The calibration curve was found to be linear in the concentration range of 10-50 μg/mL(r=0.9993). Force degradation study was performed under various conditions like acidic, alkaline, oxidative, photolytic and mass balance calculations were carried out from the degradation results. The developed method was validated as per ICH guidelines with respect to linearity, accuracy, precision, limit of detection and quantification. The robustness of the proposed method was evaluated by the Plackett Burman design. The purity of the degraded sample was checked by peak purity analysis. The peaks of degradation products did not interfere with that of pure Teneligliptin.

Mechanistic study for the simultaneous determination of metformin and teneligliptin in human plasma using hydrophilic interaction liquid chromatography-MS/MS.

A simple, selective and sensitive hydrophilic interaction liquid chromatography-MS/MS method is developed for the simultaneous determination of metformin (MET) and teneligliptin (TEN) in human plasma using deuterated internal standards. The mechanism of retention of analytes was studied by varying the proportion of organic diluent, buffer strength, pH of the mobile phase and temperature. The results showed a mixed-mode mechanism comprising of hydrophilic (partition) and electrostatic interaction (ion exchange) for MET and essentially hydrophilic for TEN. The linear calibration curves were established in the concentration range of 1.0-1000ng/ml for MET and 0.50-750ng/ml for TEN. The method was applied to determine plasma concentration of MET and TEN in healthy subjects.

Quantitative characterization and pharmaceutical compatibility between teneligliptin and widely used excipients by using thermal and liquid chromatography tandem mass spectrometry techniques

The aim of this work was to evaluate the quantitative characterization and pharmaceutical compatibility study of teneligliptin (TNG) with the commonly used excipients for solid dosage form employing thermogravimetric analysis, differential scanning calorimetry, liquid chromatography–mass spectrometer, powder X-ray diffraction, isothermal stress testing, optical microscopy and Fourier transform infrared spectroscopy as a supporting technique to contribute to the interpretation of results. The selected excipients were magnesium stearate (MS), sodium starch glycolate (SSG), croscarmellose sodium (CCS), pregelatinized starch (PS) and microcrystalline cellulose (MCC). On the basis of the DSC results, some interactions were found with TNG–CCS, TNG–MCC, TNG–MS, TNG–SSG and TNG–PS. However, during IST studies less than 3% change in TNG content was observed in all stressed binary mixtures except TNG–CCS, TNG–SSG (< 10%) which showed incompatibility with TNG. These results would be suitable for the formulation development of the solid dosage forms of TNG.

Teneligliptin: DPP-4 inhibitor in the treatment of type II Diabetes Mellitus

The collective review of teneligliptin as an antidibetic drug concerning about the mechanisms of action, pharmacokinetic study, pharmacodynamic study, toxicological study and dose and its contraindication. Teneligliptin is used in the treatment of type II diabetes mellitus. Teneligliptin, a third generation DPP-4 inhibitor, teneligliptin was approved by the US Food and Drug Administration on 2012 based on a large development program. Teneligliptin, a novel DPP-4 inhibitor, exhibits a unique structure characterized by five consecutive rings, which produce a potent and long-lasting effect. Teneligliptin is currently used in cases showing insufficient improvement in glycemic control even after diet control and exercise or a combination of diet control, exercise, and sulfonylurea or thiazolidine-class drugs. In adults, teneligliptin is orally administered at a dosage of 20 mg once daily, which can be increased up to 40 mg per day. Due to the metabolites of this drug are eliminated via renal and hepatic excretion so, adjustable dose is not required to renal impairment patient. In this review, all the clinical data is described. Teneligliptin shows promise in stabilizing glycemic fluctuations throughout the day and consequently suppressing the progression of diabetic complications.

A validated UHPLC-QTOF-MS method for quantification of metformin and teneligliptin in rat plasma: Application to pharmacokinetic interaction study

In this study a sensitive UHPLC-QTOF-MS method was developed and validated for the quantitation of the metformin (MET) and teneligliptin (TEN) in rat plasma using dapagliflozin as an internal standard (IS). Chromatographic separation were carried out on a Acquity UPLC HSS Cyano column (100mm x 2.1mm, 1.8μm) using gradient mobile phase system consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.4mL/min, within a run time of 6min. Protein precipitation method was used as sample preparation approach. Detection of target ions [M+H]+ at m/z 130.1085 for MET, m/z 427.2277 for TEN and m/z 409.1623 for IS was performed at positive ion electrospray ionization mode. Linearity was assessed in the range of 0.98–1000ng/mL for both MET and TEN. The developed assay was validated as per US-FDA and EMA bioanalytical guidelines and successfully applied to pharmacokinetic interaction study in SD rats. A 1.1 fold increment in the AUC levels of MET and TEN was observed when co-administered together in rats.