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Development and Validation of Stability Indicating RP-HPLC Method for the Simultaneous Estimation of Trifluridine and Tipiracilin Bulk and their Combined Dosage form
... Only a limited number of analytical approaches have been documented for the quantification of FTD and TIP. RP-HPLC techniques with UV detection were developed to quantify FTD and TIP in capsules, tablets, and bulk form [11][12][13][14][15][16][17][18]. Nevertheless, the methods that were reported utilized a linear range of 2.5-15 µg/mL and were also time-consuming. FTD, FTY, and TPI measurement in biological fluids using HPLC-UV techniques has only been published in two papers [19,20]. ...
... Moreover, the published assay [19] using larger plasma volume (500 µL), longer analytical run time (8 min), and the LLOQ was much higher, which significantly decrease the efficiency of simultaneous determination of these anti-colorectal cancer drugs in biological fluids. Furthermore, RP-HPLC methods with UV detection were developed to determine FTD and TIP in tablets, capsules, and bulk form [11][12][13][14][15][16][17][18]. However, these published methods adopted time-consuming and linear over range 2.5-15 µg/mL and are not applicable in biological samples or applied to a pharmacokinetic study. ...
A novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous determination of tipiracil (TIP), trifluridine (FTD), and their metabolites, 5-trifluoromethyluracil (FTY) and 5-carboxy-2′-deoxyuridine (5CDU), in rat plasma. This method is highly sensitive, specific, and fast. Paracetamol (PAR) is used as an internal standard (IS). Using acetonitrile-induced protein precipitation, the analytes were extracted from a plasma sample and separated on a Waters BEH C18 (1.7 μm particle size, 50 mm × 2.1 mm ID) column protected by a security guard cartridge (C18, 4 × 2.0 mm). The isocratic mobile phase was made up of methanol and water containing 0.1% formic acid (80:20, v/v) at a flow rate of 0.5 mL/min for 4 min. The quantification was performed using a positive electrospray ionization (ESI) interface and a multiple-reaction monitoring (MRM) mode. The MRM transitions employed were m/z 242.96 → 182.88 for TIP, 296.96 → 116.86 for FTD, 180.98 → 139.85 for FTY, 272.96 → 156.86 for 5CDU, and 151.97 → 92.68 for IS. The validated method complied with the guidelines set by the US-FDA over on a linear concentration range of 5–4000 ng/mL for FTD, FTY, and 5CDU, and 5–1000 ng/mL for TIP. The coefficient of determination (r2) was equal to or greater than 0.997. The corresponding lower limits of detection (LLOD) were 1.5 ng/mL for FTD, FTY, and 5CDU and 1.0 ng/mL for TIP. The recoveries of all analytes from rat plasma ranged from 88.67% to 112.18%, and the mean relative standard deviation (RSD) of accuracy and precision result was less than or equal to 6.84%. FTD, FTY, 5CDU, and TIP demonstrated adequate stability throughout the various circumstances examined. Additionally, no matrix effects were identified for any of the analytes. The assay was effectively utilized to conduct a pharmacokinetic study in rats following the oral administration of FTD and TIP at a dosage of 5.6 mg/kg, with a ratio of 1:0.5 for FTD and TIP, respectively. This indicates that the suggested approach is suitable for future clinical research. The pharmacokinetic parameters Cmax (maximum concentration), Tmax (time to reach maximum concentration), t1/2 (half-life), AUC0-24 (area under the concentration–time curve from 0 to 24 h), AUC total (total area under the concentration–time curve), Ke (elimination rate constant), Vd (volume of distribution), and CL (clearance) of all analytes were assessed. The assay developed exhibits significant advancements compared to earlier bioanalytical methods documented in the literature. These improvements include high sensitivity, specificity, and efficacy in high throughput analysis of complex matrices. Additionally, the assay offers a shorter run time and smaller sample volume (50 μL).
... Literature survey reveals that liquid chromatographic methods [5][6][7][8][9][10][11][12] were developed for the simultaneous determination of Trifluridine and Tipiracil in pharmaceutical dosage forms as well as in human plasma [13]. Asha., et al. developed a LC-MS/MS method [14] for the estimation of Trifluridine and Tipiracil in tablet dosage forms. ...
Trifluridine, also known as trifluoro thymidine is an anti-viral drug used for the treatment of viral infections of eyes. A new validated RP-UFLC method has been developed for the determination of Trifluridine using Shimadzu Model UFLC system SPD-M20A 230V with PDA detector and LC- 20AD pumps and C18 Shim-pack GWS HPLC packed column (250 mm × 4.60 mm, 5 μm) in in ophthalmic preparations. Mobile phase consisting of acetonitrile: 10 mM potasium dihydrogen phosphate buffer adjusted pH to 3.5 with dilute tri fluro acetic acid (70:30 v/v) (Isocratic mode) with 1.0 mL/min flow rate (Detection wavelength 272 nm) are the chromatographic conditions for the present study. Trifluridine obeys Beer-Lambert’s law over the concentration range 0.1-120 µg/mL with linear regression equation y = 46195x – 1876.5 (R² = 0.9998) and the method was validated as per ICH guidelines. The LOQ and LOD values were found to be 0.08934 µg/mL and 0.0257 µg/mL respectively. Trifluridine was exposed to different stress conditions such as alkaline hydrolysis, acidic hydrolysis, oxidation and thermal degradation and the assay was carried out. The proposed method is simple, precise, accurate, robust and used for the routine analysis of marketed formulations.
Fenugreek (Trigonella foeum-graecum L.) has been used in Iranian traditional medicine for treatment of different kinds of inflammation disorders. In the present study, anti-inflammatory activity of the methanolic extract of the plant (at doses of 100, 200 and 400 mg/kg) were studied using carrageenan-induced edema method and compared with the effects of dexamethasone and ibuprofen. Various concentrations of the plant extract (2-5%) were also prepared as a cream and their anti-inflammatory effects were evaluated and compared with 1% hydrocortisone ointment as the reference drug. The results showed that the inhibition of edema by the plant extract at doses of 100 and 200 mg/kg were significantly different from the control group. This activity of the plant at doses of 100 and 200 was not significantly different from those of ibuprofen and dexamethasone. Among the prepared formulations of the plant, 3 and 5% creams of the fenugreek showed the most inhibition of edema which were not significant from hydrocortisone ointment. The results of the present study, therefore, support the traditional uses of this plant for inflammations. However, more research is needed for its use in clinical studies.
Fenugreek (Trigonella foenum-graecum L. seed) is a food with traditional medicinal use in diabetes. Beneficial effects have been demonstrated in diabetic animals and both insulin-dependent and non-insulin-dependent diabetic subjects. Effects of a lipid extract A, crude ethanolic extract B, further sub-fractions of B (saponin-free C, saponin D and sapogenin E) and a gum fibre fraction F on intestinal sodium-dependent glucose uptake were investigated in vitro using rabbit intestinal brush border membrane vesicles. All fractions except A inhibited glucose-uptake at 0.33 and/or 3.3 mg/mL (p < 0.001). Greatest inhibition was observed with fractions D and E. Diosgenin and trigonelline (compounds reported in fenugreek) also inhibited glucose-uptake (IC50 values approximately 3 mg/ml, equivalent to 8 mM and 19 mM respectively) but did not account for the activity of the crude extracts. Fenugreek extracts had no effect on basal levels of glycogen phosphorylase a (HGPa) activity in rat hepatocyte suspensions. However fractions C and E caused a marginal but statistically significant inhibition (18.9 and 15.1% respectively, p < 0.05) of glucagon induction of this enzyme suggesting a glucagon-antagonist effect. Diosgenin (1.65 mg/ml; 4 mM) inhibited glucagon-induced HGPa activity by 20% (p < 0.05), and was more effective than trigonelline (non significant inhibition of 9.4% at 1.65 mg/ml, 10 mM).
Fenugreek has a long history of medical uses in Ayurvedic and Chinese medicine, and has been used for numerous indications, including labor induction, aiding digestion, and as a general tonic to improve metabolism and health. Preliminary animal and human trials suggest possible hypoglycemic and antihyperlipidemic properties of oral fenugreek seed powder.
Trigonella foenum-graecum (Family- Fabaeace) plant is eaten in India since long. It is also known as Methi and used in Ayurvedic medicines for the treatment of wounds, abscesses, arthritis, bronchitis, and digestive disorders. In present investigation an attempt has been made for the standardization and Phytochemical evaluation of fenugreek seeds. The standardization evaluation comprises of detailed macroscopy, powder microscopy, and fluorescence analysis, physic-chemical constants such as ash value, extractive values, successive solvent extraction, moisture contents, foaming index and swelling index. The seeds extracts were also subjected to preliminary Phytochemical screening. The data obtained in present study will serve as valuable tool for identification, authentication and detection of adulterants, standardization and quality control of the drug.
Fenugreek seed ( Trigonella foenum-graecum L.) is used as an herbal medicine for treating metabolic and nutritive dysfunctions. To determine if this plant has other beneficial effects, we tested the inhibitory activities of a methanol (MeOH) extract of fenugreek seed on the production of inflammatory cytokines and melanin synthesis in cultured cell lines in vitro. The MeOH extract inhibited the production of phorbol-12-myristate-13-acetate-induced inflammatory cytokines such as tumor necrosis factor (TNF)-α in cultured THP-1 cells, and also restrained the intracellular synthesis of melanin in murine melanoma B16F1 cells. We isolated three active constituents from fenugreek seed extracts. These were identified as the steroidal saponins 26- O-β-D-glucopyranosyl-(25 R)-furost-5(6)-en-3 β,22 β,26-triol-3- O-α-L-rhamno-pyranosyl-(1'' → 2')-O-[β-D-glucopyranosyl-(1''' → 6')- O]-β-D-glucopyranoside 1, minutoside B 2, and pseudoprotodioscin 3. Compounds 1 and 2 strongly suppressed the production of inflammatory cytokines, whereas 3 showed a weaker suppressing effect. Melanogenesis in B16F1 cells was significantly suppressed by 1 and 3, and weakly suppressed by 2. All three compounds showed moderate cytotoxicities. These results indicate that fenugreek extract and its active constituents could protect against skin damage.
Analgesic and anti-inflammatory activities of Trigonellafoenum-graecum (seed) extract
- Agrawal Rajendra Vyassavita
- Prasad
- Trivedipiyush Solankipooja
VyasSavita, Agrawal Rajendra Prasad, SolankiPooja, TrivediPiyush, "Analgesic and anti-inflammatory
activities of Trigonellafoenum-graecum (seed) extract", Acta poloniaepharmaceutica -drug research,
65 (4), 2008, 473-476.
Anti-arthritic and vascular protective effects of fenugreek, boswelliaserrata and acacia catechu alone and in combinations
- S Vyasamit
- Patel Nailesh
- G Panchalaashish
- H Patel Rameshwar
- Patel Madhabhai
VyasAmit S., Patel Nailesh G., PanchalAashish H., Patel Rameshwar K. and Patel Madhabhai M.,
"Anti-arthritic and vascular protective effects of fenugreek, boswelliaserrata and acacia catechu alone
and in combinations", An international journal of pharmaceutical sciences, 1(2), 2010, 95-111.