Development and Validation of RP-HPLC Method for Simultaneous Estimation of Glimepiride and Sildenafil Citrate in Rat Plasma-Application to Pharmacokinetic Studies

Tripathi, Alok Shiomurti; Dewani, Anil P.; Shelke, P. G.; Bakal, Ravindra L.; Chandewar, A. V.; Mazumder, Papiya Mitra

doi:10.1055/s-0033-1349865

Cited by 12 publications

(6 citation statements)

References 10 publications

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“…Plasma was separated by centrifugation and stored at −20°C until analysis. Aliquots of 0.1 mL serum samples were processed and analyzed for GLIM and SIL concentration using an HPLC-UV method developed in our laboratory [18,19].…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies

Tripathi¹,

Timiri

Mazumder

et al. 2015

J Mol Model

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The present study evaluates possible drug interactions between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction based on molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg kg(-1), i.p.) and was confirmed by assessing blood and urine biochemical parameters 28 days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and SIL (2.5 mg kg(-1), p.o.) on the 29th and 70th day of the protocol. Possible drug interaction was assessed by evaluating the plasma drug concentration using HPLC-UV and changes in biochemical parameters in blood and urine were also determined. The mechanism of the interaction was postulated from the results of a molecular modeling study using the Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in blood and urine biochemical parameters in STZ-treated groups. The concentration of SIL increased significantly (P < 0.001) in rat plasma when co-administered with GLIM on the 70th day of the protocol. Molecular modeling revealed important interactions with rat serum albumin and CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger hydrogen bond than SIL with polar contacts and hydrophobic interactions. The present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals, and the mechanism is supported by molecular modeling studies.

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Section: Pharmacokinetic Studymentioning

confidence: 99%

Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies

Tripathi¹,

Timiri

Mazumder

et al. 2015

J Mol Model

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“…Glimepiride, a third‐generation sulfonylurea hypoglycemic agent, has been used for the treatment of type 2 noninsulin‐dependent diabetes mellitus 16,17 . The glimepiride metabolite appears to be formed by CYP2C9 in liver microsomes 18 .…”

Section: Introductionmentioning

confidence: 99%

Metabolic study of ginsenoside Rg3 and glimepiride in type 2 diabetic rats by liquid chromatography coupled with quadrupole‐Orbitrap mass spectrometry

Yang

et al. 2021

Rapid Comm Mass Spectrometry

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Rationale Ginsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes. Methods An in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in the different groups was analyzed by ultra‐performance liquid chromatography coupled with quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap MS). Results The results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1–M5) of glimepiride were found, and they were named 3N‐hydroxyglimepiride, hydroxyglimepiride, 1,2‐epoxy ether‐3‐hydroxyglimepiride, 1N‐hydroxyglimepiride and 1N,2C,S,O,O‐epoxy ether‐3‐hydroxyglimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2. Conclusions An in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.

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“…Many quantitative methods have been developed for the determination of GLM in biological fluids, such as high-performance liquid chromatography with ultraviolet detection (HPLC-UV) which showed, relatively, very high quantitative limits, that are far from the actual amount of non-metabolized GLM [6][7][8][9]. Also, liquid chromatography-tandem mass spectrometry (LC-MS) has been developed for its determination [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Also, liquid chromatography-tandem mass spectrometry (LC-MS) has been developed for its determination [10][11][12][13]. Generally, two extraction procedures were used for the recovery of GLM from plasma, including liquid-liquid extraction (LLE) [9] and solid-phase extraction (SPE) [8,10]. The major limitation of LLE that it consumes a large quantity of organic solvent and leads to environmental pollution.…”

Section: Introductionmentioning

confidence: 99%

LC-MS/MS determination of glimepiride in human plasma with a high recovery at picogram scale: Pharmacokinetic study after oral administration

Kammoun

Awan

Elawady

et al. 2021

AChrom

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Although glimepiride (GLM) is the first-line treatment of Type II diabetes, low extraction recovery is still a significant limitation in previous plasma analysis methods. An optimized solid-phase extraction method of GLM in human plasma with excellent extraction recovery, 100 ± 0.06%, was achieved using liquid chromatography-electrospray ionization tandem mass spectrometry and Gliclazide (GLZ) as an internal standard. GLM was extracted from 100 µL plasma sample using Sep-Pak® vac 1cc (100 mg) C18 column and methylene chloride: methanol (2: 1, v/v) as eluant. Both GLM and GLZ were monitored by a triple quad mass spectrometer applying positive multiple reaction monitoring mode (+MRM). The protonated precursor ions and product ions of GLM and GLZ were m/z 491(352), and m/z 324 (127), respectively. The detection and measurement of low levels of GLM in human plasma reached to picogram range (limit of detection (LOD) = 60 pg/mL, limit of quantification (LOQ) = 200 pg/mL). The method was validated in terms of selectivity, linearity, recovery, accuracy, and precision. The method was successfully applied to the pharmacokinetic study of GLM following oral administration of 1 mg GLM tablets to 12 healthy volunteers.

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Development and Validation of RP-HPLC Method for Simultaneous Estimation of Glimepiride and Sildenafil Citrate in Rat Plasma-Application to Pharmacokinetic Studies

Cited by 12 publications

References 10 publications

Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies

Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies

Metabolic study of ginsenoside Rg3 and glimepiride in type 2 diabetic rats by liquid chromatography coupled with quadrupole‐Orbitrap mass spectrometry

LC-MS/MS determination of glimepiride in human plasma with a high recovery at picogram scale: Pharmacokinetic study after oral administration

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