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Review Article Open Access
Volume 4 | Issue 1 | DOI: https://doi.org/10.33696/Nanotechnol.4.037

The Methods of Analysis for Determination of Metformin and Glimepiride in Different Matrices

  • 1Medicinal Chemistry Department, Faculty of Pharmacy, Zagazig University, Sharkia, 44519, Egypt
+ Affiliations - Affiliations

*Corresponding Author

Mahmoud M. Sebaiy, mmsebaiy@zu.edu.eg, sebaiym@gmail.com

Received Date: December 05, 2022

Accepted Date: March 21, 2023

Abstract

In this literature review, we will introduce pharmacology in addition to most of the up-to-date reported methods that have been developed for determination of important oral hypoglycemic drugs which are metformin and glimepiride in their pure forms, combined forms with other drugs, combined forms with degradation products, and in biological samples.

Keywords

Literature review, Metformin, Glimepiride; Degradation products, Biological samples

Introduction

Diabetes mellitus is characterized by abnormally high levels of sugar (glucose) in the blood, When the amount of glucose in the blood increases, e.g., after a meal, it triggers the release of the hormone insulin from the pancreas. Insulin stimulates muscle and fat cells to remove glucose from the blood and stimulates the liver to metabolize glucose, causing the blood sugar level to decrease to normal level. In people with diabetes, blood sugar levels remain high. This may be because insulin is not being produced at all, or is not made at sufficient levels, or is not as effective as it should be. The most common forms of diabetes are type-1 diabetes (5%), which is an autoimmune disorder, and type 2 diabetes (95%), which is associated with obesity. Gestational diabetes is a form of diabetes that occurs in pregnancy, and other forms of diabetes are very rare and are caused by a single gene mutation [1].

Metformin (MTF, as seen in Figure 1), sold under the brand name Glucophage, among others, is the first-line medication for the treatment of type 2 diabetes. MTF is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. MTF decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. MTF does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With MTF therapy, insulin secretion remains unchanged while fasting insulin levels and daylong plasma insulin response may decrease [2-4].

Glimepiride (GLM, as depicted in Figure 1) is indicated for the management of type 2 diabetes in adults as an adjunct to diet and exercise to improve glycemic control as monotherapy. It may also be indicated for use in combination with metformin or insulin to lower blood glucose in patients with type 2 diabetes whose high blood sugar levels cannot be controlled by diet and exercise in conjunction with an oral hypoglycemic (a drug used to lower blood sugar levels) agent alone [5].

Its mechanism of action is based on ATP-sensitive potassium channels on pancreatic beta cells that are gated by intracellular ATP and ADP. The hetero-octomeric complex of the channel is composed of four pore-forming Kir6.2 subunits and 4 regulatory sulfonylurea receptor (SUR) subunits. Alternative splicing allows the formation of channels composed of varying subunit isoforms expressed at different concentrations in different tissues [7]. In pancreatic beta cells, ATP-sensitive K channels play a role as essential metabolic sensors and regulators that couple membrane excitability with glucose-stimulated insulin secretion (GSIS). When there is a decrease in the ATP:ADP ratio, the channels are activated and open, leading to K+ efflux from the cell, membrane hyperpolarization, and suppression of insulin secretion. In contrast, increased uptake of glucose into the cell leads to elevated intracellular ATP:ADP ratio, leading to the closure of channels and membrane depolarization. Depolarization leads to activation and opening of the voltage-dependent Ca2+ channels and consequently an influx of calcium ions into the cell. Elevated intracellular calcium levels cause the contraction of the filaments of actomyosin responsible for the exocytosis of insulin granules stored in vesicles [3]. GLM blocks the ATP-sensitive potassium channel by binding non-specifically to the B sites of both sulfonylurea receptor-1 (SUR1) and sulfonylurea receptor-2A (SUR2A) subunits as well as the A site of SUR1 subunit of the channel to promote insulin secretion from the beta cell [6].

Review of Analytical Methods

Various techniques were used for the analysis of MTF and GLM in its pure forms, in pharmaceutical formulations and in biological fluids. The available reported methods in the literature can be summarized as follows:

Spectroscopic Methods

Spectrophotometric methods

Ref.

LOD

Linearity range

λmax (nm)

Method or reagent

Matrix

Drugs

[7]

------------

8-18 μg/mL

570

Ninhydrin in     alkaline medium

Tablets

MTF

[8]

0.167 & 0.320 μg/mL

5–30 μg/mL.0

233 & 238

Q – Absorption ratio method

Tablets

MTF, Anagliptin

[9]

-------------

2-12 μg/mL

295

Charge-transfer complex with iodine

Tablets

MTF

[10]

0.083

µg/mL

0.5-4 µg/mL

385

Oxidation using sodium hypochlorite in alkaline medium

Tablets and industrial waste water

MTF

[11]

------------

0.5-2 mg/mL

540

Cu2+ in basic medium

Tablets

MTF

[12]

0.4 μg/mL

5-30 μg/mL

249

UV spectrophotometry.

Tablets

GLM

[13]

1.311 mg/L

2-40 mg/L

279.0, 257.5 & 256.3

Derivative UV  spectrophotometry

Tablets

GLM

[14]

0.4 μg/mL

1- 500 μg/mL

263.3–268.2

Derivative UV spectrophotometry

Tablets

GLM

[15]

------------

40–160 μg/mL

413.5

2,3,5-Triphenyl-2H-tetrazolium chloride in basic media

Tablets

GLM

[16]

2.6 μg/mL

2.8 μg/mL

 

10–80 μg/mL

20120 μg/mL

        •  

843

415

1-Charge-transfer complex using TCNQ

2-Ion-pair complex using bromo thymol blue

Tablets

GLM

[17]

0.088 μg/mL

0.981-9.812 μg/mL

416

Ion-pair complex formation using bromocresol green

Tablets

GLM

[18]

0.35 μg/mL

0.5-22 μg/mL

231

UV spectrophotometry

Tablets

GLM

Spectrofluorometric methods

Ref.

LOD

Linearity range

λem

λmax

Fluorogenic method

Matrix

Drug

[11]

------------

20-200 μg/mL

520

450

Chrysenequinone in alkaline medium

Tablets

MTF

[19]

0.01 μg/mL

 

0.04-1.2 μg/mL

416 

240

9,10-phenanthraquinone in alkaline media

Tablets

MTF, Glibenclamide

 

Chromatographic methods

HPLC-UV methods

Drugs

Matrix

Column

Mobile phase

UV-Detector (nm)

Linearity range

LOD

Ref.

MTF

Tablets & formulated microspheres

phenomenex C18 ODS (5 μ, 250 × 4.60 mm)

Acetonitrile:phosphate buffer (65:35) pH adjusted to 5.75 with o-phosphoric acid

233

0-25 μg/mL

--------

[20]

MTF

Human plasma

RP C18 (250 × 4.6 mm, 5 μm)

34% acetonitrile & 66% aqueous phase, containing 10 mM KH2PO4 and 10 mM SLS.

233 

0.125-2.5 μg/mL

62 ng/mL

[21]

MTF,  nateglinide

Tablets

Inertsil C18-ODS 3V (250 × 4.6 mm, 5 μm)

Phosphate buffer (pH4.0): Acetonitrile: methanol (30:60:10)

221

60-140 μg/mL

2.18 μg/mL

[22]

MTF, Gliclazide & GLM

Tablets

Thermo Scientific® BDS Hypersil C8  (5µm, 2.50 x 4.60 mm)

MeOH : 0.025M KH2PO4 adjusted to pH 3.20 using ortho - phosphoric acid (70 : 30, v/v)

235

5-100 µg/mL

0.05 (MET),    0.11 μg/mL (GLM)

[23]

MTF, ertugliflozin

Tablets

Kromasil C18 (150 mm × 4.6 mm, 5 μm)

0.1% ortho-phosphoric acid buffer (pH 2.7):acetonitrile (65:35% v/v)

224

62.5-375 μg/mL

0.87

 μg/mL

[24]

MTF, Repaglinide

Tablets

XBridge C18 column (4.6 x 150 mm, 3.5 μm)

Potassium dihyrogen ortho phosphate (2.2 pH): Acetonitrile (35:65%v/v)

240

5-50 μg/mL

0.018 μg/mL

[25]

MTF, pioglitazone & GLM

Tablets

Inertsil-ODS-3 C18 (250 × 4.60 mm, 5 µm)

Methanol–phosphate buffer (pH 4.3) in the ratio of 75:25 v/v

258

10-5000 (MET),

1-10 μg/mL (GLM)

--------

[26]

MTF, atorvastatin & GLM

Tablets

Grace Smart Altima C8 (250 × 4.6 mm, 5 μm)

Acetonitrile : phosphate buffer (60 : 40 (v/v), pH 3.0)

235 

20- 200 µg/mL

--------

[27]

MTF, Sitagliptin

Tablets

Li-chrosphere-100 C18 ODS (250 × 4.6 mm, 5 μm)

Methanol: potassium di-hydrogen phosphate buffer at a ratio of 70:30 v/v

266

20-100 μg/mL

 

0.14 μg/mL

[28]

MTF

Tablets

RP C18 (250 mm x 4.6 mm, 5.0 µm)

34% acetonitrile and 66% 10 mM KH2PO4 and 10 mM sodium lauryl sulfate (pH 5.2)

233

2.5-20 µg/mL

0.1

µg/mL

[29]

MTF, gliclazide

Tablets

Alltima CN (250 mm × 4.6 mm x5μm)

20 mM ammonium formate buffer (pH 3.5) and acetonitrile (45:55, v/v)

227

2.5-150 μg/mL

0.8 μg/mL

 

[30]

GLM

Self-nanoemulsifying powder (SNEP) formulation

octadesyl silane (ODS) (250 x 4.6 mm, 5μm)

Acetonitrile: 0.2 M phosphate buffer (pH= 7.4) 40:60 v/v

228

0.2-2 μg/mL

0.38 μg/mL

[31]

GLM

Rat serum samples

LiChrosphere 100 RP 18 e (125 × 4.0 mm, 5 µm)

MeOH: 10mM Phosphate buffer (80:20 v/v) adjusted to pH 3.0 with orthophosphoric acid

230

0.5-500 μg/mL

0.15 μg/mL

[32]

GLM

Tablets

Hypersil C18 (15 cm x 3.9 mm)

Acetonitrile 0.05 M monobasic potassium phosphate (pH 6.0) 40:60 v/v

210

10–40 μg/mL

0.8 μg/mL

[33]

GLM

Tablets

Lichrosorb RP-18  (125 x 4 mm, 5µm)

Acetonitrile-water-glacial acetic acid (550:450:0.6 v/v)

230

15-120 μg/mL

4 ng

[34]

GLM

Tablets

spherisorb S5NH2

(250 mm x 4.6 mm, 5 μm)

40% acetonitrile and 60% aqueous acetate buffer (5.0 mM at pH 6.3)

228

50.0 μg/L - 6.0 mg/L

15.0 μg/L

[35]

MTF, pioglitazone & GLM

Tablets

Phenomenex-ODS-3 C18  (250 × 4.60 mm, 5 μm)

MeOH:acetonitrile:15 mM KHPO4 (pH 4), 40:35:25

240

0.2-50 (MET),

0.2-30 μg/mL (GLM)

0.04 (MTF),

0.08 μg/mL (GLM)

[36]

MTF, pioglitazone & GLM

Human plasma

MAGELLEN 5U C18 (5 μm, 150 mm × 4.60 mm)

MeOH-0.025 M KH2PO4 adjusted to PH 3.20 using O-phosphoric acid (85:15, v/v)

235

2.50-100 μg/mL

0.05 (MET),    0.10 μg/mL (GLM)

[37]

 

2.2: HPLC-MS methods

Drug

Matrix

Column

Mobile phase

Detector

Linearity range

LOD

Ref.

MTF, canagliflozin

Human plasma

C18 column (50 mm × 4.6 mm, 5 µm)

0.1% formic acid and acetonitrile (60:40, v/v)

MS

50–5000 ng/mL

15 ng/mL

[38]

MTF,  Empagliflozin

Tablets

Bridged Ethylene Hybrid C18 (50 mm × 2.1 mm, 1.7 μm)

0.1% aqueous formic acid: acetonitrile (75:25, v/v)

MS

50–25,000 ng/mL

7.3– 21.9 ng/mL

[39]

MTF

Human plasma

a Zorbax SB C8 (150 mm × 4.6 mm, 5 μm)

Acetonitrile−water− formic acid (70:30:1, v/v)

MS

2.0–2000 ng/mL

0.7 ng/mL

[40]

MTF

Human plasma

 Nucleosil C18 (5 μm, 50 mm × 4.6 mm)

Acetonitrile: methanol:10 mM ammonium acetate pH 7.0 (20:20:60, v/v/v)

MS

1–2000 ng/mL

250 pg/mL

[41]

MTF,  gliclazide

Human plasma

Hypersil BDS C18 (50 mm × 2.1 mm, 3 µm)

Methanol–water (containing 1% formic acid)– acetonitrile (30: 31: 39, v/v/v)

MS

7.8–4678.9 ng/mL

2.6 ng/mL

[42]

MTF,  vildagliptin

Human plasma

Atlantis HILIC Silica (150 × 2.1 mm, 3μm)

20% water and 80% acetonitrile/water solution 95:5 (v/v), containing both 0.1% formic acid and 3mM ammonium formate.

MS

5-500 ng /mL

1.5 ng/mL

[43]

GLM

Human plasma

5 µm (50 mm × 2.1 mm, i.d.) C18 XTerra column

Ammonium acetate buffer (0.02 M, pH = 3.5): acetonitrile: methanol in the ratio of 40:35:25 (v/v)

MS

5.0– 500.0 ng/mL

1.5  ng/ml.

[44]

GLM

Human plasma

ACE 5C18, 50×4 mm, 5μm column

200mL water, 450mL acetonitrile, 350mL methanol, 0.6mL glacial acetic acid

MS

5–1,000 ng/mL

1.5 ng/mL

[45]

GLM

Human plasma

Zorbax Eclipse Plus C18 column (3.5 µm, 4.6 × 100 mm)

Acetonitrile: 0.1% formic in water (70: 30, v/v)

MS

2.0–650 ng/mL

60 pg/mL

[46]

GLM

Human Plasma

BEH C18 1.7µm (2.1x50 mm).

A: 30% (Ammonium formate 0.1 %) B:70% Acetonitrile

MS

1– 100 ng/mL

0.33 ng/mL

[47]

 

HPTLC methods

Drug

Matrix

Stationary phase

Mobile phase

Detector

Linearity range

LOD

Ref.

GLM, Empagliflozin & Linagliptin

Tablets

Aluminum plates precoated with silica gel 60 F254

Toluene: methanol: ethyl acetate (4: 3: 2 v/v/v)

Reflectance/fluorescence mode at λmax 228 nm and λem 320 nm

2.61–60 ng/band

1.84 ng/band

[48]

MTF, Atorvastatin & GLM

Tablets

Silica gel 60 F254

Water: methanol: ammonium sulphate (1: 1: 4 v/v/v)

Densitometric

detection at 237 nm

200-700 (MET),

600-2100 ng/spot (GLM)

100 (MET),

500 ng/spot (GLM)

[49]

MTF, GLM

 

Tablets

TLC aluminium plates precoated with silica gel 60 F254

0.5% Ammonium Sulfate: Methanol (7.5:2.5 v/v)

Densitometric

detection at 228 nm

200-700 (MET),

600-2100 ng/band (GLM)

0.32 (MET),

0.05 ng/band (GLM)

[50]

MTF, Nateglinide,

 

Tablets

TLC aluminium plates precoated with silica gel 60 F254

Chloroform:ethyl acetate:acetic acid (4:6:0.1 v/v/v)

Reflectance/absorbance mode at 216 nm

500–3000 ng/band

 

0.022 ng/band

[51]

GLM, Rosiglitazone

Tablets

Silica gel 60 F254

 

Methanol: toluene: ethyl acetate (1:8:1, v/v/v)

Densitometric

detection at 228 nm

100 - 1500 ng/spot

30 ng/spot

[52]

 

Electrochemical methods

Drug

Matrix

Electrode

Linearity range

LOD

Ref.

MTF

Tablets

Glassy carbon

1.0 nmol L−1 - 1.0 μmol L−1

0.3 nmol L−1.

[53]

MTF

Tablets

Carbon paste

0.1 - 80 μM

0.014 μM

[54]

MTF

Tablets

Glassy carbon

10 - 70 μM

0.7 μM

[55]

MTF

Tablets

Glassy carbon

0.5 - 25 μM

0.12 μM

[56]

MTF

sol–gel matrix

Citrate-capped gold nanoparticle

0.02 - 80 ng mL−1

0.005 ng mL−1

[57]

MTF

Tablets

Carbon paste

0.1–65 μM

30 nM

[58]

MTF

Tablets

Pencil graphite

0.1–1000 µM

6.8 nM

[59]

MTF

Urine

Mercury drop

 

5×10−8 - 4×10−6 mol l−1

1.8 × 10−8 mol l−1

[60]

MTF

 

Tablets & human serum

Carbon paste

10.4-1125.0 µM

3.4 µM

[61]

MTF

Tablets & urine

Carbon paste

50 nM - 60 μM

9 nM

[62]

MTF

Tablets

CB[6]-modified gold electrode

10 pmol/L - 20 nmol/L

1.35 pmol/L

[63]

MTF

Biological samples

Copper hydroxide - carbon ionic liquid electrode

1 µM–4 mM

0.5 µM

[64]

GLM

Tablets

Glassy carbon

Carbon paste

1.0×10–5 - 3.2×10–5 mol l–1

2.0×10–6 - 1.5×10–5 mol l–1

2.0 × 10–6 mol l–1

7.5 × 10–7 mol l–1

[65]

GLM, Valsartan

--------

Hanging mercury drop electrode (HMDE)

0.25x10-7 - 3.25x10-7 M

3.48x10-8 M

[66]

By the end of this literature review, we would like to emphasize that we continue in our current project to provide an updated review on diseases and drugs chemistry that help the humanity all over the world [67-102].

Conclusion

In this literature review, we shed the light on pharmacology of metformin and glimepiride in addition to most of up-to-date reported methods related to their determination in their pure forms, combined forms with other drugs, combined forms with degradation products, and in biological samples.

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41. Wang Y, Tang Y, Gu J, Fawcett JP, Bai X. Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitation of metformin in human plasma. Journal of Chromatography B. 2004 Sep 5;808(2):215-9.

42. Zhong GP, Bi HC, Zhou S, Chen X, Huang M. Simultaneous determination of metformin and gliclazide in human plasma by liquid chromatography-tandem mass spectrometry: application to a bioequivalence study of two formulations in healthy volunteers. Journal of Mass Spectrometry. 2005 Nov;40(11):1462-71.

43. Pontarolo R, Gimenez AC, de Francisco TM, Ribeiro RP, Pontes FL, et al.Simultaneous determination of metformin and vildagliptin in human plasma by a HILIC-MS/MS method. Journal of Chromatography B. 2014 Aug 15;965:133-41.

44. Salem II, Idrees J, Al Tamimi JI. Determination of glimepiride in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry. Journal of Chromatography B. 2004 Jan 5;799(1):103-9.

45. Yüzüak N, Özden T, Eren S, Özilhan S. Determination of glimepiride in human plasma by LC–MS–MS. Chromatographia. 2007 Sep;66:165-8.

46. Kammoun AK, Awan ZA, Elawady T, Khedr A, El-Awady MI. LC-MS/MS determination of glimepiride in human plasma with a high recovery at picogram scale: Pharmacokinetic study after oral administration. Acta Chromatographica. 2022;34(1).

47. Ayad MM, Hosny MM, El-Sayed HM, Elwan MG. A Validated Bioanalytical Method for Determination of Glimepiride in Human Plasma Using UPLC-MS/MS.

48. Abbas NS, Derayea SM, Omar MA, Saleh GA. Innovative TLC-densitometric method with fluorescent detection for simultaneous determination of ternary anti-diabetic mixture in pharmaceutical formulations and human plasma. Microchemical Journal. 2021 Jun 1;165:106131.

49. Dhaneshwar SR, Salunkhe JV, Bhusari VK. Validated HPTLC method for simultaneous estimation of metformin hydrochloride, atorvastatin and glimepiride in bulk drug and formulation. Journal of Analytical and Aioanalytical Techniques. 2010;1(3):1-5.

50. Patel KK, Karkhanis VV, Gajjar SS. Development and validation of stability indicating HPTLC method for estimation of glimepiride and metformin hydrochloride. International Journal of Pharmaceutical Sciences and Research. 2015 Mar 1;6(3):1222.

51. Thomas AB, Patil SD, Nanda RK, Kothapalli LP, Bhosle SS, Deshpande AD. Stability-indicating HPTLC method for simultaneous determination of nateglinide and metformin hydrochloride in pharmaceutical dosage form. Saudi Pharmaceutical Journal. 2011 Oct 1;19(4):221-31.

52. Dhole SM, Khedekar PB, Amnerkar ND. Development and validation of hptlc densitometry method for simultaneous estimation of rosiglitazone and glimepiride in fixed tablet dosage form. Journal of the Chilean Chemical Society. 2013;58(2):1663-6.

53. Ghanbari MH, Sharafi P, Nayebossadr S, Norouzi Z. Utilizing a nanocomposite consisting of zinc ferrite, copper oxide, and gold nanoparticles in the fabrication of a metformin electrochemical sensor supported on a glassy carbon electrode. Microchimica Acta. 2020 Oct;187:1-1.

54. Mirzajani R, Karimi S. Preparation of ?-Fe2O3/hydroxyapatite/Cu (II) magnetic nanocomposite and its application for electrochemical detection of metformin in urine and pharmaceutical samples. Sensors and Actuators B: Chemical. 2018 Oct 1;270:405-16.

55. Gorska A, Paczosa?Bator B, Wyrwa J, Piech R. New Electrochemical Sensor of Prolonged Application for Metformin Determination Based on Hydrated Ruthenium Dioxide?Carbon Black?Nafion Modified Glassy Carbon Electrode. Electroanalysis. 2020 Aug;32(8):1875-84.

56. Hadi M, Poorgholi H, Mostaanzadeh H. Determination oF metformin at metal-organic framework (Cu-BTC) Nanocrystals/multi-walled carbon nanotubes modified glassy carbon electrode. South African Journal of Chemistry. 2016 Jan 1;69(1):132-9.

57. Roy E, Patra S, Madhuri R, Sharma PK. Gold nanoparticle mediated designing of non-hydrolytic sol-gel cross-linked metformin imprinted polymer network: A theoretical and experimental study. Talanta. 2014 Mar 1;120:198-207.

58. Dehdashtian S, Gholivand MB, Shamsipur M, Karimi Z. A nano sized functionalized mesoporous silica modified carbon paste electrode as a novel, simple, robust and selective anti-diabetic metformin sensor. Sensors and Actuators B: Chemical. 2015 Dec 31;221:807-15.

59. Nezhadali A, Khalili Z. Computer-aided study and multivariate optimization of nanomolar metformin hydrochloride analysis using molecularly imprinted polymer electrochemical sensor based on silver nanoparticles. Journal of Materials Science: Materials in Electronics. 2021 Dec;32:27171-83.

60. Skrzypek S, Mir?eski V, Ciesielski W, Soko?owski A, Zakrzewski R. Direct determination of metformin in urine by adsorptive catalytic square-wave voltammetry. Journal of Pharmaceutical and Biomedical Analysis. 2007 Oct 18;45(2):275-81.

61. Hassasi S, Hassaninejad-Darzi SK, Vahid A. Production of copper-graphene nanocomposite as a voltammetric sensor for determination of anti-diabetic metformin using response surface methodology. Microchemical Journal. 2022 Jan 1;172:106877.

62. Gholivand MB, Mohammadi-Behzad L. Differential pulse voltammetric determination of metformin using copper-loaded activated charcoal modified electrode. Analytical Biochemistry. 2013 Jul 1;438(1):53-60.

63. Wang Y, Ding L, Yu H, Liang F. Cucurbit [6] uril functionalized gold nanoparticles and electrode for the detection of metformin drug. Chinese Chemical Letters. 2022 Jan 1;33(1):283-7.

64. Momeni S, Farrokhnia M, Karimi S, Nabipour I. Copper hydroxide nanostructure-modified carbon ionic liquid electrode as an efficient voltammetric sensor for detection of metformin: a theoretical and experimental study. Journal of the Iranian Chemical Society. 2016 Jun;13:1027-35.

65. Radi AE, Eissa SH. Electrochemical study of glimepiride and its complexation with ?-cyclodextrin. Collection of Czechoslovak Chemical Communications. 2010 Dec 1;76(1):13-25.

66. AL-TAEE AT, AL-HAFIDH AZ. Electrochemical Behavior of Valsartan, Glimepiride and Their Interaction with Each Other Using Square Wave Voltammetry. The Eurasia Proceedings of Science Technology Engineering and Mathematics. 2019 Nov 24;7:236-48.

67. Sebaiy M. M., Abdelazeem A. I., Aboulfotouh A., Rouk A. A., Mohamed A. A., Mahny A. G. (2022) Instrumental Analysis of Chloroquine and Hydroxychloroquine in Different Matrices. Curr. Res: Integr. Med. 7(2):1-8. DOI:10.37532.2022.7.2

68. Batakoushy H. A., Omar M. A., Ahmed H. M., Abdel Hamid M. A., Sebaiy M. M. (2022) Review article: Pharmacology and Analytical Chemistry Profile of Dapagliflozin, Empagliflozin andSaxagliptin. Modern App. Pharm. Pharmacol., 2(5): MAPP.000548 DOI: 10.31031/MAPP.2022.02.000548

69. Ali O. T., Elgendy K. M., Saad M. Z., Hassan W. S., Sebaiy M. M. (2021) Analytical Techniques for Determination of Albendazole, Fenbendazole, Omeprazole and Fluconazole in Pharmaceutical and Biological Samples. Int. J. Pathol. Immunol., 2(1): 1-24.

70. Lashine E. M., El-Sayed A. S., Elshahat A. K., Zaki A. R., El-Halaby A. S., Mostafa A. S., Shabaan A. K., Sobhy A. S., Abd Alsamed A. S., El-attar A. S., Farrag A. S., Sebaiy M. M. (2021) Spinal Muscle Atrophy (Types I & II & III & IV): Literature Review. Clin. Pharmacol. Toxicol. Res., 4(6): 1-6.

71. Ramadan A., Abd-Elaziz A., Ismail E. M., Maher A., Hegazy K. M., Sebaiy M. M. (2021) Review article: Pharmacological and Analytical Profile of Celecoxib. Pharm. Sci. Biomed. Anal. J., 4(1):128 https://scientificliterature.org/Pharmaceutics/Pharmaceutics-21-128.pdf

72. Elsabbagh O. I., Soror A. W., Moselhy A. Y., Elayat A. E., Hafez A. M., Saleh A. M., Nagib O. A., Khorkhash E. I., Abdelgalil E. I., Abdelmaksod E. I., Elsayed E. A., Sebaiy M. M. (2021) Literature Review on Obesity: Causes, Treatment and Correlation with Pandemic COVID-19. Pharm. Drug Regul. Affair J. (PDRAJ)., 4(1): 000124. DOI: 10.23880/pdraj-16000124

73. Ibrahim SM, Elshafiey EH, Abdulrahim ER, Azazy ER, Abd-Elghany EZ, et al. Steroids in Medicinal Chemistry: Literature Review. Academic Journal of Chemistry. 2021;6(3):69-78.

74. Ibrahim AE, Elhenawee M, Saleh H, Sebaiy MM. Overview on liquid chromatography and its greener chemistry application. Annals of Advances in Chemistry. 2021 Apr 7;5(1):004-12.

75. Abdel-Aziz L. M., Soror A. A., Hassan A. A., Ali A. S., Hafez A. A., Hemdan A. A., Sebaiy M. M. (2021) Review article: Instrumental Analysis of Chlordiazepoxide in Different Matrices. Int. Res. J. Multidiscipl. Technovat. (IRJMT)., 3(5): 1-10. https://doi.org/10.34256/irjmt2151

76. Sebaiy MM. Mini-review on Glaucoma Drugs, Timolol and Latanoprost: Mode of Action and Analytical Methods. Open J Pharma Sci. 2021;1:1-3.

77. Sebaiy MM. Analytical Review: Methods of Determination for Ledipasvir and Velpatasvir in Pharmaceutical and Biological samples. BR Nahata Smriti Sansthan International Journal of Phramaceutical Sciences & Clinical Research. 2021 Aug 12;1(2).

78. Ibrahim AE, Elhenawee M, Saleh H, Sebaiy MM. Sci Forschen.

79. Sebaiy M. M., Shanab A. G., Nasr A. K., Hosney A. E., Elsaid A. G., Ramadan A. H. (2021) Literature Review on Spectrophotometric, Chromatographic and Voltammetric Analysis of Ivermectin. Med. Anal. Chem. Int. J. (MACIJ)., 5(1): 000170. https://doi.org/10.23880/macij-16000170

80. Kumaraswamy G, Pranay K, Rajkumar M, Lalitha R. Novel stabilty indicating rp-hplc method simultaneous determination of sofosbuvir and velpatasvir in bulk and combined tablet dosage forms. Innov Int J Med Pharm Sci. 2017;2(7).

81. Abdel-Aziz LM, Sapah AA, Naser A, Abd-Elaziz A, El-Emary A, et al.. Spectroscopic, Chromatographic and Electrochemical Determination of Indomethacin in Different Matrices. European Journal of Science, Innovation and Technology. 2021 Jun 29;1(2):32-40.

82. Sebaiy MM, Farouk EM, Lotfy EM, Mokhtar EM, Abd-Elgwad EN, et al. (2021) Review article: Spectroscopic, Chromatographic and Electrochemical Analysis of Azithromycin in Different Matrices. J Drug Des Res 8(2):1084.

83. Adel E. Ibrahim, Magda Elhenawee, Hanaa Saleh, Mahmoud M. Sebaiy. “Overview on Hepatitis C, Treatment Strategy, Instrumental Analysis of Anti-HCV drugs’’. J Pharmacy and Drug Innovations, 2(2); DOI: http;//doi.org/03.2020/1.1014.

84. SARAYA RE, ELHENAWEE M, SALEH H, SEBAIY MM. Mini Review: Insights on Instrumental Analysis of Ombitasvir, Paritaprevir and Ritonavir. International Journal of Chemistry Research. 2021 Apr 1:1-4.

85. Elrefay H, Ismaiel OA, Hassan WS, Shalaby A, Fouad A, et al. Mini-Review on Various Analytical Methods for Determination of Certain Preservatives in Different Matrices. Int. J. Res. Stud. Sci., Eng. Technol.(IJRSSET). 2021;8:1-8.

86. Ibrahim A. E., Elhenawee M., Saleh H., Sebaiy M. M. (2021) Mini-review on Chromatography of Proteomics. Glob. J Chem. Sci. 1(1): 1-4.

87. Ali OT, Elgendy KM, Saad MZ, Hassan WS, Sebaiy MM. Review Article: Instrumental Analysis of Certain Azoles with Variant Anti-Infective Activity.

88. Saraya R. E., Elhenawee M., Saleh H., Sebaiy M. M. (2021) Review article on Analytical Techniques of Lamivudine Determination in Different Matrices. J. Adv. Pharm. Sci. Tech (JAPST)., 2(3): 37-46. DOI: 10.14302/issn.2328-0182.japst-20-3664

89. Scheme I. Analytical Methods for Determination of Certain Antihypertensive Drugs.

90. Sebaiy MM, Saraya RE, Elhenawee M, Saleh H. Analytical Methods for Determination of Ondansetron hydrochloride and Pantoprazole. Journal of Medical Research and Health Sciences. 2021 Feb 24;4(2):1175-81.

91. Elbaramawi SS, El-Sadek ME, Baraka MM, Abdel-Aziz LM, Sebaiy MM. Instrumental analysis of some anti-ulcer drugs in different matrices. Chemical Reports. 2020 Nov 17;2(1):156-72.

92. Elkady Y, El-Adl SM, Baraka M, Sebaiy MM. Literature Review of Analytical Methods for Determination of Triamcinolone Acetonide and Benzyl Alcohol. Novel Approaches in Drug Designing & Development. 2020;5(3):49-54.

93. Yara Elkady, Sobhy M. El-Adl, Mohamed Baraka and Mahmoud M. Sebaiy (2020) Analytical Methods for Determination of Salbutamol, Ambroxol and Fexofenadine J, Biotechnology and Bioprocessing 1(1); DOI: 10.31579/2766-2314/004

94. Ibrahim F, Sobhy M, Baraka MM, Ibrahim SM, Sebaiy MM. Analytical methods for the determination of certain antibiotics used in critically ill patients. Journal of Pharmaceutical and Biopharmaceutical Research. 2020 Jun 9;2(1):99-117.

95. Sebaiy MM, Abdellatef HE, Elhenawee MM, Elmosallamy MA, Alshuwaili MK. Review Article: Instrumental Analysis of Olopatadine Hydrochloride, Oxeladine Citrate, Amlodipine Besylate and Xipamide. Int J Analyt Bioanalyt Methods. 2020;2(010).

96. Sebaiy MM, Sm EA, Mm B, Aa H. Analytical Methods for Determination of Certain Sartans and Diuretics. J. Chem. Sci. Chem. Eng. 2020;1:11-8.

97. Sebaiy MM, Hegazy KM, Ebrahim AM, Essam FM, Amin FA, et al. Captopril and Hydrochlorothiazide: Insights on Pharmacology and Analytical Chemistry Profile. Journal of Chemistry & its Applications. 2022;1(2):1-2.

98. Elrefay H, Ismaiel OA, Hassan WS, Shalaby A, Fouad A, Sebaiy MM. Literature Review on Instrumental Analysis of Metformin Hydrochloride, Glibenclamide, Glimepiride and Pioglitazone Hydrochloride in Different Matrices. Pharmaceutical Sciences And Biomedical Analysis Journal. 2022; 4(1):130

99. Sebaiy MM, Elrefay H, Ismaiel OA, HassanWS, Shalaby A , et al. (2022) Insights on Analytical Methods for Determination of Risperidone, Levetiracetam, Sodium Valproate and Oxcarbazepine. Der Pharmacia Sinica Vol:13 No:3

100. Mahmoud M. Sebaiy, Mohamed Y . Hassaballah and Noha I. Ziedan. Topoisomerase II Inhibitor as a Potential Therapy for Severe COVID-19: Antiviral Activity and Molecular Docking Studies. Pharmaceutical Sciences And Biomedical Analysis Journal. 2022; 4(2):132

101. Sebaiy MM, Abdelmonem A, Reda A, Fathy A, Gamal A. Insights on COVID-19 Pathophysiology and Treatment. Journal of Pharmaceutical Research and Drug Safety. 2022;1:103.

102. Sebaiy MM, Hegazy KM, Ebrahim AM, Essam FM, Amin FA, et al. Captopril and Hydrochlorothiazide: Insights on Pharmacology and Analytical Chemistry Profile. Journal of Chemistry & its Applications. 2022;1(2):1-2.

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