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Abstract

Cardiovascular diseases and diabetes mellitus represent two of the most significant global health burdens, frequently coexisting and synergistically increasing morbidity and mortality. Metoprolol succinate, a cardioselective ?1 adrenergic receptor blocker, is extensively prescribed for hypertension, angina pectoris, heart failure, and arrhythmias. Empagliflozin, a sodium–glucose co transporter 2 (SGLT2) inhibitor, is widely used in the management of type 2 diabetes mellitus and has shown remarkable cardiovascular and renal protective effects beyond glycemic control. This review article provides a comprehensive overview of Metoprolol succinate and Empagliflozin, including their pharmacological actions, physicochemical properties, therapeutic applications, and reported analytical methods. Special emphasis is placed on analytical techniques such as UV spectrophotometry, high performance liquid chromatography (HPLC), high performance thin layer chromatography (HPTLC), and liquid chromatography–mass spectrometry (LC–MS/MS) used for their estimation individually and in combined dosage forms. This review aims to serve as a ready reference for researchers, analysts, and formulation scientists.

Keywords

Metoprolol succinate, Empagliflozin, heart failure, diabetes mellitus, .High Performance Liquid Chromatography, High Performance Thin Layer Chromatography, Telmisartan, Ultraviolet Spectroscopy

Introduction

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Metoprolol succinate (MET) is an antihypertensive medication that acts as a competitive beta-adrenergic receptor antagonist (Cardio selective). It exhibits membrane stabilizing effects when administered at a higher dose than that required to demonstrate antagonist property. (1)

Mechanism of Action:

Metoprolol is a beta-1-adrenergic receptor inhibitor specific to cardiac cells with negligible effect on beta-2 receptors. This inhibition decreases cardiac output by producing negative chronotropic and inotropic effects without presenting activity towards membrane stabilization nor intrinsic sympathomimetics. (2)

Empagliflozin (EMP) is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), the transporters primarily responsible for the reabsorption of glucose in the kidney. It is used clinically as an adjunct to diet and exercise, often in combination with other drug therapies for the management of type 2 diabetes mellitus.(3)

Mechanism of Action

The vast majority of glucose filtered through the glomerulus is reabsorbed within the proximal tubule, primarily via SGLT2 (sodium-glucose linked co-transporter-2) which is responsible for ~90% of the total glucose reabsorption within the kidneys. Na+/K+-ATPase on the basolateral membrane of proximal tubular cells utilize ATP to actively pump Na+ ions into the interstitium surrounding the tubule, establishing a Na+ gradient within the tubular cell. SGLT2 on the apical membrane of these cells then utilize this gradient to facilitate secondary active co-transport of both Na+ and glucose out of the filtrate, thereby reabsorbing glucose back into the blood – inhibiting this co-transport, then, allows for a marked increase in glucosuria and decrease in blood glucose levels.Empagliflozin is a potent inhibitor of renal SGLT2 transporters located in the proximal tubules of the kidneys and works to lower blood glucose levels via an increase in glucosuria. (4)

Metoprolol succinate and Empagliflozin treat different conditions, but are often used together for cardiovascular issues like heart failure, diabetes, hypertension, and post-heart attack recovery, as they complement each other's actions.

PHYSICAL AND CHEMICAL PROPERTIES

Metoprolol succinate is a white, crystalline powder, highly water-soluble, used as a beta-blocker; review articles highlight its poor micromeritic properties (flow, compressibility) and low melting point, leading to extensive research on developing sustained-release (SR) formulations using polymers (like HPMC, Carbopol) or co-crystals to improve solubility, stability, and patient compliance by reducing dosing frequency. Studies use techniques like DSC, FTIR, and XRPD to characterize these improved formulations, focusing on enhancing dissolution and bioavailability. (5)

Empagliflozin is a white to yellowish powder, practically insoluble in water but soluble in organic solvents like DMSO and ethanol, with a molecular weight of ~450.91 g/mol, chemical formula C23H27ClO7, and is a C-glycoside structure, not hygroscopic, and stable without polymorphism, serving as an SGLT2 inhibitor. (6)

                        

 

        Figure 1 Structure of Empagliflozin               Figure 2 Structure of Metoprolol succinate

Table 1 Official method for assessment of Metoprolol succinate

Sr. No.

Official

Description

Ref. No.

01

Indian Pharmacopoeia (IP-2018)

Method : Chromatography

Wavelength : 223 nm

Stationary phase : Octadecylsilane Silica (15cm x 3.9mm)

Mobile phase : Buffer : Acetonitrile (60:40)

Flow rate : 0.9 mL/min

Detection : Spectrophotometer

7

02

United States Pharmacopoeia (USP-2011)

Method : Potentiometric method

Solvent : Anhydrous acetic acid

Titrant : 0.1M Perchloric acid

1ml of 0.1M Perchloric acid ≈ 32.64mg C4H56N2O10

8

03

British Pharmacopoeia (BP-2018)

Method : Liquid Chromatography

Wavelength : 223nm

Stationary phase : Octadecylsilyl silica

Mobile phase : Sodium dodecyl sulphate : CAN (60: 40)

Flow rate : 0.9 mL/min

Detection : Spectrophotometer

9

Table 2 Reported  methods for assessment of Metoprolol succinate

Sr. No.

Author

Title

Method

Description

Ref. No.

01

Bharad VJ, et al.

 

Metoprolol succinate

Spectroscopic Method

Solvent: Water, HCl,

Methanol λmax : 222nm

Range : 5-25 µg/ml

10

02

Jain PS, et al.

Metoprolol succinate in bulk and tablet dosage form

UV- spectrophotometric method

Solvent : Water

λmax : 264 nm & 283 nm

Range : 40-200 g/ml

11

03

Dhole SM, et al.

Metoprolol succinate and Amlodipine Besylate in Their Combined Tablet Dosage Form

UV Spectrophotometric

Solvent : Methanol and Water

λmax : 221nm (MS) & 364nm(AB)

Range: 2-20 μg/mL (MS) & 1-10 μg/mL (AB)

12

04

Vora BN, et al.

Metoprolol succinate & Olmesartan medoxomil in the tablet dosage form

UV spectrophotometric method

Solvent: Methanol and water

λmax : 221 nm (MS) & 257 nm (OM)

Range: 5–25 μg/ml(M) & 4–20 μg/ml (O)

13

05

Gopika VC, et al.

Metoprolol succinate & Benidipine hydrochloride in their combined tablet dosage form

UV spectrophotometric method

Solvent: Methanol

λmax : 223nm (MS) & 237nm (BH)

Range: 3-21 µg/mL

14

06

Chabukswar AR, et al.

Metoprolol succinate & Amlodipine in Their Combined

Dosage Form

Absorption Corrected (A) & Isoabsorptive Point (B)

Solvent: Methanol

λmax : 277.017 nm and 235.62 nm

Range: 50-250μg/ml (M) & 5-25μg/ml (A)

15

07

Modi M, et al.

Metoprolol succinate & Telmisartan In Combined Pharmaceutical Formulation
  1. Derivative simultaneous equation (Vierodt’s method)
  2. 1st derivative Q-Absorbance equation
  3. ? Absorbance correction
  4.  Combination of 1st derivative dual WL

Solvent: Methanol

 λmax : 230 nm

Range: 3-20 µg/ml (METO) & 4-16 µg/ml (TEL)

16

08

Patel PB, et al.

Metoprolol succinate & Telmisartan and in tablet dosage form

Second order derivative

Solvent: Methanol

λmax : 299 nm(T) (ZCP – M) & 224nm (M) (ZCP-T)

Range: 3-15µg/ml

17

09

Shanmu gasunda ram V, Et Al.

Metoprolol succinate & Atorvastatin Using Biorelevant Dissolution Media (Fasted State Small Intestinal Fluid)

RP-HPLC

λmax : 244nm

Range: 50–250 μg/ml (MS) & 10-50µg/ml (AT)

Mobile Phase : Phosphate

buffer : Acetonitrile (35:65)

Detector : UV detection

Flow rate : 1 ml/min

Run time : 15.0 min

18

10.

Madhukar A, et al.

Metoprolol succinate in tablet dosage form

RP-HPLC

Solvent: Methanol

λmax : 225nm

Range : 25-125μg/mL

Column : C18

Detector : PDA

Flow rate : 1ml/min

Run time : 4.8 min

19

11.

Yska JP, et al.

Metoprolol succinate & α-hydroxy metoprolol in human serum, For application in pharmacokinetics

High- resolution accurate mass LC-MS

Solvent: Methanol

Range : 5 - 250 µg/L

Mobile Phase : Water: Acetonitrile (15 : 85, v/v)

Detector: Exactive® Orbitrap

Run time: 15 min

20

12.

Agrawal S, et al.

Metoprolol succinate & Trimetazidine Hydrochloride

Simultaneous Estimation using HPTLC

Solvent : n-butanol : Water : Methanol : Ammonia

λmax : 213nm

Range : 500-2500 ng band-1 (TH) & 500-2500 ng band-1 (MS)

Mobile Phase : n-butanol : Water : Methanol: Ammonia (8.5 : 0.1 : 0.1: 0.85, v/v)

Stationary Phase : Pre- coated silica gel G 60 F254 TLC plate

21

13.

Rao DS, et al.

Metoprolol succinate & Cilnidipine Dissolution Test

RP-HPLC

Solvent: OPA: Methanol (70:30)

λmax : 285 nm

Range: 50% to 150%

Mobile Phase : OPA: Methanol (70 : 30)

Column : ELIPSE C18

Flow rate: 1.0mL/min

Run time: 2.59 (M) & 4 min (CD)

22

14.

Corina MS, et al

Metoprolol succinate & Bisoprolol

MS, GC coupled with GC, HPLC

-

23

15.

Saravanan G, et al

Metoprolol succinate & Cilnidipine

Stability Indicating RP-HPLC

Solvent: Water : Acetonitrile (50 : 50)

λmax : 230 nm

Mobile Phase : Acetonitrile :

Sod. Dihydrogen ortho phosphate buffer (65 : 35)

Column: STD kromasil 150 C18

Flow rate: 0.8ml/min

Run time: 2 min(M)& 3min

24

16.

Kumar CH, et al

Metoprolol succinate

stability indicating RP-HPLC

Solvent: Methanol

λmax : 223 nm

Range: 20-200µg/ml

Mobile Phase : Buffer (PH- 6.8) : Methanol : Acetonitrile (600 : 50 : 350)

Detector: PDA

Run time: 11 min

25

17.

Sheikh KS, et al.

Metoprolol succinate & Telmisartan in extended release tablets

Stress degradation studies by a validated stability indicating RP- HPLC method

Solvent: Methanol

λmax : 222 nm

Range: 80–2 μg/mL (TS) & 100-4 μg/ mL (MS)

Mobile Phase : 0.05 M Sodium dihydrogen Phosphate buffer pH 3.0 : Acetonitrile ( 75 : 25 v/v)

Column: Inertsil ODS 3V Detector: PDA

Flow rate: 1ml/min

26

18.

Jain N, et al.

Metoprolol succinate & Telmisartan

UV Spectrophotometry & RP- HPLC

Solvent: 50% methanol

λmax : 240.5 nm(MS) and

237.5 nm(TEL)

Chromatogram(225nm) Range : 5-25 μg mL (MS) & 8-40 μg mL(TEL)

Mobile Phase : Methanol: Acetonitrile : Phosphate buffer (pH-5) 35:35:30 v/v/v Column: C18

Flow rate: 1ml/min

27

19.

Shrivastav PS, et al.

Metoprolol succinate in human plasma

chiral LC- ESI-MS/MS

Range: 0.500-500 ng/mL Mobile Phase : 15 mM Ammonium acetate : Water : 0.1% (v/v), Diethyl amine : Acetonitrile (50:50)

Column: Lux amylose -2

Run time: 7 min

28

20.

Kashya p R, et al.

Metoprolol succinate & Chlorthalidon in Bulk and Dosage Form

HPLC

Solvent : Buffer : Methanol : Acetonitrile λmax : 223nm

Range : 5-15 µg/ml (C) & 20-60 µg/ml (MS)

Mobile Phase : Buffer pH

4.5: Methanol : Acetonitrile (50:25:25)

Column : C18 Detector : LC 100 UV

Flow rate : 1.0 ml/min

29

21.

Ravisankar P, et al.

Metoprolol succinate & Atenolol, Hydrochlorothiazide, Amlodipine and Nebivolol

RP HPLC

Solvent: Phosphate buffer:

Acetonitrile

λmax : 235nm

Range : 2-10µg/ml (MS) Mobile Phase : 10 mM Phosphate buffer (pH3.0) : Acetonitrile (50:50 v/v) Flow rate: 1ml/min

Run time: 2min

30

22.

Nalluri BN, et al.

Metoprolol succinate & Telmisartan In Bulk And Pharmaceutic al Dosage Forms

RP-HPLC

Solvent: Methanol

λmax : 230nm

Range : 5-25 µg/mL (MS) & 2-10µg/mL (TEL)

Mobile Phase : 15mM Ammonium acetate (pH 6.5): Acetonitrile (58:42)

Column: C18

Detector: SPD-M20A PDA

Run time: 3.9 min(M), 5.3 min(T)

31

23.

Thakkar NM, et al.

Metoprolol succinate & Olmesartan Medoxomil in pharmaceutical dosage form

Stability indicating RP-HPLC method for simultaneous estimation

Solvent : Acetonitrile : Water

λmax : 220nm

Range : 5-35 μg/ml

Mobile Phase : 0.05%

Trifluoro acetic acid (TFA): Acetonitrile (70 : 30 v/v)

Column: YMC-Pack CN

Detector: UV/VIS PDA

Flow rate: 1ml/min

Run time: 7 min

32

24.

Rao LA, et al.

Metoprolol succinate & Amlodipine In Bulk Drug And Pharmaceutical Formulations

Stability Indicating HPLC

Solvent : Buffer, Acetonitrile λmax : 237nm

Range : 10-50 μg/mL (AD) & 40-200μg/mL (M)

Mobile Phase : Acetonitrile : Potassium dihydrogen phosphate buffer adjusted to pH 3.0 (50:50, v/v)

Column: RP C18 ace-EPS Detector: UV

Flow rate: 0.6ml/min

33

25.

Baldania SL, et al

Metoprolol succinate & Olmesartan Medoxomilin Pharmaceutical Formulation

Thin-Layer Chromatographic- Densitometric

Solvent : Methanol

λmax : 224nm

Range :1000–2250 ηg per spot (MS) & 800–1800 ηg per spot (OM)

Mobile Phase : Methanol : Ethyl acetate : Toluene : Glacial acetic acid (2.5 : 3 : 4.5 : 0.3V/V)

Stationary Phase : silica gel

G 60 F254

34

26.

Jain N, et al.

Metoprolol succinate & Telmisartan in Bulk Drug and Their Dosage Forms

RP-HPLC

Solvent : Acetonitrile : Methanol : Phosphate buffer

 λmax : 225nm

Range : 5-25 µg/ml (M) & 8-40 µg/ml (T)

Mobile Phase : Acetonitrile : Methanol : Phosphate buffer

pH-5 (35:35:30 v/v/v)

Column : Prontosil C18 Flow rate : 1ml/min

Run time : 2.57 min (M) &

4.68 min (T)

35

27.

Raval M, et al.

Metoprolol succinate & Olmesartan Medoxomil in Tablet Dosage

RP-HPLC

Solvent: Methanol: Water: CAN

λmax : 231nm

Range: 5-30µg/ml (M) & 2-12 µg/ml (OM)

Mobile Phase : Methanol: Water: Acetonitrile (70: 20 : 10)

Column: Hibar 250-4.6 C18

Flow rate: 1ml/min

Run time: 2.1 min (MS) 3.0

min (OM)

36

28.

Deshpande PB, et al.

Metoprolol succinate & Olmesartan in Combined Capsule Dosage Form

HPTLC

Solvent : Methanol

λmax : 225nm

Range : 250-2500 ng band -1 (MS) & 100-1000 ng band -1

Mobile Phase : n- butanol : Methanol (6:3, v/v)

37

29.

 Nawale PS, et al.

Metoprolol succinate & Telmisartan in Pharmaceutical Formulation

(1) Normal (2) Reversed- Phase HPTLC

Solvent: Methanol

λmax : 242nm

Mobile Phase : (1) Toluene : Propanol : Methanol : triethylamine (8:1:1:0.5 v/v)

(2) Methanol: Water : Triethylamine (6:4:0.5 v/v)

Column:(1) silica gel 60F254S (2) Aluminium coated with RP-18 silica gel 60 F254S

38

30.

Patel MM, et al.

Metoprolol succinate & Olmesartan Medoxomil in Pharmaceutical Dosage Form

RP-HPLC

Solvent : Methanol

λmax : 220nm

Mobile Phase : Buffer (2 ml O-phosphoric acid in 2000 ml milli-Q Water) & Acetonitrile 50:50 (v/v)

Column : inertsil ODS 3V Detector : PDA

Flow rate : 1min/min Run time: 1.6 min(M) & 2.4

min (OM)

39

31.

Phale MD, et al.

Metoprolol succinate from Bulk Drugs

RP HPLC

Solvent: Methanol

 λmax : 254nm

Column: RP Spherisorb C18 Flow rate: 1ml/min

Run time: 5min

40

32.

Ghosh SK, et al.

Metoprolol succinate & Hydrochlorothiazide in a Tablet Formulation

RP- HPLC

Solvent : 50mM di-sodium hydrogen phosphate : Methanol : Acetonitrile

λmax : 222nm

Range : 2.0, 4.0, 8.0, 16.0, 32.0 ppm

Mobile Phase : 50mM di- sod. hydrogen phosphate: Methanol : Acetonitrile

41

Table 3 Reported  methods for assessment of Empagliflozin

Sr.

No.

Author

Title

Description

Ref

No
  1.  

Gaikwad, Asmita V., and Preeti Khulbe

HPLC Method Development for the Estimation of Empagliflozin in Bulk and Pharmaceutical Formulation

Mobile Phase: Water: CAN

(55:45 v/v)

Column: Waters C-18, 100 x 4.6 mm, 2.7 um, Poroshell 120 EC-C18

Detection: 225nm

42
  1.  

Sushil D. Patil, Sayali K. Chaure, Maswood Ahmed Hafizur Rahman, Prajkta U. Varpe, Sanjay Kshirsagar

Development and Validation of Simple UV- Spectrophotometric Method for the Determination of Empagliflozin

Solvent: water: methanol (9.0:1.0)

Λmax: 224 nm

 

43
  1.  

Manojkumar K. Munde, Nilesh S. Kulkarni, Rahul H. Khiste, Dhanya B. Sen

Development and Validation of Novel Analytical Method for Empagliflozin and Metformin Hydrochloride in Bulk and Pharmaceutical Dosage Form by Four Different Simultaneous Estimation Approaches using UV Spectroscopy

Detection WL: 224 and 232 nm

 

44
  1.  

Vaishali M. Badgujar, Pritam S. Jain

Stability-Indicating RP-HPLC Method Development for the

Determination of Empagliflozin

Agilent C18 column (5µm; 4.6 x 250 mm)

Mobile phase: methanol/ 0.05% pH 3.3 acetic acid (75:25)

Stability: Oxidative stress and exposure to water caused relatively higher degradation

45
  1.  

Madure V, Barge V.

Analytical Method Development and Validation of RP-HPLC Method For Estimation of Empagliflozin in Bulk and Pharmaceutical Dosage Form.

Mobile phase: mixture of 0.1 % Trifluoroacetic acid in Water and Methanol

Column: Phenomenex C-18, 250 mm X 4.6 mm, 5 µm

46
  1.  

Joanna Wittckind Manoel

Determination of empagliflozin in the presence of its organic impurities and identification of two degradation products using UHPLC-QTOF/MS

Instrument:  UHPLC equipment (Shimadzu-Nexera x2), Zorbax Eclipse Plus

Column: C18 column (2.1 × 50 mm, 1.8 µm)

Temperature: 35 °C

47
  1.  

Juveriya Fatima Siddiqui

Analytical Method Development and Validation for Simultaneous Estimation of Empagliflozin and Linagliptin in Bulk Drug and in Pharmaceutical Dosage Formulation by HPLC

Column: waters acquity C18 (100 X 2.1mm id)

Retention time: 1.320 and 2.343 min

Wavelength: 270nm

 

48
  1.  

Yogeshwari Jambhulkar1, Nitu Madan and Pratik Mate

EMPAGLIFLOZIN: RP-HPLC BASED ANALYTICAL METHOD DEVELOPMENT AND VALIDATION

Column: C18

Mobile phase: 0.1% trifluoroacetic acid: acetonitrile 70:30 (v/v) pH 4.8

49
  1.  

Avinash C, Gandhimathi R.

RP-HPLC Method Development and Validation for an Estimation of Empagliflozin from Bulk and Pharmaceutical Dosage Form

Column: Agilent Eclipse XDE C-18 (4.6 mm x 250 mm, 5.0 m particle size)

Mobile phase: 0.1 M TEA pH 5.5 corrected by methanol and OPA in a proportion of 4:96 percent v/v

Wavelength: 270 nm

50
  1.  

Pathak, S., Mishra, P

Stability-indicating HPLC-DAD method for the determination of empagliflozin

Detector: DAD

Mobile phase: methanol/ acetonitrile/ 0.1% OPA (75:20:5)

Retention time: 2.54 min

51
  1.  

N. Padmaja and G. Veerabhadram

Development and validation of analytical method for Simultaneous estimation of Empagliflozin and Linagliptin in bulk drugs and combined dosage forms using UV-visible spectroscopy

Vierodt’s Method WL: 233nm and 277nm

concentration range: 5-15µg/ml

Solvent: Methanol

52
  1.  

A. Raja Reddy, J.Lavanya, T. Rama Rao , B. Revathi

analytical method development and validation for simultaneous estimation of metformin and empagliflozin in bulk and pharmaceutical dosage form by RP-HPLC

Column: C18 150 mm I.D × 4.6 mm,5 µm

Mobile phase: 0.1N Potassium dihydrogen phosphate: Acetonitrile (50:50)

Wavelength: 260nm

53
  1.  

Abhijeet N. Raut, Shailesh G. Jawarkar, Vaibhav S. Khodke, Vivek A. Khole

method development, validation by simultaneous estimation of empagliflozin and linagliptin by RP-HPLC method

Column: C18 (Equisil BDS) column (4.6 × 250 mm) 5μ

Mobile phase: (40:60 v/v) methanol: water

Instrument: SHIMADZU-HPLC system

Pump -HPD 20A

Detector - UV detector

Software - UV Probe

54
  1.  

Chandni Chandarana, Aarti Panchal, Vishal Modi

RP-HPLC Method Validation for Estimation of related Substances of Empagliflozin

Mobile phase: Water:ACN

Column: Phenomenex (Kinetex) C18 stationary phase (250mm × 4.6mm, particle size 5µm)

Detection : 240nm

55
  1.  

Dr. K M Khairul Alam1,* Tanbin Jahan Ferdousy

Development and Validation of an RP-HPLC Method for Determination of Empagliflozin in Empagliflozin Tablet

Column: C18 (250 mm × 4.6 mm, 5 µm particle size)

Mobile phase: 0.01 M NaH2PO4 (as buffer) and acetonitrile

WL: 210nm

56
  1.  

Mounika P Siridevi, Hemant T Kumar, Srinivasa Y Rao, Vara Prasad K Rao.

RP-HPLC Method for Quantification of Empagliflozin in Pharmaceutical Formulation.

Column: C18G (250 x 4.6 mm i.d.,5µ)

Mobile phase: methanol and water in the ratio of 70:30 % v/v

WL: 233nm

57

Table 4 Reported  methods for assessment of Metoprolol succinate and Empagliflozin in combination

Sr.

No.

Author

Title

Description

Ref.

No

1

Heena Ninama, Shaileshkumar K. Koradia

RP-HPLC Based Concurrent Analysis of Empagliflozin and Metoprolol Succinate in a Novel Pharmaceutical Combination Tablet

Column: Shim-pack ODS C18 column (250 mm × 4.6 mm I.D., 5 µm)

Mobile Phase: potassium dihydrogen phosphate buffer (pH 3.5) methanol, and acetonitrile in a 45:20:35 % (v/v/v)

WL: 222nm

Retention time: 8.217 min

58

2

Heena Ninama, Shaileshkumar K Koradia

Greenness assessment and stability-indicating HPTLC method for the concurrent analysis of empagliflozin and metoprolol succinate in a novel combined oral formulation

Stationary Phase: HPTLC silica gel 60 F254 plates

Mobile Phase: chloroform: methanol: toluene (3.0:2.5:4.5, v/v/v)

Detection: 222nm

59

3

Vandit Patel , Riddhi Trivedi, Munshi Mahammed Tanzil , Deepa R. Patel

Stability Indicating Method Development and Validation of Metoprolol Succinate and Empagliflozin by RP-HPLC in Synthetic Mixture

Column: C18 (250 mm × 4.6 mm, 5 μm)

Mobile phase: acetonitrile and phosphate buffer (pH 4.0) in the ratio of 60:40 v/v

Detection: 225nm

60
 

CONCLUSION:

This review article presents the Physicochemical properties and Pharmacological actions of Metoprolol succinate and Empagliflozin. The presented review gives information about the various methods reported in the literature for determining Metoprolol succinate and Empagliflozin, including official pharmacopeial assay methods.

This review concluded that different analytical methods are reported for the estimation of Metoprolol succinate and Empagliflozin individually and other combinations like UV Spectroscopy, HPLC, HPTLC, and LC-MS. Hence, all methods were simple, accurate, precise, and reproducible. The Literature review focuses on various UV methods reported for Metoprolol succinate and Empagliflozin in fixed-dose combinations. This review will help develop the analytical methods for this new combination and give knowledge about both drugs' characteristics.

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  14. Gopika VC and Remi SL, “Validated UV spectrophotometric method for simultaneous estimation of metoprolol succinate and benidipine hydrochloride in their combined tablet dosage form”, Asian J. Pharm. Hea. Sci. 2018, 8, 1968-1975.
  15. Chabukswar AR, Mohokar MN, Choudhari VP, Sharma SN, Tambe SD and Pagare BD, “Absorption Corrected Method & Isoabsorptive Point Method for Simultaneous Estimation of Metoprolol and Amlodipine in Their Combined Dosage Form”, IJPSDR. 2012, 240-244.
  16. Modi M, Shah R and Mashru RC, “Development And Validation Of Spectrophotometric Methods For Simultaneous Estimation Of Metoprolol Succinate And Telmisartan In Combined Pharmaceutical Formulation”, IJPSR. 2012, 3(5), 1348-1354.
  17. Patel PB, Marolia BP, Shah SA and Shah DR, “Second order derivative spectrophotometric method for simultaneous estimation of Telmisartan and Metoprolol in tablet dosage form”, IRJP. 2012, 3(5), 259-262.
  18. Shanmugasundaram P and Kamarapu SK, “Method Development And Validation For The Simultaneous Determination Of Metoprolol And Atorvastatin By Reversed-Phase High-Performance Liquid Chromatography In Its Bulk And Pharmaceutical Tablet Dosage Form Using Biorelevant Dissolution Media (Fasted State Small Intestinal Fluid)”, Asian J Pharm Clin Res. 2018,11(4), 2018, 1-8.
  19. Guguloth R, Madhukar A, Umadevi G, Lalitha T, Ravinder A, “Analytical Method Development And Validation For The Determination Of Metoprolol Succinate In Tablet Dosage Form By Rp-Hplc Techniques”, J. Sci. Res. Pharm. 2016, 5(6), 74-77.
  20. Yska JP, Hommema G, Koopmans S, Wilffert B and Roon NV, “A validated high-resolution accurate mass LC-MS assay for quantitative determination of metoprolol and α-hydroxymetoprolol in human serum for application in pharmacokinetics”, Journal Of Applied Bioanalysis. 2017, 49-57.
  21. Agrawal S, Gurjar P and katheriya B, “Analytical Method Development and Validation for Simultaneous Estimation of Trimetazidine Hydrochloride and Metoprolol Succinate Using HPTLC”, 2019, 15(3), 243-250.
  22. Rao DS, Venkateswarlu T and Rama Krishna G, “Development and Validation Of Hplc Method Of Dissolution Test For Metoprolol Succinate And Cilnidipine”, IJPCBS. 2015, 5(4), 971-981.
  23. Corina MS, Hancianu M, Agoroaei L and Butnaru E, “Preparation of Biological Samples Containing Metoprolol and Bisoprolol for Applying Methods for Quantitative Analysis”, Acta Medica Marisiensis. 2015, 61(4), 356-360.
  24. Saravanan G, Naga PN, and Visagaperumal D, “Development and validation of stability indicating RP-HPLC method for the simultaneous estimation of Metoprolol succinate and Cilnidipine in bulk and pharmaceutical dosage form”, Int J Pharm Pharm Sci. 2015, 7, 150-154.
  25. Kumar CH, Mannuri S, Kuchana V and Kannappan N, “Development and validation of a stability indicating RP-HPLC method for determination of metoprolol succinate in pharmaceutical dosage forms”, Der Pharmacia Sinica. 2014, 5(6), 69-78.
  26. Shaikh KA, Patil AT, Stress degradation studies of Telmisartan and Metoprolol extended release tablets by a validated stability indicating reverse phase-high performance liquid chromatography method”, Drug Dev Ther. 2014, 5, 158-63.
  27. Jain N, Sharma BK, Jain R, Jain DK and Jain S, “RP-HPLC Method Development and Validation for Quantitative Estimation of Metoprolol Succinate and Telmisartan in Bulk Drug and Their Dosage Forms”, J Pharm Biomed Sci. 2012, 24 (24), 102-106.
  28. Sharma P, Contractor P, Guttikar S, Patel DP and Shrivastav PS, “Development of a sensitive and rapid method for quantitation of (S)- (-)- and (R)- (+)- Metoprolol in human plasma by Chiral LC –ESI-MS/MS”, Journal of Pharmaceutical Analysis. 2014, 4(1), 63-79.
  29. Kashyap R and Srinivasa U, “Development And Validation Of Hplc Method For The Simultaneous Estimation Of Chlorthalidon And Metoprolol Succinate In Bulk And Dosage Form”, IJPDA. 2013, 1, 1-14.
  30. Ravisankar P, Rao GD, Chaitanya MK, Devadasu CH and Babu PS, “Rapid Separation of Five Anti-Hypertensive Agents - Atenolol, Metoprolol, Hydrochlorothiazide, Amlodipine and Nebivolol: Application to Estimation of Metoprolol Succinate in Tablet Dosage Form”, J. Chem. Pharm. Res. 2013, 5(7), 215-228.
  31. Nallur BN, Bharathi DM, “Simultaneous Estimation Of Metoprolol Succinate And Telmisartan In Bulk And Pharmaceutical Dosage Forms By Rp-Hplc - Pda Method”, Int. J. Pharm. Sci. 2012, 16(2), 111-115
  32. Thakker NM, Panchal HB, Rakholiya RD, Choudhari PV, and Kuchekar SB, “Development and validation of a stability indicating RP-HPLC method for simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage form”, Pharm Methods. 2012, 79-85.
  33. Varma D, Rao LA and Dinda SC, “Validated Stability Indicating Hplc Method For Simultaneous Determination Of Amlodipine And Metoprolol In Bulk Drug And Pharmaceutical Formulations”, IJRPC. 2012, 2(3), 876-884.
  34. Baldania SL ,Parmar AB ,Bhatt KK, Shah DA and Chhalotiya UK, “Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Pharmaceutical Formulation by Thin-Layer ChromatographicDensitometric Method”, ISRN Analytical Chemistry. 2012.
  35. Jain N, Sharma BK, Jain R, Jain DK and Jain S, “RP-HPLC Method Development and Validation for Quantitative Estimation of Metoprolol Succinate and Telmisartan in Bulk Drug and Their Dosage Forms”, J Pharm Biomed Sci. 2012, 24 (24), 102-106.
  36. Raval M, ChikhaliaJ, Gosai M and Thumar K, “Method Development and Validation for Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Tablet Dosage Form by RP-HPLC”, Inventi Rapid: Pharm Ana & Qual Assur. 2012, 3, 1-6.
  37. Deshpande PB, Bhavnani VS, Gandhi SV, Pawar P and Gaikwad AK, “High Performance Thin Layer Chromatographic Determination of Metoprolol Succinate and Olmesartan in Combined Capsule Dosage Form”, Research J. Pharm. and Tech. 2012, 5(11), 1461-1464.
  38. Nawale PS, Shirkhedkar AA, Surana SJ and Patil AS, “Normal and ReversedPhase HPTLC Methods for Simultaneous Estimation of Telmisartan and Metoprolol Succinate in Pharmaceutical Formulation”, ISRN Analytical Chemistry. 2011, 1-6.
  39. Patel MM and Patel DD, “Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Pharmaceutical Dosage Form by RP-HPLC”, J Chromat Separation Techniq. 2012, 3, 8.
  40. Phale MD and Hamrapurkar PD, “A Validated and Simplified RP-HPLC of Metoprolol Succinate from Bulk Drugs”, Asian J. Research Chem. 2009, 2(2), 119 – 122.
  41. Singh B, Patel DK and Ghosh SK, “Development of Reverse-Phase HPLC Method for Simultaneous Analysis of Metoprolol Succinate and Hydrochlorothiazide in a Tablet Formulation”, Trop J Pharm Res. 2009, 8 (6), 539.
  42. Gaikwad AV, Khulbe P. HPLC Method Development for the Estimation of Empagliflozin in Bulk and Pharmaceutical Formulation. J. Pharm. Res. Int. [Internet]. 2022; 34(23B):22-31.  https://journaljpri.com/index.php/JPRI/article/view/6069
  43. Sushil D. Patil, Sayali K. Chaure, Maswood Ahmed Hafizur Rahman, Prajkta U. Varpe, Sanjay Kshirsagar.. Development and Validation of Simple UV- Spectrophotometric Method for the Determination of Empagliflozin. Asian J. Pharm. Ana. 2017; 7(1): 18-22. doi: 10.5958/2231-5675.2017.00004.7
  44. Manojkumar K. Munde, Nilesh S. Kulkarni, Rahul H. Khiste, Dhanya B. Sen. Development and Validation of Novel Analytical Method for Empagliflozin and Metformin Hydrochloride in Bulk and Pharmaceutical Dosage Form by Four Different Simultaneous Estimation Approaches using UV Spectroscopy. Research J. Pharm. and Tech 2020; 13(3):1236-1242. doi: 10.5958/0974-360X.2020.00228.0
  45. Vaishali M. Badgujar, Pritam S. Jain, Stability-Indicating RP-HPLC Method Development for the Determination of Empagliflozin, Asian Journal of Pharmaceutics. 2024, 18 (4): 1223
  46. Madure V, Barge V. Analytical Method Development and Validation of RP-HPLC Method For Estimation of Empagliflozin in Bulk and Pharmaceutical Dosage Form. J Neonatal Surg. 2025 Jul. 18[16];14(32S):5704-15. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/8360
  47. Joanna Wittckind Manoel, Determination of empagliflozin in the presence of its organic impurities and identification of two degradation products using UHPLC-QTOF/MS, Microchemical Journal. 161, 2021: 105795
  48. Siddiqui et al. Analytical Method Development and Validation for Simultaneous Estimation of Empagliflozin and Linagliptin in Bulk Drug and in Pharmaceutical Dosage Formulation by HPLC, Int. J. Pharm. Sci. Rev. Res., 81(1), 2023; 25, Pages: 147-151
  49. Jambhulkar1 Y et al. EMPAGLIFLOZIN: RP-HPLC based analytical method development and validation, ejpmr, 2024, 11(12), 291-297.
  50. Rahul S, Kumar BP and Avinash HR: Empagliflozin: a review on analytical and bio-analytical methods. Int J Pharm Sci & Res 2020; 11(9): 4144-51. doi: 10.13040/IJPSR.0975-8232.11(9).4144-51.
  51. Pathak, S., Mishra, P. Stability-indicating HPLC-DAD method for the determination of empagliflozin. Futur J Pharm Sci 7, 181 (2021). https://doi.org/10.1186/s43094-021-00329-w
  52. N. Padmaja and G. Veerabhadram, Development and validation of analytical method for Simultaneous estimation of Empagliflozin and Linagliptin in bulk drugs and combined dosage forms using UV-visible spectroscopy, Der Pharmacia Lettre, 2015, 7 (12):306-312.
  53. A. RAJA REDDY , J.LAVANYA , T. RAMA RAO , B. REVATHI, Analytical Method Development And Validation For Simultaneous Estimation Of Metformin And Empagliflozin in Bulk and Pharmaceutical Dosage Form By RP-HPLC, YMER. 21(11): 158-1869.
  54. Abhijeet N. Raut et al. Method development, validation by simultaneous estimation of Empagliflozin and Linagliptin by RP-HPLC Method. J Pharm Sci Innov. 2020;9(1):1-4. http://dx.doi.org/10.7897/2277-4572.091160
  55. Chandni Chandarana, Aarti Panchal, Vishal Modi. RP-HPLC Method Validation for Estimation of related Substances of Empagliflozin. Research Journal of Pharmacy and Technology. 2024; 17(10):5041-5. doi: 10.52711/0974-360X.2024.00775
  56. Dr. K M Khairul Alam1,* Tanbin Jahan Ferdousy, Development and Validation of an RP-HPLC Method for Determination of Empagliflozin in Empagliflozin Tablet, IJISRT. 8(5), 2023
  57. Mounika P Siridevi, Hemant T Kumar, Srinivasa Y Rao, Vara Prasad K Rao. RP-HPLC Method for Quantification of Empagliflozin in Pharmaceutical Formulation. Asian J. Pharm. Tech. 2019; 9(3):208-211. doi: 10.5958/2231-5713.2019.00035.7
  58. Heena Ninama, Shaileshkumar K. Koradia, Greenness assessment and stability-indicating HPTLC method for the concurrent analysis of empagliflozin and metoprolol succinate in a novel combined oral formulation, Drug Development and Industrial Pharmacy, 10.1080/03639045.2025.2594131, (1-14), (2025).
  59. Ninama H, Koradia SK. Greenness assessment and stability-indicating HPTLC method for the concurrent analysis of empagliflozin and metoprolol succinate in a novel combined oral formulation. Drug Dev Ind Pharm. 2025 Dec 4:1-14. doi: 10.1080/03639045.2025.2594131.
  60. Vandit Patel , Riddhi Trivedi , Munshi Mahammed Tanzil , Deepa R. Patel. Stability Indicating Method Development and Validation of Metoprolol Succinate and Empagliflozin by RP-HPLC in Synthetic Mixture, IJRASET. Volume 13 Issue XI, 2025.

Reference

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  10. Jadhav RS and Bharad VJ, “Analytical Method Development and Validation of Spectroscopic Method for Estimation of Metoprolol Succinate”, Der Pharmacia Lettre. 2017, 9 (6), 285-297.
  11. Jain PS, Dhakad DH, and Surana SJ, “Quantitative determination of metoptolol succinate using area under curve UV- spctrophotometric method in bulk and tablet dosage form”, ACAIJ. 2014, 14(1), 28-31.
  12.  Dhole SM, Chaple DR and Harde MT, “Validated UV Spectrophotometric Method for Simultaneous Estimation of Metoprolol Succinate and Amlodipine Besylate in Their Combined Tablet Dosage Form”, International Journal of Analytical and Bioanalytical Chemistry. 2013, 3(3), 82-85.
  13. Vora BN, Parmar RR, Nayak PP, and Shah DA, “Development and validation of the simultaneous UV spectrophotometric method for estimation of metoprolol succinate and olmesartan medoxomil in the tablet dosage form”, Pharm Methods. 2012, 3(1), 44–47.
  14. Gopika VC and Remi SL, “Validated UV spectrophotometric method for simultaneous estimation of metoprolol succinate and benidipine hydrochloride in their combined tablet dosage form”, Asian J. Pharm. Hea. Sci. 2018, 8, 1968-1975.
  15. Chabukswar AR, Mohokar MN, Choudhari VP, Sharma SN, Tambe SD and Pagare BD, “Absorption Corrected Method & Isoabsorptive Point Method for Simultaneous Estimation of Metoprolol and Amlodipine in Their Combined Dosage Form”, IJPSDR. 2012, 240-244.
  16. Modi M, Shah R and Mashru RC, “Development And Validation Of Spectrophotometric Methods For Simultaneous Estimation Of Metoprolol Succinate And Telmisartan In Combined Pharmaceutical Formulation”, IJPSR. 2012, 3(5), 1348-1354.
  17. Patel PB, Marolia BP, Shah SA and Shah DR, “Second order derivative spectrophotometric method for simultaneous estimation of Telmisartan and Metoprolol in tablet dosage form”, IRJP. 2012, 3(5), 259-262.
  18. Shanmugasundaram P and Kamarapu SK, “Method Development And Validation For The Simultaneous Determination Of Metoprolol And Atorvastatin By Reversed-Phase High-Performance Liquid Chromatography In Its Bulk And Pharmaceutical Tablet Dosage Form Using Biorelevant Dissolution Media (Fasted State Small Intestinal Fluid)”, Asian J Pharm Clin Res. 2018,11(4), 2018, 1-8.
  19. Guguloth R, Madhukar A, Umadevi G, Lalitha T, Ravinder A, “Analytical Method Development And Validation For The Determination Of Metoprolol Succinate In Tablet Dosage Form By Rp-Hplc Techniques”, J. Sci. Res. Pharm. 2016, 5(6), 74-77.
  20. Yska JP, Hommema G, Koopmans S, Wilffert B and Roon NV, “A validated high-resolution accurate mass LC-MS assay for quantitative determination of metoprolol and α-hydroxymetoprolol in human serum for application in pharmacokinetics”, Journal Of Applied Bioanalysis. 2017, 49-57.
  21. Agrawal S, Gurjar P and katheriya B, “Analytical Method Development and Validation for Simultaneous Estimation of Trimetazidine Hydrochloride and Metoprolol Succinate Using HPTLC”, 2019, 15(3), 243-250.
  22. Rao DS, Venkateswarlu T and Rama Krishna G, “Development and Validation Of Hplc Method Of Dissolution Test For Metoprolol Succinate And Cilnidipine”, IJPCBS. 2015, 5(4), 971-981.
  23. Corina MS, Hancianu M, Agoroaei L and Butnaru E, “Preparation of Biological Samples Containing Metoprolol and Bisoprolol for Applying Methods for Quantitative Analysis”, Acta Medica Marisiensis. 2015, 61(4), 356-360.
  24. Saravanan G, Naga PN, and Visagaperumal D, “Development and validation of stability indicating RP-HPLC method for the simultaneous estimation of Metoprolol succinate and Cilnidipine in bulk and pharmaceutical dosage form”, Int J Pharm Pharm Sci. 2015, 7, 150-154.
  25. Kumar CH, Mannuri S, Kuchana V and Kannappan N, “Development and validation of a stability indicating RP-HPLC method for determination of metoprolol succinate in pharmaceutical dosage forms”, Der Pharmacia Sinica. 2014, 5(6), 69-78.
  26. Shaikh KA, Patil AT, Stress degradation studies of Telmisartan and Metoprolol extended release tablets by a validated stability indicating reverse phase-high performance liquid chromatography method”, Drug Dev Ther. 2014, 5, 158-63.
  27. Jain N, Sharma BK, Jain R, Jain DK and Jain S, “RP-HPLC Method Development and Validation for Quantitative Estimation of Metoprolol Succinate and Telmisartan in Bulk Drug and Their Dosage Forms”, J Pharm Biomed Sci. 2012, 24 (24), 102-106.
  28. Sharma P, Contractor P, Guttikar S, Patel DP and Shrivastav PS, “Development of a sensitive and rapid method for quantitation of (S)- (-)- and (R)- (+)- Metoprolol in human plasma by Chiral LC –ESI-MS/MS”, Journal of Pharmaceutical Analysis. 2014, 4(1), 63-79.
  29. Kashyap R and Srinivasa U, “Development And Validation Of Hplc Method For The Simultaneous Estimation Of Chlorthalidon And Metoprolol Succinate In Bulk And Dosage Form”, IJPDA. 2013, 1, 1-14.
  30. Ravisankar P, Rao GD, Chaitanya MK, Devadasu CH and Babu PS, “Rapid Separation of Five Anti-Hypertensive Agents - Atenolol, Metoprolol, Hydrochlorothiazide, Amlodipine and Nebivolol: Application to Estimation of Metoprolol Succinate in Tablet Dosage Form”, J. Chem. Pharm. Res. 2013, 5(7), 215-228.
  31. Nallur BN, Bharathi DM, “Simultaneous Estimation Of Metoprolol Succinate And Telmisartan In Bulk And Pharmaceutical Dosage Forms By Rp-Hplc - Pda Method”, Int. J. Pharm. Sci. 2012, 16(2), 111-115
  32. Thakker NM, Panchal HB, Rakholiya RD, Choudhari PV, and Kuchekar SB, “Development and validation of a stability indicating RP-HPLC method for simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage form”, Pharm Methods. 2012, 79-85.
  33. Varma D, Rao LA and Dinda SC, “Validated Stability Indicating Hplc Method For Simultaneous Determination Of Amlodipine And Metoprolol In Bulk Drug And Pharmaceutical Formulations”, IJRPC. 2012, 2(3), 876-884.
  34. Baldania SL ,Parmar AB ,Bhatt KK, Shah DA and Chhalotiya UK, “Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Pharmaceutical Formulation by Thin-Layer ChromatographicDensitometric Method”, ISRN Analytical Chemistry. 2012.
  35. Jain N, Sharma BK, Jain R, Jain DK and Jain S, “RP-HPLC Method Development and Validation for Quantitative Estimation of Metoprolol Succinate and Telmisartan in Bulk Drug and Their Dosage Forms”, J Pharm Biomed Sci. 2012, 24 (24), 102-106.
  36. Raval M, ChikhaliaJ, Gosai M and Thumar K, “Method Development and Validation for Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Tablet Dosage Form by RP-HPLC”, Inventi Rapid: Pharm Ana & Qual Assur. 2012, 3, 1-6.
  37. Deshpande PB, Bhavnani VS, Gandhi SV, Pawar P and Gaikwad AK, “High Performance Thin Layer Chromatographic Determination of Metoprolol Succinate and Olmesartan in Combined Capsule Dosage Form”, Research J. Pharm. and Tech. 2012, 5(11), 1461-1464.
  38. Nawale PS, Shirkhedkar AA, Surana SJ and Patil AS, “Normal and ReversedPhase HPTLC Methods for Simultaneous Estimation of Telmisartan and Metoprolol Succinate in Pharmaceutical Formulation”, ISRN Analytical Chemistry. 2011, 1-6.
  39. Patel MM and Patel DD, “Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Pharmaceutical Dosage Form by RP-HPLC”, J Chromat Separation Techniq. 2012, 3, 8.
  40. Phale MD and Hamrapurkar PD, “A Validated and Simplified RP-HPLC of Metoprolol Succinate from Bulk Drugs”, Asian J. Research Chem. 2009, 2(2), 119 – 122.
  41. Singh B, Patel DK and Ghosh SK, “Development of Reverse-Phase HPLC Method for Simultaneous Analysis of Metoprolol Succinate and Hydrochlorothiazide in a Tablet Formulation”, Trop J Pharm Res. 2009, 8 (6), 539.
  42. Gaikwad AV, Khulbe P. HPLC Method Development for the Estimation of Empagliflozin in Bulk and Pharmaceutical Formulation. J. Pharm. Res. Int. [Internet]. 2022; 34(23B):22-31.  https://journaljpri.com/index.php/JPRI/article/view/6069
  43. Sushil D. Patil, Sayali K. Chaure, Maswood Ahmed Hafizur Rahman, Prajkta U. Varpe, Sanjay Kshirsagar.. Development and Validation of Simple UV- Spectrophotometric Method for the Determination of Empagliflozin. Asian J. Pharm. Ana. 2017; 7(1): 18-22. doi: 10.5958/2231-5675.2017.00004.7
  44. Manojkumar K. Munde, Nilesh S. Kulkarni, Rahul H. Khiste, Dhanya B. Sen. Development and Validation of Novel Analytical Method for Empagliflozin and Metformin Hydrochloride in Bulk and Pharmaceutical Dosage Form by Four Different Simultaneous Estimation Approaches using UV Spectroscopy. Research J. Pharm. and Tech 2020; 13(3):1236-1242. doi: 10.5958/0974-360X.2020.00228.0
  45. Vaishali M. Badgujar, Pritam S. Jain, Stability-Indicating RP-HPLC Method Development for the Determination of Empagliflozin, Asian Journal of Pharmaceutics. 2024, 18 (4): 1223
  46. Madure V, Barge V. Analytical Method Development and Validation of RP-HPLC Method For Estimation of Empagliflozin in Bulk and Pharmaceutical Dosage Form. J Neonatal Surg. 2025 Jul. 18[16];14(32S):5704-15. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/8360
  47. Joanna Wittckind Manoel, Determination of empagliflozin in the presence of its organic impurities and identification of two degradation products using UHPLC-QTOF/MS, Microchemical Journal. 161, 2021: 105795
  48. Siddiqui et al. Analytical Method Development and Validation for Simultaneous Estimation of Empagliflozin and Linagliptin in Bulk Drug and in Pharmaceutical Dosage Formulation by HPLC, Int. J. Pharm. Sci. Rev. Res., 81(1), 2023; 25, Pages: 147-151
  49. Jambhulkar1 Y et al. EMPAGLIFLOZIN: RP-HPLC based analytical method development and validation, ejpmr, 2024, 11(12), 291-297.
  50. Rahul S, Kumar BP and Avinash HR: Empagliflozin: a review on analytical and bio-analytical methods. Int J Pharm Sci & Res 2020; 11(9): 4144-51. doi: 10.13040/IJPSR.0975-8232.11(9).4144-51.
  51. Pathak, S., Mishra, P. Stability-indicating HPLC-DAD method for the determination of empagliflozin. Futur J Pharm Sci 7, 181 (2021). https://doi.org/10.1186/s43094-021-00329-w
  52. N. Padmaja and G. Veerabhadram, Development and validation of analytical method for Simultaneous estimation of Empagliflozin and Linagliptin in bulk drugs and combined dosage forms using UV-visible spectroscopy, Der Pharmacia Lettre, 2015, 7 (12):306-312.
  53. A. RAJA REDDY , J.LAVANYA , T. RAMA RAO , B. REVATHI, Analytical Method Development And Validation For Simultaneous Estimation Of Metformin And Empagliflozin in Bulk and Pharmaceutical Dosage Form By RP-HPLC, YMER. 21(11): 158-1869.
  54. Abhijeet N. Raut et al. Method development, validation by simultaneous estimation of Empagliflozin and Linagliptin by RP-HPLC Method. J Pharm Sci Innov. 2020;9(1):1-4. http://dx.doi.org/10.7897/2277-4572.091160
  55. Chandni Chandarana, Aarti Panchal, Vishal Modi. RP-HPLC Method Validation for Estimation of related Substances of Empagliflozin. Research Journal of Pharmacy and Technology. 2024; 17(10):5041-5. doi: 10.52711/0974-360X.2024.00775
  56. Dr. K M Khairul Alam1,* Tanbin Jahan Ferdousy, Development and Validation of an RP-HPLC Method for Determination of Empagliflozin in Empagliflozin Tablet, IJISRT. 8(5), 2023
  57. Mounika P Siridevi, Hemant T Kumar, Srinivasa Y Rao, Vara Prasad K Rao. RP-HPLC Method for Quantification of Empagliflozin in Pharmaceutical Formulation. Asian J. Pharm. Tech. 2019; 9(3):208-211. doi: 10.5958/2231-5713.2019.00035.7
  58. Heena Ninama, Shaileshkumar K. Koradia, Greenness assessment and stability-indicating HPTLC method for the concurrent analysis of empagliflozin and metoprolol succinate in a novel combined oral formulation, Drug Development and Industrial Pharmacy, 10.1080/03639045.2025.2594131, (1-14), (2025).
  59. Ninama H, Koradia SK. Greenness assessment and stability-indicating HPTLC method for the concurrent analysis of empagliflozin and metoprolol succinate in a novel combined oral formulation. Drug Dev Ind Pharm. 2025 Dec 4:1-14. doi: 10.1080/03639045.2025.2594131.
  60. Vandit Patel , Riddhi Trivedi , Munshi Mahammed Tanzil , Deepa R. Patel. Stability Indicating Method Development and Validation of Metoprolol Succinate and Empagliflozin by RP-HPLC in Synthetic Mixture, IJRASET. Volume 13 Issue XI, 2025.

Photo
Dr. Hitanshi Darji
Corresponding author

S.S.P. Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune 411062

Photo
Priyanka Patil
Co-author

S.S.P. Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune 411062

Photo
Arti Ingole
Co-author

S.S.P. Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune 411062

Photo
Dr. P. N. Sable
Co-author

S.S.P. Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune 411062

Priyanka Patil, Dr. Hitanshi Darji, Arti Ingole, Dr. P. N. Sable, Analytical Methods for the Metoprolol Succinate and Empagliflozin in Pharmaceutical Dosage Form: A Review, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 2, 167-181. https://doi.org/10.5281/zenodo.18454693

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