A Comprehensive Review of Analytical Techniques for the Quantification of Metoprolol Succinate

 

Chaudhari Hemangi Somnath*, Javesh K. Patil, Patil Bhagyashri Sandip,

Patil Bhagyashri Sunil

P.S.G.V.P Mandal’s College of Pharmacy Shahada, Dist – Nandurbar-425409 Maharashtra India.

*Corresponding Author E-mail: hemangichaudhari1133@gmail.com

 

ABSTRACT:

Metoprolol succinate (MTS) is a β1-selective adrenergic receptor blocker widely used for the treatment of hypertension, arrhythmias, heart failure, and myocardial infarction. Due to its significant therapeutic role, the accurate quantification and analysis of metoprolol succinate are essential. Various analytical methods have been developed for its estimation in bulk and pharmaceutical dosage forms, including spectroscopic and chromatographic techniques. This review explores different analytical methodologies for metoprolol succinate quantification, emphasizing spectrophotometric techniques and chromatography techniques. High-Performance Liquid Chromatography (HPLC) plays a crucial role in ensuring precise and reliable drug estimation. This review focuses on the significance of HPLC as the primary analytical technique for metoprolol succinate analysis. Among these, Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) is widely preferred due to its high sensitivity, accuracy, and precision. Several validated RP-HPLC methods have been reviewed, detailing their mobile phase composition, column specifications, flow rate, detection wavelength, and validation parameters such as linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ).

 

KEYWORDS: Analytical techniques, Metoprolol Succinate, UV, HPLC, RP-HPLC, Stability indicating RP-HPLC.

 

 


INTRODUCTION:

Metoprolol Succinate is considered as an ideal medication for developing suitable dosage forms. Metoprolol Succinate is a beta blocker used to treat hypertension and arrhythmias. Metoprolol Succinate has a biological half-life of 3-7hours.1 Metoprolol succinate is a beta1-selective (cardio selective) adrenoceptor blocking agent, for oral administration, available as extended-release tablets.2 Metoprolol (MTS) is chemically (RS)-1-(Isopropylamino)-3-[4-(2-methoxy ethylephenoxy] propaneLopresor, or -2-ol, is a drug that selectively blocks the β1 receptor. It is used to treat excessive blood pressure, chest pain caused by insufficient blood supply to the heart, and disorders with an unusually fast heart rate. It can also help avoid heart issues after a myocardial infarction and migraine headaches.3 The drug is highly sensitive, with even low dosages effectively blocking B1 adrenoreceptors.4,5 Therefore, drug quantification is crucial. Various methods, including spectrophotometry, LC, HPLC, RP-HPLC, and LC-MS, have been used to estimate metoprolol succinate in both pure and tablet dose forms.6

 

Metoprolol is a cardioselective β1-adrenergic blocker used to treat acute myocardial infarction (MI), heart failure, angina pectoris, and mild to moderate hypertension. It can treat supraventricular and tachyarrhythmias, as well as prevent migraine migraines. Metoprolol is structurally identical to bisoprolol, acebutanol and atenolol, with two substituents in the para position of the benzene ring. The presence of bulky substituents at the para position is suggested to contribute to the drugs’ β1- selectivity.3

 

Mechanism of Action:

Metoprolol binds to beta (1)-adrenergic receptors in the heart, competing with other neurotransmitters such catecholamines. Blocking Beta (1)-receptors lowers heart rate, cardiac output, and blood pressure.

 

Physical and Chemical property:

Metoprolol Succinate is a white powder. The IUPAC name for Metoprolol Succinate is Butanedioic acid;1-[4-(2-methoxyethyl) phenoxy]. - 3-(propan-2-ylamino) propan-2-ol. The chemical formula for metoprolol succinate is C34H56N2O10. The molecular weight is 652.8g/mol. It’s soluble in water, methanol, and slightly in ethanol7,8. The chemical structure of metoprolol succinate is shown in Figure 1.

 

 

Fig. 1: Chemical structure of metoprolol succinate.

 

Analytical techniques for method development:

In analytical chemistry the quantitative and qualitative determination of drugs the various techniques were used with their accuracy for method development.9

 

Spectroscopic techniques:

Spectroscopy was the primary technique used in method development. Our pharmacopoeias use a technique based on UV radiation absorption and chemical reactions.10 Spectroscopy relies solely on quantitative measurements, property transmission, and wavelength function. This strategy significantly reduces time and labor costs. This approach provides excellent precision and accuracy. This method is commonly used in pharmaceutical analysis to examine dose formulations and has grown in popularity over time.11

 

UV-Visible Spectroscopy:

UV-visible spectroscopy relies on energy, radiation, or electron excitation. The UV-Visible technique uses energy light to excite electrons. The sample wavelength is determined by the absorbance range of 200 to 800nm. Absorption occurred only when conjugated pi-electrons were present.12

 

FTIR Spectroscopy:

Infrared spectroscopy shifts absorption to a lower energy state, resulting in vibration and excitation of atoms and molecules. This approach identifies the functional group and original peaks of a molecule, allowing scientists to design new methods.13

 

Mass Spectroscopy (MS):

Mass spectroscopy involves ionizing molecules with high-energy electrons. The mass of each charge was carefully detected and evaluated using magnetic field fluctuations and electrostatic wave acceleration, ensuring correct weight of molecules.14

 

Nuclear Magnetic Resonance Spectroscopy (NMR)

Scientists have developed many approaches to analyze novel medication compounds. Nuclear magnetic resonance spectroscopy was commonly employed in medication development.15 This technique proved effective in identifying and analyzing medications using quantitative analysis to determine their molecules. This approach is useful for identifying drug composition, chemical products, pharmaceutical formulations, and biological fluids.16

 

Chromatographic Technique:

High Performance Thin Layer Chromatography (HPTLC):

This approach is widely used to identify, estimate, and assess the analytical profile of pharmacological compounds. This advanced technology will play a significant role in drug analysis.17 Its quick separation action and flexibility make it suitable for analyzing various medication components in the pharmaceutical industry. This technique has the advantage of allowing for quick drug analysis, easy handling, and cleaning of crude drug samples. This technique allows us to characterize chromatograms without time constraints for several parameters.18

 

High Performance Liquid Chromatography (HPLC):

High-performance liquid chromatography is a key technology for separating complicated mixtures of chemicals and molecules. This approach effectively targets chemical substances and biological components.19 In 1980, this approach was invented. With the adoption of HPLC, it became the first method to analyze bulk drug compounds as per USP-1980 standards. To ensure accuracy, precision, and a diverse range of samples, the HPLC method was used prior to drug analysis. A UV detector was utilized to estimate samples by HPLC and determine their wavelength. The UV detector procedure begins after numerous wavelength scanning programs have been applied.20

 

Thin Layer Chromatography (TLC):

Thin layer chromatography is a traditional method for analyzing chemicals in pharmaceuticals. This approach uses two phases: the mobile phase and the stationary phase.21 To prepare samples, the solid phase, adsorbent, and a thin layer of silica gel were distributed on a glass plate with an aluminum support. This approach was frequently used to analyze both inorganic and organic substances.TLC was chosen for compound analysis due to its minimal cleaning requirements, flexible mobile phase selection, high sample loading capacity, and cost-effectiveness. This approach proved particularly useful for analyzing bulk medication components.22

 

Gas Chromatography:

This technique effectively separates volatile and organic components. Gas chromatography separates compounds for quantitative measurement of numerous medication combinations, including compound tracing and parts per trillion. Gas chromatography is essential for analyzing pharmaceutical drugs and identifying contaminants.23

 

Reported Method for Metoprolol Succinate:

Metoprolol Succinate, a widely prescribed beta-1 selective adrenergic blocker, plays a vital role in managing hypertension, angina, and heart failure. Ensuring its efficacy, safety, and quality in pharmaceutical applications necessitates the development of precise and reliable analytical methods. Various advanced techniques have been reported for its quantification in biological matrices and pharmaceutical formulations, each serving a specific purpose. UV-spectrophotometry offers simplicity and cost-effectiveness for routine analysis, while high-performance liquid chromatography (HPLC) ensures high accuracy and sensitivity. Mass spectrometry, with its superior selectivity, is particularly valuable for pharmacokinetic and bioavailability studies. These methodologies collectively enhance the quality control and therapeutic monitoring of Metoprolol Succinate.

 

Tital 1: A Validated and Simplified RP-HPLC of Metoprolol Succinate from Bulk Drugs.

Methodology Overview – RP-HPLC was performed using a Spherisorb C-18 column (250×4.6mm, 10µm) with a mobile phase of acetonitrile: methanol: 10mM phosphate buffer (20:20:60, v/v), at a flow rate of 1.0ml/min. Detection was at 254nm, and Metoprolol succinate showed a retention time of 5.1min.

 

Validation parameters:

The RP-HPLC method showed good linearity (0.85–30µg/mL, r = 0.998), accuracy (98.05–100.59%), and precision (intra-day RSD < 0.62%, inter-day RSD < 1.26%). Sensitivity was confirmed with an LOQ of 0.75µg/mL and an LOD of 0.25µg/mL. MS was stable with no significant changes in retention time or peak area.24

 

Tital 2: Quantification of Metoprolol Succinate in balk and tablet Formulation by HPLC: Method development and validation.

Methodology overview – The HPLC method used an Inertsil ODS-2 column (150mm × 4.6mm, 5μm) with an isocratic mobile phase of ammonium acetate buffer: acetonitrile: acetic acid (84:15:1, v/v/v), pH adjusted to 3.8 with orthophosphoric acid. The flow rate was 1.0mL/min, and detection was performed at 280nm using UV.

 

Validation parameters: The method demonstrated good selectivity with no interference from excipients or mobile phase components. Linearity was excellent (R² = 0.9997) across 10–50μg/ml. Sensitivity was high with an LOD of 0.0189μg/ml and LOQ of 0.0630μg/ml. Precision was confirmed with %RSD below 0.137% (system) and 0.089% (method). Accuracy tests at 80%, 100%, and 120% showed recoveries between 99.81% and 100.56% (±0.109–0.374%)25.

 

Tital 3: Analytical Method Development and Validation of Metoprolol Succinate by High Performance Liquid Chromatography and Ultraviolet Spectroscopy Technique.

 

Methodology overview: HPLC and UV spectroscopy using a Water Spherisorb® column (5µm, 4.6 × 250mm). Mobile phase: acetonitrile, orthophosphoric acid, and water (pH 3.0). Flow rate: 2.0mL/min. Detection at 224nm using a PDA detector (Water Breeze 2) and Shimadzu UV-1800.

 

Validation parameters: Retention time was determined using a 30µg/mL solution with six HPLC injections at a 2mL/min flow rate over a 10minute run, yielding an average RT of 3.249±0.23min with acceptable %RSD. Linearity was observed over 10–50µg/mL for HPLC (R² = 0.9992) and 2–10µg/mL for UV-VIS (R² = 0.9998). Accuracy, assessed at 20, 30, and 40µg/mL in triplicate, showed a mean peak area of 8,216,289±1.02 with low %RSD. Sensitivity, as per ICH Q2 (R1) and USP guidelines, gave LOD and LOQ values of 0.0955µg/mL and 0.2896µg/mL, respectively26.

 

Tital 4: Analytical method development and validation for simultaneous estimation of Cilnidipine and metoprolol succinate by RP-HPLC.

Methodology overview: RP HPLC was performed using an Enable C18G column (250 × 4.6mm, 5µm) with a mobile phase of methanol: water (80:20, v/v) adjusted to pH 3.5 with orthophosphoric acid, at a flow rate of 1 mL/min and detection at 231.0nm.

 

Validation parameters: Cilnidipine and Metoprolol Succinate showed retention times of 4.092±0.12 min and 2.913±0.18min, respectively. Linearity was observed in the ranges of 2–10µg/mL for Cilnidipine and 10–50 µg/mL for Metoprolol Succinate. Intraday and interday precision (%RSD) were 0.597–0.977 and 1.829–1.959 for Cilnidipine, and 0.506–0.737 and 1.758–1.993 for Metoprolol Succinate. Mean recovery ranged from 98.11–100.76% for Cilnidipine and 99.65–100.24% for Metoprolol Succinate. LOD/LOQ were 0.05332/0.161577µg/mL for Cilnidipine and 0.226354/0.685921 µg/mL for Metoprolol Succinate27.

 

Tital 5: Method Development and Validation for Simultaneous Estimation of Benidipine Hydrochloride and Metoprolol Succinate in Tablet dosage from.

Methodology overview: HPLC was performed using a Shimadzu LC-20AT with a C18 (250 × 4.6mm, 5µm) Hypersil BDS column. The mobile phase consisted of potassium dihydrogen phosphate buffer (pH 4.0) and methanol (65:35 v/v), with detection at 269nm. The concentration ranges were 4–12µg/mL for benidipine and 25–75µg/mL for metoprolol. Retention times were 3.4 min (metoprolol) and 5.9min (benidipine).

 

Validation parameters: The method showed high recovery for benidipine (99.59%) and metoprolol (99.39%). Linearity was excellent with R² values of 0.9997 (benidipine, 4–12µg/mL) and 0.9995 (metoprolol, 25–75µg/mL). LOD/LOQ were 0.204/0.618 µg/mL for benidipine and 1.738/5.266µg/mL for metoprolol28.

 

Tital 6: stability indicating HPLC method for Simultaneous estimation of metoprolol succinate and telmisartan.

Methodology overview: Stability-indicating HPLC was performed using a HiQ Sil C18 column (250 × 4.6mm, 5 µm) with a mobile phase of methanol, 10mM potassium dihydrogen phosphate buffer, and 10mM hexane sulphonic acid (80:10:10, v/v/v). The flow rate was 1 mL/min, and detection was at 223nm.

 

Validation parameters: Metoprolol succinate and Telmisartan showed retention times of 3.07 and 5.65 min, with linearity ranges of 5–80µg/mL and 5–60 µg/mL, respectively (R²>0.998). Both drugs demonstrated high precision intraday and interday (% mean ~99.7–99.8). LOD and LOQ were low (MET: 0.013 and 0.041µg/mL; TEL: 0.010 and 0.031µg/mL). Forced degradation under acidic conditions produced distinct degradation peaks at 3.57 and 4.21 min for MET, and 6.30min for TEL29.

 

Tital 7: Rp-Hplc Method development and validation for the simultaneous estimation of chlorthalidone and metoprolol succinate in bulk and formulation.

Methodology overview: Reverse phase HPLC was performed using a Thermo Scientific BDS column (250 × 4.6mm, 5µm). The mobile phase was acetonitrile and 0.1% trimethylamine (90:10 v/v), pH adjusted to 4.5 with 0.1% orthophosphoric acid. Flow rate was 1 ml/min, with UV detection at 224nm.

 

Validation parameters: Retention times were 2.6 min for Chlorthalidone and 6.5min for Metoprolol Succinate. Linearity ranges were 4–14µg/ml and 16–56µg/ml, respectively. Intraday precision (%RSD) was 0.45 for Chlorthalidone and 0.32 for Metoprolol Succinate; interday precision was 0.33 and 0.26. LODs were 0.61 µg/ml (Chlorthalidone) and 2.63µg/ml (Metoprolol Succinate), with LOQs of 1.86µg/ml and 7.98µg/ml30.

 

Tital 8: Development and validation of a stability Indicating RP-HPLC method for simultaneous Estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage Form.

Methodology overview: Reverse phase HPLC was performed using a YMC-Pack CN column (250 × 4.6 mm, 5μm) with a mobile phase of 0.05% TFA and acetonitrile (70:30v/v). The flow rate was 1.0ml/min, and detection was at 220nm. Retention times were 7.9 min for Olmesartan Medoxomil and 4.1min for Metoprolol Succinate.

 

Validation Parameters: The linearity range for both drugs was 5–35μg/ml with a recovery of 100±2%. Precision showed intraday RSD of 0.45% (Olmesartan) and 0.85% (Metoprolol), and interday RSD of 0.61% and 0.94%, respectively. Specificity was confirmed by separating degradation products. LOD and LOQ were 0.085 and 0.259μg/ml for Olmesartan, and 1.05 and 3.19 μg/ml for Metoprolol31.

 

Tital 9: Development and Validation of an RP-HPLC Method for Simultaneous Determination of Trimetazidine Hydrochloride and Metoprolol Succinate.

Methodology overview:

Reverse phase HPLC was performed using an Enable C18 column (250 x 4.6mm, 5μm) with a mobile phase of water: methanol: acetonitrile (45:45:10, v/v/v) at pH 3.0 (adjusted with ortho-phosphoric acid). The flow rate was 1mL/min, detection at 274nm. Retention times: TMZ 2.61±0.175 min, METO 4.12±0.129 min.

 

Validation parameters: Linearity was established for TMZ (20–120μg/mL, r²=0.9977) and METO (27–162 μg/mL, r²=0.9970). LODs were 1.205μg/mL (TMZ) and 1.53μg/mL (METO), with LOQs of 3.652μg/mL and 4.64μg/mL, respectively. Precision showed %RSD <2; intraday precision ranged from 1.226–1.425 (TMZ) and 1.142–1.242 (METO), while interday precision ranged from 1.860–1.903 (TMZ) and 1.861–1.956 (METO)32.

 

Tital 10: Development and validation of RPHPLC method for simultaneous determination of metoprolol and amlodipine in tablet dosage Form

Methodology overview – Reverse phase HPLC was performed using a Welchrom RP-C18 column (250 × 4.6 mm, 5µm) on a Shimadzu LC-20AT system. The mobile phase was 10mM phosphate buffer (pH 3.0) and acetonitrile (50:50, v/v) at 1.0mL/min flow rate. Detection was at 235 nm using a Shimadzu SPD-20A UV-Vi’s detector.

 

Validation parameters: Metoprolol and Amlodipine showed retention times of 2.687 and 3.797 min, respectively. Both drugs exhibited excellent linearity (r² = 0.9999) within 5-25 µg/mL for Metoprolol and 1-5 µg/mL for Amlodipine. LODs were 0.125 µg/mL (Metoprolol) and 0.102 µg/mL (Amlodipine), while LOQs were 0.381 µg/mL and 0.311 µg/mL, respectively. Precision was high with intra-day %RSD of 0.25 (Metoprolol) and 0.83 (Amlodipine), and inter-day %RSD of 0.20 and 0.8733.


 

 

Table 1: Analytical Techniques and Method Conditions for Estimation of Metoprolol Succinate as a Single Drug.

Sr. No.

Article Tital

Technique used

Mobile phase

Flow rate mL/min

Detection

1

A Validated and Simplified RP-HPLC of Metoprolol Succinate from Bulk Drugs Methodology Overview.

Reverse phase liquid chromatographic method (RP-HPLC)

Acetonitrile: Methanol: 10 mM aqueous phosphate buffer (20:20:60% v/v).

1.0 ml/min.

254 nm.

2

Quantification of Metoprolol Succinate in balk and tablet Formulation by HPLC: Method development and validation.

High Performance liquid chromatography

Ammonium acetate buffer: acetonitrile: acetic acid [84:15:1 v/v/v].

 1.0 ml/min

280 nm

3

Analytical Method Development and Validation of Metoprolol Succinate by High Performance Liquid Chromatography and Ultraviolet Spectroscopy Technique.

HPLC and ultraviolet spectroscopy technique

CAN, orthophosphoric acid, water (pH 3.0).

2.0 ml/min.

224 nm



Table 2- Validation Parameters of HPLC Methods for Single-Component Analysis of Metoprolol Succinate.

Sr. No.

Article Title

Validation Parameters

Selectivity

Linearity µg/mL

Precision

Accuracy

LOD and LOQ

Stability

1.

A Validated and Simplified RP-HPLC of Metoprolol Succinate from Bulk Drugs Methodology Overview

NS

0.85–30 µg/mL

 Intra-day precision: RSD < 0.62% Inter-day precision: RSD < 1.26%

 98.05% to 100.59%.

LOD – 0.25 µg/ml LOQ – 0.75 µg/ml

No significant changes in retention time and peak area of MS.

2.

Quantification of Metoprolol Succinate in balk and tablet Formulation by HPLC: Method development and validation

No interference

10-50 μg/ml

Intra day precision %RSD- 0.137, Interday precision %RSD-0.089

 99.81% to 100.56%

LOD: 0.0189 μg/ml LOQ: 0.0630 μg/ml

The solutions are stable if the assay difference from 0 to 24 hr and 30 hr is ≤2%.

3.

Analytical Method Development and Validation of Metoprolol Succinate by High Performance Liquid Chromatography and Ultraviolet Spectroscopy Technique

NS

HPLC: 10–50 µg/ml (R² = 0.9992). UV-VIS: 2–10 µg/ml (R² = 0.9998).

Intraday precision %RSD- 0.78, Interday precision %RSD- 0.86

8,216,289 ± 1.02

LOD- 0.0955 µg/ml LOQ- 0.2896 µg/ml

NS

 


 

Table 3- Analytical Techniques and Chromatographic Conditions for Simultaneous Estimation of Metoprolol Succinate in Combination with Other Drugs.

Sr. No.

Article Tital

Technique used

Mobile phase

Flow rate

Detection

1

Analytical method development and validation for simultaneous estimation of Cilnidipine and metoprolol succinate by RP-HPLC

Reverse phase high performance liquid chromatography (RPHPLC)

Methanol: Water (80:20, v/v) with pH adjusted to 3.5 using orthophosphoric acid.

1 ml/ min

 231.0 nm.

2

Method Development and Validation for Simultaneous Estimation of Benidipine Hydrochloride and Metoprolol Succinate in Tablet dosage from

High Performance liquid chromatography

Potassium Dihydrogen Phosphate Buffer (pH 4.0): Methanol (65:35% v/v).

 

269 nm

3

Stability indicating HPLC method for Simultaneous estimation of metoprolol succinate and telmisartan.

Stability indicating HPLC

Methanol: 10 mM potassium dihydrogen phosphate buffer: 10 mM hexane sulphonic acid (80:10:10, v/v/v).

1 ml / min

223.0 nm

4

RP-HPLC Method development and validation for the simultaneous estimation of chlorthalidone and metoprolol succinate in bulk and formulation

Reverse phase high performance liquid chromatography

Acetonitrile: 0.1% Trimethylamine (90:10 % v/v).

 1 ml / min

224 nm

5

Development and validation of a stability Indicating RP-HPLC method for simultaneous Estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage Form

Reverse phase high performance liquid chromatography

0.05% Trifluoroacetic acid (TFA) and Acetonitrile (CAN) in a 70:30 v/v ratio.

1.0 ml / min

220 nm.

6

Development and Validation of an RP-HPLC Method for Simultaneous Determination of Trimetazidine Hydrochloride and Metoprolol Succinate

Reverse phase high performance liquid chromatography

Methanol: Acetonitrile (45:45:10, v/v/v), pH adjusted to 3.0 using ortho-phosphoric acid.

1 ml / min

274.0 nm.

7

Development and validation of RPHPLC method for simultaneous determination Of metoprolol and amlodipine in tablet dosage Form

Reverse phase high performance liquid chromatography

10 mM Phosphate buffer (pH 3.0): Acetonitrile (50:50, v/v).

1.0 ml / min

235 nm


Table 4- Validation Parameters of RP-HPLC Methods for Combination Drug Analysis Involving Metoprolol Succinate.

Sr.no.

Article Title

Validation Parameters

Linearity µg/mL

Precision

Accuracy

LOD and LOQ

1.

Analytical method development and validation for simultaneous estimation of Cilnidipine and metoprolol succinate by RP-HPLC

 Cilnidipine: 2 – 10 µg/ml. Metoprolol Succinate: 10 – 50 µg/ml

 Cilnidipine-Intraday Precision: 0.597 – 0.977, Interday Precision: 1.829 – 1.959 Metoprolol Succinate- Intraday Precision: 0.506 – 0.737, Interday Precision: 1.758 – 1.993

Clinidipine 98.11 – 100.76 %, metoprolol succinate 99.65 -100.24 %

Clinidipine - LOD 0.05332 µg/ml, LOQ 0.161577 µg/ml Metoprolol succinate – LOD 0.226354 µg/ml, LOQ 0.685921 µg/ml

2.

Method Development and Validation for Simultaneous Estimation of Benidipine Hydrochloride and Metoprolol Succinate in Tablet dosage from

Metoprolol Succinate of 25-75 µg/ml and Benidipine Hydrochloride of 4-12µg/ml

Metoprolol succinate – Intraday precision – 0.633-0.674, Interday precision – 0.369-0.695, Benidipine hydrochloride – Intraday precision – 0.912-0.836 Interday precision – 0.594-1.160

Metoprolol succinate 99.43- 99.43 %, Benidipine hydrochloride 99.105- 100.89%

Metoprolol Succinate- LOD: 1.738 µg/ml, LOQ: 5.266 µg/ml Benidipine Hydrochloride- LOD: 0.204 µg/ml, LOQ: 0.618 µg/ml

3.

Stability indicating HPLC method for Simultaneous estimation of metoprolol succinate and telmisartan.

Metoprolol succinate: 5-80 µg/mL., Telmisartan: 5-60 µg/mL.

Metoprolol succinate – intraday precision – 99.82, Interday precision – 99.76, Telmisartan – intraday precision – 99.75, Interday precision-99.70.

Metoprolol succinate – 99.84 %, Telmisartan -99.80%.

Limit of Detection (LOD): Metoprolol Succinate (MET): 0.013 µg/mL, Telmisartan (TEL): 0.010 µg/Ml Limit of Quantification (LOQ): Metoprolol Succinate (MET): 0.041 µg/mL, Telmisartan (TEL): 0.031 µg/mL

4.

Rp-Hplc Method development and validation for the simultaneous estimation of chlorthalidone and metoprolol succinate in bulk and formulation

Chlorthalidone: 4-14 µg/ml, Metoprolol Succinate: 16-56 µg/ml.

intraday precision – Chlorthalidone - %RSD 0.45, metoprolol succinate - %RSD 0.32. Interday precision – Chlorthalidone -%RSD 0.33, metoprolol succinate - %RSD 0.26.

Chlorthalidone – 101.0%, Metoprolol succinate – 101.2%.

LOD Values: Chlorthalidone: 0.61 µg/ml, Metoprolol Succinate: 2.63 µg/ml LOQ Values: Chlorthalidone: 1.86 µg/ml, Metoprolol Succinate: 7.98 µg/ml

5.

Development and validation of a stability Indicating RP-HPLC method for simultaneous Estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage Form

5‑35 μg/ml for both drugs.

intraday precision – OLME – 0.45%, METO – 0.85% Interday precision – OLME- 0.61%, METO- 0.94%

100 ± 2%.

Olmesartan medoxomil - LOD: 0.085 μg/ml, LOQ: 0.259 μg/ml Metoprolol succinate-LOD: 1.05 μg/ml, LOQ: 3.19 μg/ml

6.

Development and Validation of an RP-HPLC Method for Simultaneous Determination of Trimetazidine Hydrochloride and Metoprolol Succinate

TMZ: 20-120 μg/mL (r² = 0.9977). METO: 27-162 μg/mL (r² = 0.9970).

Intraday Precision (%RSD): Trimetazidine Hydrochloride: 1.226 – 1.425, Metoprolol Succinate: 1.142 – 1.242 Interday Precision (%RSD): Trimetazidine Hydrochloride: 1.903 – 1.860, Metoprolol Succinate: 1.861 – 1.956

Trimetazidine Hydrochloride - 99.53%, Metoprolol succinate – 101.31%.

Limit of Detection (LOD): TMZ: 1.205 μg/mL, METO: 1.53 μg/mL Limit of Quantitation (LOQ): TMZ: 3.652 μg/mL, METO: 4.64 μg/mL

7.

Development and validation of RPHPLC method for simultaneous determination of metoprolol and amlodipine in tablet dosage Form

Metoprolol: Linear over 5-25 µg/mL (r² = 0.9999). Amlodipine: Linear over 1-5 µg/mL (r² = 0.9999).

Intra-Day Precision (%RSD): Metoprolol: 0.25242, Amlodipine: 0.831 Inter-Day Precision (%RSD): Metoprolol: 0.20335, Amlodipine: 0.873

Metoprolol succinate –100.265 ± 0.425% Amlodipine -100.340 ± 1.645%

Limit of Detection (LOD): Metoprolol: 0.125 µg/mL Amlodipine: 0.102 µg/mL Limit of Quantitation (LOQ): Metoprolol: 0.381 µg/mL Amlodipine: 0.311 µg/mL

 


CONCLUSION:

This review compiles and evaluates previously published analytical techniques for the quantification of Metoprolol succinate in various pharmaceutical and biological matrices. HPLC, particularly RP-HPLC is the most widely employed method due to its accuracy, precision, and robustness. Numerous studies have developed and validated methods for determining Metoprolol succinate in bulk drug and formulations. Additionally, other techniques like spectrophotometry have been explored.

 

This study makes a significant contribution by systematically synthesizing previous research on Metoprolol succinate methodologies. It serves as a valuable resource for researchers and pharmaceutical analysts seeking reliable analytical approaches for quality control and pharmacokinetic investigations.

 

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2.      MetoprololSuccinate: http://dailymed.nlm.nih.gov/dailymed/drugInfo.Cfm?id=16753#nlm34089-3

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Received on 10.05.2025      Revised on 02.06.2025

Accepted on 18.06.2025      Published on 08.10.2025

Available online from October 15, 2025

Asian Journal of Pharmaceutical Analysis. 2025; 15(4):306-313.

DOI: 10.52711/2231-5675.2025.00048

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