1. INTRODUCTION:

Fimasartan, an angiotensin II receptor blocker (ARB), was developed by Boryung Pharmaceutical in South Korea and approved in 2010 for hypertension. It is the first ARB from Korea designed for high selectivity and efficacy. Research began in the early 2000s, with clinical trials confirming its safety and benefits. It is now used in monotherapy and combination therapies for managing hypertension and related cardiovascular conditions. Its chemical structure, (2-butyl-4-chloro-1-{[2′-(1H-tetrazol-5-yl)-1,1′-biphenyl-4-yl] methyl}imidazole-5-carboxylic acid), exhibits a high binding affinity ^[1]. Fimasartan’s unique properties, including its lipophilicity and potent antagonistic activity, make it an effective antihypertensive agent.² Fimasartan selectively inhibits AT1R, which is key in regulating blood pressure and fluid balance.³ By blocking this receptor, Fimasartan prevents angiotensin II from causing vasoconstriction and aldosterone secretion. This leads to vasodilation, reduced blood pressure, and improved cardiovascular outcomes.⁴ Emerging evidence also suggests benefits in renal conditions such as diabetic nephropathy.⁵ Robust analytical methods are essential for ensuring pharmaceutical compounds' efficacy, safety, and quality. Techniques such as HPLC, LC-MS/MS, and UV-visible spectroscopy play crucial roles in detecting impurities, studying pharmacokinetics, and ensuring compliance with regulatory standards.⁶ This review summarizes existing analytical methods for Fimasartan, highlighting their advantages, limitations, and applications in pharmaceutical research.

2. Mechanism of Action:

Fimasartan selectively blocks AT1R, reducing vascular resistance, aldosterone secretion, and fluid retention. This leads to vasodilation and lowered blood pressure.⁷ Unlike non-selective ARBs, Fimasartan minimizes adverse effects linked to angiotensin II type 2 receptor stimulation, such as hyperkalemia and renal dysfunction.⁸

2.1 Physical and Chemical Properties:

Fimasartan's IUPAC name is 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-imidazole-5-carboxylic acid. Fimasartan, a non-peptide angiotensin II receptor blocker (ARB), has a molecular weight of roughly 459.54 g/mol and the molecular formula C₂₆H₂₉N₅O₃. It is categorised as a class II drug under the Biopharmaceutics Classification System (BCS) and is a white to off-white crystalline powder with poor aqueous solubility. The compound exhibits high lipophilicity, with a log P value indicative of its strong affinity for lipid membranes. Fimasartan has a melting point in the range of 190–200°C and demonstrates stability under normal storage conditions, though it may undergo degradation in extreme pH environments. It is slightly soluble in organic solvents such as methanol and ethanol but shows limited solubility in water. The chemical structure of Fimasartan includes a benzimidazole moiety and a tetrazole ring, which contribute to its high binding affinity for the AT₁ receptor, leading to its potent antihypertensive activity.⁹

Fig. 1: Chemical Structure of Fimasartan

2.2 Pharmacokinetics of Fimasartan

After oral administration, Fimasartan is quickly absorbed, reaching peak plasma concentrations (Cmax) in 0.5 to 3 hours. Its absorption is influenced by factors such as food intake, which can slightly delay Tmax without affecting the overall bioavailability. Fimasartan exhibits dose-proportional pharmacokinetics within the therapeutic range.¹⁰ Once absorbed, Fimasartan binds extensively (over 99%) to plasma proteins, primarily albumin. This high protein-binding affinity aids in its sustained therapeutic effect by ensuring a stable concentration in the bloodstream. The apparent volume of distribution indicates limited penetration into tissues outside the systemic circulation.¹¹

2.3 Pharmacodynamics of Fimasartan:

The liver metabolizes Fimasartan predominantly via oxidative pathways and glucuronidation. Cytochrome P450 enzymes play a minimal role, reducing the likelihood of significant drug-drug interactions. Its metabolites are pharmacologically inactive, ensuring the drug's activity is confined to the parent compound.¹² Fimasartan is primarily excreted unchanged in feces (about 80%), with a smaller fraction eliminated via urine. Its elimination half-life ranges from 5 to 16 hours, depending on the dose and individual patient factors, allowing for once-daily dosing in most clinical scenarios. The clearance mechanisms ensure minimal accumulation with repeated dosing.¹³ Fimasartan is primarily indicated for essential hypertension. Studies highlight its role in reducing proteinuria, particularly in diabetic nephropathy, and its nephroprotective and cardioprotective effects.¹⁴ Emerging research supports its potential use in chronic kidney disease and cardiovascular complications.¹⁵

3. Analytical Techniques for Fimasartan:

This section introduces the analytical techniques used to evaluate Fimasartan, providing an overview of chromatographic, spectroscopic, and hyphenated methods and emphasizing their applications in pharmaceutical analysis.¹⁶

3.1 Chromatographic Methods:

Chromatographic techniques are vital for the analytical assessment of Fimasartan, allowing for its separation, identification, and quantification in various matrices.¹⁷ Below are the primary techniques used:

3.1.1 High-Performance Liquid Chromatography (HPLC):

A widely employed method for quantifying Fimasartan in bulk drug substances and pharmaceutical formulations due to its precision, reproducibility, and adaptability. HPLC utilizes a stationary phase and a liquid mobile phase to effectively separate components, enabling accurate determination of drug content and impurities.¹⁸

3.1.2 Ultra-Performance Liquid Chromatography (UPLC):

Operating at higher pressures compared to HPLC, UPLC enables faster analysis and higher resolution, making it particularly advantageous for stability studies where quick and precise detection of degradation products is necessary.¹⁹

3.1.3 Reverse-Phase Liquid Chromatography (RP-HPLC):

RP-HPLC, a widely used analytical method for estimating Fimasartan in pharmaceutical formulations and bulk, uses a polar mobile phase and a non-polar stationary phase to achieve effective separation. This method offers high sensitivity, selectivity, and robustness, making it suitable for routine quality control and stability studies.²⁰

3.1.4 High-Performance Thin Liquid Chromatography (HPTLC):

A sophisticated chromatographic method for both qualitative and quantitative compound analysis is High-Performance Thin Layer Chromatography (HPTLC). It offers high resolution, automation, and reproducibility compared to conventional TLC. HPTLC is widely used in pharmaceutical, food, and environmental analysis for identifying and quantifying complex mixtures efficiently.²¹

3.1.5 Liquid Chromatography-Tandem Mass Spectrometry (LCMS-MS):

A potent analytical method that combines mass spectrometry for detection and liquid chromatography for separation is called Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). It provides high sensitivity, specificity, and accuracy, making it ideal for pharmaceutical, forensic, environmental, and biological analyses, including drug quantification, metabolite profiling, and biomarker identification.²²

3.2 Spectroscopic Methods:

Spectroscopic methods study the interaction of matter with electromagnetic radiation, providing valuable insights into the chemical structure and molecular behavior of substances like Fimasartan.²³ Below are some standard spectroscopic methods:

3.2.1 UV-visible spectroscopy:

This method provides information about a substance's electronic transitions by measuring how much ultraviolet and visible light it absorbs. UV-Vis spectroscopy is widely used to quantitatively estimate compounds like Fimasartan in bulk and pharmaceutical dosage forms ^[24]. It is simple, cost-effective, and efficient for routine analysis, although it requires compounds to absorb in the UV or visible range.²⁵

4. Analytical Method Development:

Analytical method development ensures accurate, precise, and reproducible drug analysis. It involves selecting suitable techniques like HPLC, UV spectrophotometry, or LC-MS based on drug properties. Key steps include method selection, optimization, validation (specificity, accuracy, precision, robustness), and regulatory compliance. A well-developed method ensures drug quality, stability, and efficacy, which are essential for pharmaceutical formulation, regulatory approval, and routine quality control in research and industry.

5. Validation:

In analytical chemistry, method validation is a crucial procedure that guarantees a method's accuracy and dependability. Strict guidelines for validating analytical methods are provided by regulatory agencies like the U.S. Food and Drug Administration (FDA) and the International Council for Harmonisation (ICH). These guidelines emphasize elements such as system suitability, assessing whether the system is operating correctly before starting an analysis, and method robustness, which tests the method’s ability to perform consistently under slight variations in experimental conditions.²⁶

5.1 Parameters (Component) of Method Validation:

Several key parameters are considered when validating an analytical method to ensure its performance and reliability:

1. Accuracy: The degree to which test results resemble the actual value (expressed as a percentage of recovery).

2. Precision: The level of consistency between each test result.

3. Linearity: The capacity to get test results over a specified range that are exactly proportionate to the analyte concentration.

4. Detection Limit (LOD): The smallest quantity of analyte that is detectable but not always measurable.

5. Quantitation Limit (LOQ): The minimum quantity of analyte that can be measured with a satisfactory level of precision and accuracy.²⁷

6. Specificity: The capacity to evaluate the analyte free from interference from other elements such as matrix effects, degradation products, or impurities.²⁸

7. Range: The range of analyte concentrations that the method can measure with linearity, accuracy, and precision.²⁹

8. Robustness: The capacity to stay unaffected by minor changes in method parameters (such as pH, temperature, flow rate, and the composition of the mobile phase).³⁰

6. Reported Method for Fimasartan:

The development of reliable analytical methods is crucial for ensuring the quality, efficacy, and safety of Fimasartan in both bulk and pharmaceutical formulations. Over the years, various analytical techniques have been designed and validated to meet regulatory standards and support pharmacokinetic, stability, and impurity studies. Researchers have explored diverse methods, including High-Performance Liquid Chromatography (HPLC), Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), Ultra-Performance Liquid Chromatography (UPLC), and High-Performance Thin Layer Chromatography (HPTLC), each offering distinct advantages in terms of sensitivity, precision, and speed. Many studies have focused on developing stability-indicating methods to ensure accurate measurement of Fimasartan even in the presence of degradation products under various stress conditions. This section compiles and evaluates key reported methods, summarizing critical parameters such as retention time, mobile phase composition, detection wavelengths, and precision values. The overview aims to provide a comprehensive understanding of existing methodologies, highlighting their practical applications and guiding future advancements in Fimasartan analysis.

1. Hyeon Woo Moon and his co-workers published the paper in the year 2014. For stability-indicating RP-HPLC analytical method development and validation for the simultaneous estimation of Fimasartan and Amlodipine in combination tablets. For the simultaneous measurement of amlodipine and Fimasartan in tablet dosage form, a straightforward, quick, accurate, and precise and robust HPLC method was created. Additionally, the stability of the active ingredients was assessed under both stress and normal circumstances. The isocratic elution was accomplished by Nucleosil C18 column (250 mm 4.6 mm, 5 mm) at 40 C. The mobile phase consisted of acetonitrile and 0.02 M monopotassium phosphate buffer (pH 2.2) in the ratio of 50:50 (v/v) was eluted at 1.0 ml/min. For eight minutes, the eluent was observed by the UV detector for amlodipine and Fimasartan at 237 nm.³¹

Parameters	Description
Column Name	Nucleosil C18 column (250 mm × 4.6 mm, 5 µm)
Mobile Phase	Acetonitrile and 0.02 M monopotassium phosphate buffer (pH 2.2) (50:50 v/v)
Flow Rate	1.0 ml/min
Detection	237 nm
Retention Time	Fimasartan: 5.24 ± 0.03 min, Amlodipine: 2.64 ± 0.08 min
Precision	<1% RSD

2. Seo Hyun Yoon and co-workers published the paper in the year 2015. For LC-MS/MS analytical method development and validation for measuring the amount of Fimasartan in human plasma. (LC–MS/MS) method for the quantification of a newly The LC–MS/MS) 3 method was created and validated for the measurement of Fimasartan (BR-A657, Kanarbw), a recently developed antihypertensive drug, in human plasma. Using acetonitrile and simple protein precipitation, Fimasartan and the internal standard (IS, BR-A563) were extracted and separated on a Phenyl-Hexyl column (Lunaw, 5 mm, 50 mm 3 2.0 mm, Phenomenex) with gradient conditions of mobile phase B (100% acetonitrile with 0.1% formic acid) and mobile phase A (distilled water with 0.1% formic acid) at a flow rate of 0.25 mL/min. The mass spectrometer used multiple reaction monitoring mode to detect and quantify the IS at m/z 524.3-204.9 and m/z 500.2! 221.2 for Fimasartan. The assay had a lower limit of quantification of 0.5 ng/mL and was linear over a calibration range of 0.5 500 ng/mL.³²

Parameters	Description
Column Name	Phenyl-Hexyl column (Luna, 5 µm, 50 mm × 2.0 mm, Phenomenex)
Mobile Phase	A: Distilled water with 0.1% formic acid, B: Acetonitrile with 0.1% formic acid (gradient elution)
Flow Rate	0.25 mL/min
Detection	LC-MS/MS (MRM mode) at m/z 500.2 → 221.2 for Fimasartan
Retention Time	2.95–3.02 min
Precision	<14.9% RSD
Lower Limit of Quantification (LLOQ)	0.5 ng/mL
Calibration Range	0.5–500 ng/mL

3. Ji Yeon Hyun and co-workers published the paper in the year 2015. UPLC-MS/MS analytical method development and validation for the quantification of Fimasartan in human plasma. Fimasartan is a novel angiotensin II receptor blocker with strong anti-hypertensive activity. This study developed and thoroughly validated a faster and more sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method to detect Fimasartan in human plasma. Using a multiple reaction monitoring mode, MS/MS was used to quantify the analytes at m/z 502.2 → 207.1 for Fimasartan and m/z 526.3 → 207.1 for the internal standard (IS, BR-A-563). From 3 to 1000 ng/mL, the method demonstrated a linear response (r > 0.9950). The accuracy values were 93.3 to 100.1% for the interday and 86.9 to 98.2 for the intraday. The intra- and inter-day precision values were 2.0 – 3.1 and 0.8 – 8.0%, respectively.³³

Parameters	Description
Column Name	Phenomenex Kinetex C18 column (150 × 2.1 mm, 2.6 µm)
Mobile Phase	A: 5 mM ammonium acetate with 0.1% formic acid, B: Acetonitrile with 0.1% formic acid (gradient elution)
Flow Rate	0.4 mL/min
Detection	UPLC-MS/MS (MRM mode) at m/z 502.2 → 207.1 for Fimasartan
Retention Time	2.91 min
Precision	Intra-day: 2.0–3.1% RSD, Inter-day: 0.8–8.0% RSD
Lower Limit of Quantification (LLOQ)	3 ng/mL
Calibration Range	3–1000 ng/mL

4. Charu P. Pandya and co-workers published the paper in the year 2017. For the development and validation of a stability-indicating RP-HPLC analytical method for Fimasartan estimation in the presence of degradation products. To determine the amount of Fimasartan in a synthetic mixture, a stability-indicating high performance liquid chromatographic method was created and verified. Fimasartan is used to treat high blood pressure. Reverse phase chromatography was carried out on a Shimadzu LC 20AD pump (binary) and Shimadzu PDA-M20A Diode Array Detector using a Hypersil BDS C18 column (250 x 4.6 mm, 5μm) and a mobile phase that contained phosphate buffer pH3: acetone (50:50, v/v) at a flow rate of 1 millilitre per minute. The wavelength used for detection was 262 nm. Regression equation y=78487x+66095 showed linearity in the concentration range of 5-30μg/mL (R2=0.999). The results showed that the LOQ was 4.67μg/ml and the LOD was 1.54μg/ml. Stress conditions including acidic, alkaline, oxidative, photolytic, and thermal degradations were applied to Fimasartan.³⁴

Parameters	Description
Column Name	Hypersil BDS C18 column (250 × 4.6 mm, 5 µm)
Mobile Phase	Phosphate buffer (pH 3.0) and Acetonitrile (50:50 v/v)
Flow Rate	1.0 mL/min
Detection	262 nm
Retention Time	7.306 ± 0.052 min
Precision	Intra-day: 0.85% RSD, Inter-day: 1.12% RSD
Limit of Detection (LOD)	1.54 µg/mL
Limit of Quantification (LOQ)	4.67 µg/mL
Linearity Range	5–30 µg/mL (R² = 0.999)

5. Shraddha Badade and co-workers published the paper in the year 2019. For the development and validation of the HPTLC analytical method for the measurement of Fimasartan in pharmaceutical dosage forms and bulk. As the stationary phase, the technique used TLC 20 cm × 10 cm aluminium-backed TLC plates coated with 200μm layers of silica gel 60F254 S. The solvent system is toluene, methanol, ethyl acetate, and formic acid (8:1.2:0.9:0.3 v/v). Fimasartan was assigned a compact spot by the system (0.6 ±0.02). The wavelength at which the Spectro densitometric scanning-integration was carried out was 265 nm. In the concentration range of 800-2800 ng for Fimasartan, the regression equation data for the calibration plot demonstrated a good linear relationship with r2 = 0.9997. Through their forced degradation studies, the method's precision, accuracy, robustness, and ruggedness were validated. 52.81 and 160.03, respectively, were determined to be the limits of quantification and detection. This analysis demonstrates the reproducibility and selectivity of the provided method for determining Fimasartan.³⁵

Parameters	Description
Stationary Phase	Silica gel 60F254 S (200 μm layer)
Mobile Phase	Toluene: Methanol: Ethyl acetate: Formic acid (8:1.2:0.9:0.3 v/v)
Rf Value	0.6 ± 0.02
Detection	265 nm
Linearity Range	800–2800 ng/spot (R² = 0.9997)
Precision (% RSD)	Intra-day: 0.643–1.391%, Inter-day: 0.212–0.25%
Limit of Detection (LOD)	52.81 ng
Limit of Quantification (LOQ)	160.03 ng

6. Shaheem Sulthana Mohammad and co-workers published the paper in the year 2019. For the development and validation of an analytical method based on UV spectrophotometry for the estimation of Fimasartan in pharmaceutical dosage forms and bulk. For the estimation of Fimasartan in bulk and tablet dosage form, a straightforward, accurate, precise, and economic stability indicating UV spectrophotometric method has been developed. At 261 nm, Fimasartan exhibits the highest λmax. Over a concentration range of 10–50 μg/mL, Beer's law (linearity response) was discovered with a good correlation coefficient (r2 = 0.999). It was discovered that the quantitation limit (QL) was 0.001 mcg/mL and the detection limit (DL) was 0.002 mcg/mL. Fimasartan recovery analysis results ranged from 96.80±0.001 to 98.28±0.002. Fimasartan tablets (Fimanta) had a percentage assay of greater than 99.96%. In accordance with ICH Q1A (R2) guidelines, the suggested spectrophotometric method was validated. Additives and excipients did not interfere with the estimation of Fimasartan in tablet formulation. Therefore, it is safe to use this method for routine quality control analysis of Fimasartan in tablet and bulk dosage form.³⁶

Parameters	Description
Detection Wavelength (λmax)	261 nm
Solvent Used	Methanol
Linearity Range	10–50 µg/mL (R² = 0.999)
Precision (% RSD)	Intra-day: 0.0093–0.0326%, Inter-day: 0.0071–0.0233%
Limit of Detection (LOD)	0.002 µg/mL
Limit of Quantification (LOQ)	0.001 µg/mL
Recovery (%)	96.80–98.28%

7. Sruthi A and co-workers published the paper in the year 2021. For the development and validation of a stability-indicating RP-HPLC analytical method for the estimation of Fimasartan in pharmaceutical dosage forms and bulk. Fimasartan was estimated in bulk and pharmaceutical dosage form using a reverse phase high performance liquid chromatography (RP-HPLC) method that is quick, sensitive, and specific. A Primacel C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) was used for the isocratic RP-HPLC analysis. Acetonitrile and 0.1% orthophosphoric acid were used as the mobile phase, with a v/v ratio of 80:20 and a flow rate of 0.8 ml/min. A UV detector set to 265 nm was used to monitor the analyte. Fimasartan elutes with a typical retention time of 2.4 minutes in the developed method. Fimasartan concentrations using the suggested method range linearly from 5 to 30 μg/ml.³⁷

Parameters	Description
Column Name	Primacel C18 column (150 mm × 4.6 mm, 5 µm)
Mobile Phase	Acetonitrile and 0.1% orthophosphoric acid (80:20 v/v)
Flow Rate	0.8 mL/min
Detection	265 nm
Retention Time	2.4 min
Linearity Range	5–30 µg/mL (R² = 0.9995)
Precision (% RSD)	System Precision: 0.21%, Method Precision: 0.12%
Limit of Detection (LOD)	1.3 µg/mL
Limit of Quantification (LOQ)	4.0 µg/mL
Recovery (%)	99.6–99.7%

8. Chavda Nirma and co-workers published the paper in the year 2022. For stability-indicating RP-HPLC analytical method development and validation for the simultaneous estimation of Rosuvastatin and Fimasartan in a synthetic mixture. Stability indicating RP-HPLC method has been developed for the simultaneous estimation of ROS and FIM in bulk and its pharmaceutical dosage form. In RP-HPLC method, chromatographic separation was achieved using a C18 column (250 mm x 4.6 mm) and Buffer (pH 3.0)-Methanol (60:40) as mobile phase at a flow rate of 1.0 ml/min with detection wavelength of 243 nm. The linearity of ROS was found in the range of 5-15 μg/ml and FIM 30-90 μg/ml. Retention time in RP-HPLC method was found to be 3.9 min and 6.1 min for FIM and ROS respectively. The % recovery was found to be 100.17 ± 7.67 for Rosuvastatin and 100.1± 6.14 for Fimasartan. The proposed method was validated as per ICH guidelines and successfully applied for the determination of drugs in pharmaceutical formulation.³⁸

Parameters	Description
Column Name	C18 column (250 mm × 4.6 mm, 5 µm)
Mobile Phase	Buffer (pH 3.0) and Methanol (60:40 v/v)
Flow Rate	1.0 mL/min
Detection	243 nm
Retention Time	Fimasartan: 3.9 min, Rosuvastatin: 6.1 min
Linearity Range	Fimasartan: 30–90 µg/mL, Rosuvastatin: 5–15 µg/mL
Precision (% RSD)	<2%
Limit of Detection (LOD)	Fimasartan: 0.93 µg/mL, Rosuvastatin: 0.036 µg/mL
Limit of Quantification (LOQ)	Fimasartan: 2.83 µg/mL, Rosuvastatin: 0.11 µg/mL
Recovery (%)	Fimasartan: 99.20–100.72%, Rosuvastatin: 99.27–100.79%

9. Suraj Singh and co-workers published the paper in the year 2022. For UV-Spectrophotometric analytical method development and validation for the simultaneous estimation of Cilnidipine and Fimasartan in a synthetic mixture. This direct spectrophotometric technique relies on the dissolution of Fimasartan and cilnidipine in diluted methanol. The method is based on measurement of absorbance of Cilnidipine and Fimasartan at their respective wavelength of 240nm and 262nm. The maximum absorption wavelength for determination of CIL & FMS drug was found to be at 240 nm and 262 nm. for Beer's law was obeyed in the concentration range from 2 to 10 μg/ml for UV. The regression For both Cilnidipine and Fimasartan Synthetic Mixture, the coefficient values were determined to be y = 0.041x + 0.1351 and y = 0.0337x + 0.3484, respectively, and the correlation coefficients were determined to be 0.9998 and 0.9997 for linearity, range, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), and stability.³⁹

Parameters	Description
Detection Wavelength (λmax)	Cilnidipine: 240 nm, Fimasartan: 262 nm
Solvent Used	Methanol
Linearity Range	2–10 µg/mL for both drugs
Precision (% RSD)	Intra-day: 0.10–0.30%, Inter-day: 0.33–0.71%
Limit of Detection (LOD)	Cilnidipine: 0.8607 µg/mL, Fimasartan: 0.0111 µg/mL
Limit of Quantification (LOQ)	Cilnidipine: 2.6081 µg/mL, Fimasartan: 3.9142 µg/mL
Recovery (%)	99.70–100.36%

10. Aashish Dhaware and co-workers published the paper in the year 2022. For the development and validation of the RP-HPLC analytical method for the simultaneous measurement of chlorthalidone and Fimasartan potassium trihydrate in tablet dosage form. The goal of the current work was to use RP-HPLC to develop and validate a novel, specific, linear, accurate, and precise analytical method for the quantitative estimation of chlorthalidone and Fimasartan potassium trihydrate in tablet dosage form. For this chromatographic analysis, a Prontosil C18 column (250 mm × 4.6 mm, 5μm) was used. The injection volume was 20 μL, and the mobile phase consisted of ACN and potassium phosphate buffer (pH 3) in gradient mode with a flow rate of 1.5 ml/min. Over an 8-minute run time, the detection wavelength was 230 nm. Chlorthalidone and Fimasartan Potassium Trihydrate had respective retention times of 2.6 and 5.0. The above method was validated in accordance with ICH guidelines. Assay results showed that the percentages for Fimasartan Potassium Trihydrate (100.6%) and Chlorthalidone (99.5%) matched the label claims for tablets containing 120 mg and 25 mg of Fimasartan Potassium Trihydrate and Chlorthalidone, respectively. The validation acceptance criteria were met by the two drugs' 0.99 correlation coefficient. Fimasartan Potassium Trihydrate's LOD and LOQ were experimentally determined to be 1.37 and 4.16, respectively, while chlorthalidone's were 0.39 and 1.21.⁴⁰

Parameters	Description
Column Name	Prontosil C18 (250 mm × 4.6 mm, 5 µm)
Mobile Phase	Potassium phosphate buffer (pH 3.0) and Acetonitrile (gradient mode)
Flow Rate	1.5 mL/min
Detection	230 nm
Retention Time	Fimasartan Potassium Trihydrate: 5.0 min, Chlorthalidone: 2.6 min
Linearity Range	Fimasartan: 25–75 µg/mL, Chlorthalidone: 5–15 µg/mL
Precision (% RSD)	System Precision: Fimasartan 0.85%, Chlorthalidone 1.10%
Limit of Detection (LOD)	Fimasartan: 1.37 µg/mL, Chlorthalidone: 0.39 µg/mL
Limit of Quantification (LOQ)	Fimasartan: 4.16 µg/mL, Chlorthalidone: 1.21 µg/mL
Recovery (%)	Fimasartan: 99.93–100.2%, Chlorthalidone: 99.84–100.05%

11. Ritika Gajre and co-workers published the paper in the year 2023. For stability-indicating RP-HPLC analytical method development and validation for the simultaneous estimation of Fimasartan and Chlorthalidone in a synthetic mixture. Fimasartan and chlorthalidone combination medicine used in treatment of hypertension. 254 nm was chosen as the wavelength for quantification. Using a C18 (250 mm x 4.6 mm, 5 um) column and a mobile phase composition of phosphate buffer ph 3.5 adjusted with orthophosphoric acid, acetonitrile, and methanol (30.50.20 v/v/v) at a flow rate of 1 mi/min, the separation was accomplished. Fimasartan's retention period. was 7.12 minutes, and 3.24 minutes for chlorthalidone. According to ICH guidelines, the method was validated. The concentration range of 10–50 ug/ml and 100–500 ug/ml for chlorthalidone showed linearity. Fimasartan and chlorthalidone were found to have correlation coefficients of 0.9952 and 0.9949, respectively. Drug products underwent hydrolysis, H2O2, thermal degradation, and photo degradation as part of the force degradation process. Using the Rp-HPLC method, the percentage of degradation for Fimasartan and chlorthalidone under the specified conditions was found to be between 10 and 20%.⁴¹

Parameters	Description
Column Name	Shimpack ODS C18 (250 mm × 4.6 mm, 5 µm)
Mobile Phase	Phosphate buffer (pH 3.5 adjusted with o-phosphoric acid), Acetonitrile, Methanol (30:50:20 v/v/v)
Flow Rate	1.0 mL/min
Detection	PDA detector at 254 nm
Retention Time	Fimasartan: 7.125 min, Chlorthalidone: 3.249 min
Linearity Range	Fimasartan: 100–500 µg/mL (R² = 0.9949), Chlorthalidone: 10–50 µg/mL (R² = 0.9952)
Precision (% RSD)	Repeatability: 1.18% (Fimasartan), 0.97% (Chlorthalidone)
Limit of Detection (LOD)	Fimasartan: 5.087 µg/mL, Chlorthalidone: 0.865 µg/mL
Limit of Quantification (LOQ)	Fimasartan: 15.43 µg/mL, Chlorthalidone: 2.62 µg/mL
Recovery (%)	Fimasartan: 97.83–102.07%, Chlorthalidone: 98.18–101.57%

7. CONCLUSION:

This review underscores the significant role of analytical methods in evaluating Fimasartan, an angiotensin II receptor blocker used in managing hypertension and cardiovascular disorders. The various chromatographic, spectroscopic, and hyphenated techniques, including HPLC, UPLC, UV-VIS spectroscopy, and LC-MS/MS, have proven invaluable in ensuring the quality, stability, and pharmacokinetic profiling of Fimasartan in bulk drugs and pharmaceutical formulations. However, challenges persist regarding some analytical processes' high costs, complexity, and time-intensive nature. Future trends indicate a promising shift toward automation and green chemistry practices to enhance efficiency, reduce environmental impact, and provide more accessible solutions for Fimasartan analysis. As emerging technologies such as nanotechnology and machine learning-assisted analysis continue to evolve, they hold the potential to revolutionize analytical practices by offering cost-effective, rapid, and highly sensitive methods. Continued research and innovation in these areas will be crucial for addressing current limitations and further advancing pharmaceutical analysis, ensuring Fimasartan's safe and effective use in clinical settings.

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Received on 23.03.2025 Revised on 12.04.2025

Accepted on 28.04.2025 Published on 12.07.2025

Available online from July 21, 2025

Asian Journal of Pharmaceutical Analysis. 2025; 15(3):221-228.

DOI: 10.52711/2231-5675.2025.00035

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