1. INTRODUCTION:

Rosuvastatin (ROS) which is (3R, 5S, 6E)-7-(4-(4-fluorophenyl)- 6-(1-methylethyl)-2-(ethyl(methylsulfonyl) amino)-5-pyrimidinyl)-3,5-dihydroxy-6-heptenoic acid. The mechanism of action of Rosuvastatin calcium is an HMG Co A reductase inhibitor, HMG Co A is a rate-limiting enzyme that converts the 3-hydroxy-3-methylglutarate to mevalonate which is truely precursor of cholesterol synthesis,

Rosuvastatin Calcium with a good and balanced diet helps to reduce LDL (Low density Lipoprotein) which are injuries for our body and helps in preserving the HDL (High density lipoprotein)¹.

Fimasartan potassium trihydrate which is chemically2- (2-butyl-4-methyl-6-oxo-1-{[2′-(1H-1,2,3,4tetrazol-5-yl)- [1,1′-biphenyl]-4-yl]methyl}-1,6-dihydropyrimidin-5-yl)- N,N-dimethylethanethioamide. The mechanism of action of Fimasartan is an angiotensin II receptor antagonist used in the treatment of hypertension and heart failure². Fimasartan is pyrimidin-4(3H)-one derivative of losartan which is produced by replacement of imidazole ring in losartan. Fimasartan has higher potency and longer duration than losartan. Fimasartan was approved in South Korea on September 9, 2010. It is available as a tablet for oral use which contains 60mg or 120mg of Fimasartan potassium trihydrate. Fimasartan is approved in India by CDSCO in 2016.^3,4

The extensive literature review revealed that various methods have been published for the estimation of Rosuvastatin calcium and Fimasartan potassium trihydrate single or in combination with other drugs. Literature review revealed that no method has been developed for simultaneous estimation of ROS and FIM in combined dosage form.^5-9

1.1 Physical and chemical property^10,11:

Rosuvastatin calcium (ROS) is white solid powder. IUPAC name is (E,3R,5S)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5 dihydroxyhept-6-enoic acid. Molecular formula of Rosuvastatin calcium (ROS) is C22H28FN3O6S. Molecular weight is 481.5g/mol. It is Sparingly soluble in water, methanol; slightly soluble in ethanol.

Figure 1: Chemical structure of Rosuvastatin calcium

Figure 2: Chemical Structure of Fimasartan potassium anhydrous

Fimasartan is white to off-white crystalline powder. IUPAC name is 2-(2-Butyl-4-methyl-6-oxo-1-{[2'-(1H-tetrazol-5-yl)-4-biphenylyl]methyl}-1,6-dihydro-5-pyrimidinyl)-N,N-dimethylethanethioamide. Molecular formula of Fimasartan C₂₇H₃₁N₇OS. Molecular weight is 501.65g/mol It is insoluble in water and soluble in ethanol.

1.2 Analytical Method Development^12-16:

Analytical method development and validation assume fundamental part in the drug discovery, drug advancement and assembling the pharmaceutical products. It includes identification of the purity and toxicity of a drug substance. Analytical method development is the process of selecting an accurate assay procedure to determine the composition of a formulation. It is the process of proving that an analytical method is acceptable for use in laboratory to measure the concentration of subsequent samples Analytical methods must be developed using the protocols and acceptance standard arranged in the ICH guidelines Q2(R1). Analytical method development and Validation take part in the discovery, development, and manufacture of pharmaceuticals. The following Literature Survey reveals that there is no any singe method was reported for Rosuvastatin and Fimasartan Combination. However, UV Spectrophotometry, RP–HPLC, HPTLC, Stability indicating RP-HPLC methods, UFLC reported for Rosuvastatin and Fimasartan with other drugs.

2. DRUG PROFILE^17,18:

Table 1 Drug profile of Rosuvastatin and Fimasartan

	Rosuvastatin	Fimasartan
Molecular Weight	481.5g/mol	501.65g/mol
Molecular formula	C22H28FN3O6S	C₂₇H₃₁N₇OS
Drug Category	HMG Co A reductase inhibitor	angiotensin-II receptor antagonist (ARB)
Chemical name	(E,3R,5S)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5 dihydroxyhept-6-enoic acid	2-(2-Butyl-4-methyl-6-oxo-1-{[2'-(1H-tetrazol-5-yl)-4-biphenylyl]methyl}-1,6-dihydro-5-pyrimidinyl)-N,N-dimethyl ethanethioamide
Melting point	156-160°C	>155°C (dec.)
PKa	4.0	4.21
LogP	0.13	4.03
Λmax	252	240 nm
Uses	Antihypertensive and used as a lipid-lowering agent	Antihypertensive

2.1 Mechanism of action of Rosuvastatin (ROS)¹⁹:

Rosuvastatin is a statin drug and a competitive inhibitor of the enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an initiate rate-limiting step in cholesterol biosynthesis. Rosuvastatin behaves primarily in the liver, where reduced hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Rosuvastatin also blocks hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL.

2.2 Mechanism of action of Fimasartan (FIM)²⁰:

Angiotensin II activates AR1 leading to vasoconstriction and increased noradrenaline release which further rises vasoconstriction by action at α1-adrenergic receptors. It also stimulates secretion of aldosterone which acts to rise sodium and water reabsorption in the renal tubules. Fimasartan bind to and antagonizes AR1 blocking vasoconstriction and decreasing aldosterone secretion to rise natriuresis leading to a reduction in blood volume. Together these effects gives an anti-hypertensive effect.

3. LITRETURE REVIEW:

Table 2: Reported Methods for assessment of Fimasartan

Sr. No	Title/Method	Description	Ref. No.
1	UV Spectrophotometric Method Development and Validation of Fimasartan Drug and Its Tablet Formulation	Model: Shimadzu 1800 UV Visible spectrophotometer Solvent: Methanol Wavelength (nm): 240nm Linearity: 2 - 20 µg/ ml	21
2	Stability indicating method development and validation of fimasartan by reverse-phase high-performance liquid chromatography in bulk and pharmaceutical dosage form	Column: Primacel C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) Mobile Phase: Acetonitrile and 0.1% orthophosphoric Acid in 80:20, v/v Flow rate: 0.8 mL/min Wavelength: 240nm Linearity: 5–30 μg/mL Retention Time: 2.4 min	22
3	Validated LC – MS/MS Assay for the Quantitative Determination of Fimasartan in HumanPlasma: Application to Pharmacokinetic Studies	Column: Phenyl-Hexyl column(Lunaw,5mm, 50 mm32.0 mm, Phenomenex) Mobile Phase: A (distilled water with 0.1% formicacid) and mobile phase B (100% acetonitrile with 0.1% formic acid) Flow rate: 0.25 mL/min Wavelength: 240nm Linearity: 0.5 –500 ng/mL Retention Time: 5.6 min	23

Table 3: Reported Methods for assessment of Fimasartan with other drugs

Sr. No	Title/Method	Description	Ref. No.
1	Analytical method development and validation for simultaneous estimation of Fimasartan Potassium Trihydrate and Cilnidipine in synthetic mixture by HPLC for the treatment of hypertension stage-II	Column: Symmetry C18 column (150 mm×4.6 mm, 5 µm) Mobile Phase: Methanol: Methanol: Acetonitrile: Potassium Dihydrogen Phosphate bufer (pH 3) (60:05:35%v/v/v) Flow rate: 1.0 mL/min Wavelength: 240nm Linearity: 15–90 μg/mL and 2.5–15 μg/mL for Fimasartan Potassium Trihydrate and Cilnidipine Retention Time: 2.65 min (FIM) and 5.51 min (CIL).	24
2	Evaluation of stability and simultaneous determination of fimasartan and amlodipine by a HPLC method in combination tablets	Column: Nucleosil C18 column (250 mm 4.6 mm, 5 mm) Mobile Phase: acetonitrile and 0.02 M monopotassium phosphate buffer (pH 2.2) in the ratio of 50:50 (v/v) Flow rate: 1.0 mL/min Wavelength: 237nm Linearity: 6 to 36 mg/ml and 0.5 to 3.0 mg/ml for fimasartan and amlodipine	25
3	Development and validation of novel rp- hplc method for related substances in chlorthalidone and fimasartan formulations	Column: Zodiac C18 (2504.6mm) Mobile Phase: buffer pH 3.0 and 100% methanol in the ratio of 50:50 Flow rate: 1.5 mL/min Wavelength: 240nm Retention Time:* 12.342 min (CHLT) and 32.727 min (FIM)	26
4	Development and validation of a high-performance liquid chromatography-tandem-tandem mass spectrometry for quantitative determination of Fimasartan and Amlodipine in human plasma: Its application to a pharmacokinetic study of 60mg Fimasartan and 10mg Amlodipine	Column: Kinetex C18 (75 × 2.1 mm, 2.6 µm Mobile Phase: 0.05% formic acid- methanol (30:70, v/v) Flow rate: 0.2 mL/min Wavelength: 240nm Linearity: 1-500 ng/mL for Fimasartan and 0.2-20 ng/mL for Amlodipine Retention Time: 1.6 and 1.0 min for Fimasartan and Amlodipine.	27
5	Development of TLC method for simultaneous estimation of novel combination of amlodipine besylate, rosuvastatin calcium, and fimasartan potassium in synthetic mixture	Column: Pre-coated silica gel aluminum plate 60 F254 Mobile Phase: n-hexane, n-butanol, methanol, and Glacial Acetic Acid (5.7:2:2.3:0.1, v/v/v/v) Flow rate: 0.2 mL/min Wavelength: 242nm Linearity: 200-1400 ng/mL (AML), 400-2800 (ROS)and 1200-8400 ng/mL (FIM) Retention Time: 0.21 min (AML), 0.42min (ROS) and 0.7 1.6 min (FIM). regression coefficients (r2 ): 0.9986, 0.9975 and 0.9988 for Amlodipine besylate, Rosuvastatin calcium, and Fimasartan potassium,	28
6	Simultaneous determination of sacubitrilat and fimasartan in rat plasma by a triple quad liquid chromatography-tandem mass spectrometry method utilizing electrospray ionization in positive mode	Column: ACE-5, C₁₈ (4.6 × 50 mm) column Mobile Phase: A (5 mm ammonium formate and 0.1% formic acid in purified water) and B (acetonitrile:methanol, 80:20; v/v) Flow rate: 0.2 mL/min Wavelength: 242nm Linearity: 5 to 10,000 ng/mL	29

Table 4: Official Methods for assessment of Rosuvastatin

Sr No

Official in

Method

Description

Ref. No

IP 2010

(tablet)

RP-HPLC

Column: C18 (25cm × 4.6mm),5 μm

Mobile Phase: Acetate buffer, pH 4.0 acetonitrile: tetrahydrofuran (59:36:5)

Flow rate: 1.5ml/min

Wavelength: 248nm

Table 5: Reported Methods for assessment of Rosuvastatin

Sr. No	Title/Method	Description	Ref. No.
1	Development and Validation of a Stability-Indicating RP-UPLC Method for Determination of Rosuvastatin and Related Substances in Pharmaceutical Dosage Form	Column: Acquity BEH C18 (100 mm × 2.1 mm, 1.7 μm) column Mobile Phase: solvent-A (0.1% trifluoroacetic acid) and solvent-B (methanol). Flow rate: 0.3 mL/min Wavelength: 242nm Linearity: 0.075 to10 μg/mL	31
2	A New Improved RP-HPLC Method for Assay of Rosuvastatin Calcium in Tablets	Column: YMC C8, 150×4.6 mm Mobile Phase: acetonitrile: water (40:60, v/v) pH 3.5 Flow rate: 1.5 mL/min Wavelength: 242nm Linearity: 0.5-80 μg/ml (r²= 0.9993) Run time: 5.2 min	32
3	Stability-indicating method development and validation for the estimation of rosuvastatin calcium in bulk and tablet formulation by reverse-phase high-performance liquid chromatography	Column: Waters Symmetry C18 column with dimensions 150×4.6 mm, 5 mm particle size Mobile Phase: g 0.1% orthophosphoric acid buffer:acetonitrile in the ratio of 55:45% v/v Flow rate: 1.0 mL/min Wavelength: 241nm Linearity: 2-12 µg/ml Retention time: 2.915 min	33
4	Development and validation of a green RP-HPLC method for the analysis of rosuvastatin: a step towards making liquid chromatography environmentally benign	Column: NUCLEODUR 150 mm × 4.6 mm RP C8 column Mobile Phase: ethanol:methanol:ethyl acetate (6:3:1 v/v) Flow rate: 1.0 mL/min Wavelength: 254 nm	34
5	Stability indicating high performance thin layer chromatography method development and validation for estimation of rosuvastatin calcium as bulk drug and in tablet dosage form	Column: precoated silica gel 60 F254 aluminium plates Mobile Phase: mixture of Toluene: Ethyl acetate: Methanol (5: 3: 2, v/v/v) Flow rate: 1.0 mL/min Wavelength: 242nm Linearity: 500-2500 ng band Retention time: 2.553 min (TEL), 4.505 min (ROS)	35
6	A New Simultaneous Determination of Rosuvastatin Calcium and its Lactone Impurity by Reverse Phase HPLC method	Column: sunfire column C18 (250 x 4.6 mm, 5 µm) Mobile Phase: solvent-A (10 mM ammonium acetate) and solvent-B (acetonitrile: methanol (50:50 v/v)) Run time: 15 min Wavelength: 242nm LOD and LOQ: 0.01µg/mL and 0.04µg/Ml	36

Table 6: Reported methods for Rosuvastatin with other drugs combination

	Sr. No	Title/Method	Description	Ref. No.
	1	Development and Validation of Difference Spectrophotometric Method for Simultaneous Estimation of Rosuvastatin Calcium and Aspirin in Marketed Formulation	Solvent: 0.01N acetic acid and 0.01N NaOH Wavelength: 243.2nm and 297nm for RSV ca and ASP Linearity: 10-100µg/m	37
	2	Development and Validation of UV-Spectroscopic First Order Derivative Method for Simultaneous Estimation of Rosuvastatin Calcium and Teneligliptin Hydrobromide Hydrate in Synthetic Mixture	Solvent: Methanol Wavelength: 230nm Linearity: 1-42 µg/ml LOQ: 0.646 µg/ml and 0.3648 µg/ml for rosuvastatin calcium and teneligliptin hydrobromide hydrate LOD: 0.213µg/ml and 0.120 µg/ml for rosuvastatin calcium and teneligliptin hydrobromide hydrate	38
	3	Development and Validation of UV Spectrophotometric Method for The Simultaneous Estimation of Rosuvastatin and Ezetimibe in Pharmaceutical Dosage Form	Solvent: Water Wavelength: 223nm (ROS) and 229nm (EZE) Linearity: 223nm (ROS) and 229nm (EZE) LOD and LOQ: 1.1µg/ml (ROSandEZE) and 3.5µg/ml (ROSandEZE)	39
	4	Development and validation of UV spectrophotometric method for simultaneous estimation of propranolol hydrochloride and rosuvastatin calcium in bulk drug and pharmaceutical dosage form	Solvent: Methanol Wavelength: 223nm (ROS) and 243nm (EZE) Linearity: 2-40 µg/ml for propranolol hydrochloride and 2-42 µg/ml or rosuvastatin calcium	40
5		Development and Validation of Derivative Spectroscopic Method for the Simultaneous Estimation of Rosuvastatin Calcium and Fenofibrate in Tablet	Solvent: Methanol Wavelength: 243nm (ROS) and 224nm (FEN) Linearity: 4-12 µg/ml for Rosuvastatin and 16-48 µg/ml for Fenofibrate LOD andLOQ: 1.96 and 5.96 µg/ml for Rosuvastatin and 0.76 and 2.32 µg/ml for Fenofibrate	41
6		Spectrophotometric Estimation of Rosuvastatin Calcium and Glimepiride in Tablet Dosage Form	Solvent: Methanol Wavelength: 241nm (ROS) and 231nm (GLM) Linearity: 10-22 µg/ml	42
7		Development and Validation of UV Spectrophotometry and RP-HPLC Method for simultaneous determination of Rosuvastin and Clopidogrel in Tablet Dosage Form	Column: C 18 Prontosil Mobile Phase: Methanol:Water 80:20 v/v, pH 3.0 Flow rate: 1.0 mL/min Wavelength: 240nm Linearity: 50-150 µg/ml Retention time: ROSU 3.483min and CLOP 4.983min Tailing factor:1.1787 (ROS) and 1.074 (CLOP)	43
8		Stability-indicating RP-HPLC method development and validation for simultaneous estimation of telmisartan and rosuvastatin calcium in bulk and in tablet dosage form	Column: column Oyster ODS3 (150×4.6 mm, 5 µm) Mobile Phase: 10 mM phosphate bufer with 1.1 g octane-1-sulfonic acid sodium salt having pH 2.5 (adjusted with 5% OPA) and acetonitrile, with a proportion of 500:500, v/v Flow rate: 1.0 mL/min Wavelength: 242nm Linearity: 99.9073 to 299.7218 µg/mL for telmisartan (R2=1.000) and 23.6841 – 71.0522 µg/mL for rosuvastatin (R2=0.999. Retention time: 2.553 min (TEL), 4.505 min (ROS)	44
9		RP_HPLC method development and validation for the simultaneous estimation of Rosuvastatin and Ezetimibe in tablet dosage form	Column: Symmetry X-terra C8 (4.6mm x 100mm, 5mm)column Mobile Phase: ortho phosphoric acid buffer and Acetonitrile in the ratio 40:60 v/v Flow rate: 1.0 mL/min Wavelength: 237nm Linearity: 10–50 μg mL Retention time: 2.490 min (ROS), and 3.173 min (EZE)	45
10		Analytical Method Development and Validation for the Simultaneous Estimation of Aspirin, Clopidogrel and Rosuvastatin in Pharmaceutical Dosage Form	Column: Hypersil BDS C18 column (250 mm ×4.6, 5 μm) Mobile Phase: KH2Po4 buffer pH-6.0: acetonitrile in the ratio 60:40 Flow rate: 1.0 mL/min Wavelength: 242nm Linearity: 7.5-22.5μg/ml and 1-3μg/ml for CLOP, ASP and ROS respectively. Retention time: ASP, CLOP and ROS was found to be 3.103 min, 4,277 min and 5.707 min respectively	46
11		Analytical method development and validation for the simultaneous estimation of Rosuvastatin and Finofibate in tablet dosage form by reverse phase high performance liquid chromatography	Column: Hypersil C18 (4.6 x 250mm, 6.5 mm, Make: Waters) Mobile Phase: OPA buffer (pH 3.0): Methanol (65:35%v/v) Flow rate: 1.2 mL/min Wavelength: 238 nm Linearity: 50 µg/mL to 150 µg/mL for ROS and 50 µg/mL to 150 µg/mL for FEN Retention time: 1.950 and 3.858 minutes for ROS and FEN	47
12		Development and Validation of a Stability-indicating RP-HPLC Method for Estimation of Metformin and Rosuvastatin along with Impurities from a Combined Oral Solid Dosage Form	Column: Hypersil C18 (4.6 x 250mm, 6.5 mm, Make: Waters) YMC-Pack ODS-A 100×4.6 mm; 3 µm column Mobile Phase: 20 mM ammonium acetate:acetonitrile (9:1 v/v) pH 3.5, and mobile phase B, consisted of 20 mM ammonium acetate:acetonitrile:methanol (3:5:2 v/v/v) pH 3.5. Flow rate: 0.9 mL/min Wavelength: 240 nm	48
13		Development and Validation of a Reversed-phase High Performance Liquid Chromatography Method for the Simultaneous Estimation of Rosuvastatin Calcium andTelmisartan in Fixed-Dose Complex Dual-Layer Tablets in Six Dosage Forms	Column: Kinetex C18 (5 µm, 4.6×150 mm) columns Mobile Phase: ammonium phosphate monobasic buffer (pH 3.0) and methanol at a ratio of 300:700 Flow rate: 1.0 mL/min Wavelength: 242 nm Linearity: 4.44-26.6 µg/ml (ROS) and 0.176-106.6 µg/ml (TEL) Retention time: rosuvastatin calcium and telmisartan were 2.2 and 4.3 min	49
14		Development and validation of a RP-HPLC-PDA method for simultaneous determination of Rosuvastatin calcium and Amlodipine besylate in pharmaceutical dosage form	Column: Kromasil C18 (5 micron 4.6 × 250mm) and Qualisil C8 (5 micron 4.6 × 250mm) Mobile Phase: methanol and acetonitrile (pH 3.5 adjusted by ortho- phosphoric acid) (60:40 v/v) Flow rate: 1.0 mL/min Wavelength: 251nm Linearity: ROSUVASTATIN AND AMLODIPINE were made from 1.0 to 160 µg/ml and 0.5 to 80 µg/ml, Retention time: 3.7 min (AMLO), 5.4 min (ROS)	50
15		Development and validation of novel RP-HPLC method for the simultaneous determination of Rosuvastatin and Teneligliptin in bulk and in synthetic mixture	Column: Luna C18 100A0(250mm×4.6mm Flow rate: 1.0 mL/min Wavelength: 240nm Linearity: 10-200µg/ml for Teneligliptin and 10-200µg/ml for Rosuvastatin. Retention Time: Teneligliptin and Rosuvastatin were 2.583 and 5.458 min	51
16		Simultaneous determination of rosuvastatin and atorvastatin in human serum using RP-HPLC/UV detection: Method development, validation and optimization of various experimental parameters	Column: Brownlee analytical C18 column (150 × 4.6 mm, 5 μm) Mobile Phase: methanol–water (68:32, v/v; pH adjusted to 3.0 with trifluoroacetic acid) Flow rate: 1.5 mL/min Wavelength: 241nm Linearity: 2.0–256 ng/ml for rosuvastatin and 3.0–384 ng/ml for atorvastatin	52
17		Development and validation of hptlc method for simultaneous estimation of rosuvastatin calcium and aspirin in capsule dosage form	Column: precoated silica gel 60 F254 Mobile Phase: f n-Hexane: Acetone: Ethyl acetate: Formic acid (6:3:1:0.2 v/v) Flow rate: 1.0 mL/min Wavelength: 240nm Linearity: 500- 1000 ng/spot and 3750-7500 ng/spot for Rosuvastatin calcium and Aspirin	53
18		RP-HPLC Method Development and Validation for Simultaneous Estimation of Telmisartan, Rosuvastatin Calcium and Amlodipine Besylate in Combination	Column: Luna C18 100Å column (250 mm × 4.6 mm i.d., particle size 5 μ) Mobile Phase: methanol and acetonitrile (pH 3.5 adjusted by ortho- phosphoric acid) (60:40 v/v) Flow rate: 1.0 mL/min Wavelength: 242nm Linearity: 40-200 µg/ml for TEL, 10-50 µg/ml for ROS, and 5-25 µg/ml for AML. Retention time: 2.67 min (TEL), 4.70 min (ROS), and 7.44 min (AML)	54
19		Development and Validation of Stability-Indicating HPLC Methods for Quantitative Determination of Pravastatin, Fluvastatin, Atorvastatin, and Rosuvastatin in Pharmaceuticals	Column: RP-18 column Mobile Phase: methanol–water (60:40, v/v, for PS and RC and 70:30, v/v, for FVS and ATC) Flow rate: 1.0 mL/min Wavelength: 242nm LOD andLOQ:1.22 and 3.08 µg/mL for PS, 2.02 and 6.12 µg/mL for FVS, 0.44 and 1.34 µg/mL for ATC, and 1.55 and 4.70 µg/mL for RC	55
20		Development and validation of stability-indicating rp-hplc method for simultaneous estimation of rosuvastatin and glibenclamide	Column: C18 (ZORBAX Eclipse Plus 4.6 mm×150 mm, 5μm) Mobile Phase: methanol: acetonitrile: 0.02 M phosphate buffer pH 3.5 (60:20:20 v/v/v) Flow rate: 1.0 mL/min Wavelength: 237nm Linearity: 5-22 µg/ml	56
21		An LC–MS/MS spectrometry method for the simultaneous determination of Rosuvastatin and Irbesartan in rat plasma: Insight into pharmacokinetic and drug-drug interaction studies	Column: Agilent Eclipse Plus ODS (4.6 × 100 mm, 3.5 μm) column Mobile Phase: 6 mM ammonium formate/0.1% formic acid Flow rate: 0.4 mL/min	57
22		Simultaneous Determination of Prazosin, Atorvastatin, Rosuvastatin and Simvastatin in API, Dosage Formulations and Human Serum by RP-HPLC	Column: nucleosil 100-10, C-18, 10μ column having 250 × 4.6 mm Mobile Phase: methanol:water:acetonitrile (70:20:10) adjusted to pH 2.5 ± 0.02 using orthophosphoric acid Wavelength: 240nm	58

4. CONCLUSION:

This review article presents with Physico-chemical properties and Pharmacological actions of Rosuvastatin and Fimasartan. The presented review depicts the information about the various methods available in the literature for the determination of Rosuvastatin and Fimasartan including official pharmacopeial assay methods. According to this review it was concluded that the different analytical methods are reported for estimation Rosuvastatin and Fimasartan. individual and other combination like UV Spectroscopy, HPTLC, HPLC, LC-MS. Hence all methods found to be simple, accurate, economic, precise and reproducible in nature. Most of Methods were of RP-HPLC and UV Spectrophotometric methods because these methods provided with best available reliability, repeatability, analysis time and sensitivity. The given Literature review focus that there is no methods are reported for Rosuvastatin and Fimasartan in fixed dose combination. This review will help in future to develop the analytical methods for this new combination and also gives the knowledge about its characteristics of both drugs.

5. CONFLICT OF INTEREST:

The authors declare no conflict of interest.

6. ABBREVIATIONS:

ROS, Rosuvastatin; HMG Co A, β-Hydroxy β-methylglutaryl-CoA; LDL, Low density Lipoprotein; HDL, High density lipoprotein; FIM, Fimasartan; CDSCO, Central Drugs Standard Control Organisation; ICH, International Council for Harmonisation; HPLC, High-performance liquid chromatography; HPTLC, High-performance thin-layer chromatography; UPLC, Ultra-performance liquid chromatography; UV, Ultraviolet; UFLC, ultra performance/fast liquid chromatography; LC-MS, Liquid chromatography-mass spectrometry.

7. REFERENCES:

1. https://www.drugbank. ca/drugs/DB01098. Accessed 10 July2019. (Drug Bank (2019) Rosuvastatin Calcium).

2. https:// www.drugbank.ca/drugs/DB09279. Accessed 9 July 2019 (Drug Bank (2019) Fimasartan potassium trihydrate).

3. Kansara, D.A, Chhalotiya, U.K, Kachhiya, H.M. Simultaneous estimation of amlodipine besylate, Rosuvastatin calcium and Fimasartan potassium trihydrate combination used in the treatment of hypertension using LC method. SN Appl. Sci. 2.

4. Charu P. Pandya1 and Sadhana J. Rajput. Separation and characterization of major oxidative impurity in fimasartan drug substance. Rasayan J. Chem. 2018; 11(3): 1042-1049 http://dx.doi.org/10.31788/RJC.2018.1132083.

5. M. Girija, N. Kokilavani. Effectiveness of Structured Teaching Programme on Knowledge, Attitude and Practice among Patients with Hypertension. Asian J. Nur. Edu. and Research. 2014; 4(1): 136-139.

6. Devi. S, L N Samaga. Effect of transcendental meditation on stress and blood pressure among patients with systemic hypertension. Asian J. Nur. Edu. and Research. 2015; 5(1): 151-156.

7. Suraj V. Bondre, Rushikesh S. Chavan, Indrayani D. Raut, Shrinivas K. Mohite, Chandrakant S. Magdum. An Overview of Survey on Antihypertensive Drugs. Asian J. Pharm. Res. 2020; 10(3):160-162.

8. V.V. Karkhanis, Vikas Parikh, Roma Panchal. Estimation of Rosuvastatin Calcium in Tablet Dosage Form by HPTLC Method. Asian J. Research Chem. 2011; 4(8): 1206-1209.

9. ICH harmonized tripartite guideline: Stability testing of new drug substances and products, Q1A(R2). International Conference on Harmonization, Geneva. 2003:1-24.

10. https://go.drugbank.com/drugs/DB09279.

11. ICHQ2(R1): Validation of Analytical Procedure. Text and Methodology. International Conference on Harmonization. IFPMA. Geneva, Switzerland, 2005.

12. Nirma Chavda, Suresh Kumar. A Review article on Analytical Method Development for the combination of Azelnidipine and Telmisartan. Asian Journal of Pharmaceutical Analysis. 2021; 11(3):227-4.

13. Hamid Khan. Analytical Method Development in Pharmaceutical Research: Steps involved in HPLC Method Development. Asian J. Pharm. Res. 2017; 7(3): 203-207.

14. Chinmaya Keshari Sahoo, Muvvala Sudhakar, D. Venkata Ramana, K. Satyanarayana, Kanhu Charan Panda. Validation of Analytical Procedures- A Review. Asian J. Pharm. Ana. 2018; 8(2): 109-116.

15. Praful Sahare, Amit Nayak, Alok Pal Jain, Harikishor Barange. Development of Validated Analytical Methods and Stability Indicating studies for Pharmaceutical Formulation. Asian J. Pharm. Ana. 2021; 11(1):29-37.

16. https://pubchem.ncbi.nlm.nih.gov/compound/Rosuvastatin. National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 446157, Rosuvastatin. Retrieved September 5, 2022.

17. https://pubchem.ncbi.nlm.nih.gov/compound/Fimasartan. National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 9870652, Fimasartan. Retrieved September 5, 2022 from

18. https://go.drugbank.com/drugs/DB01098.

19. Rang, H. P, Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.), Edinburgh: Elsevier/Churchill Livingstone. (ISBN 978-0-7020-3471-8).

20. Kim JH, Lee JH, Paik SH, Kim JH, Chi YH. Fimasartan, a novel angiotensin II receptor antagonist. Arch Pharm Res. 2012 Jul;35(7):1123-6. doi: 10.1007/s12272-012-0700-z. (PubMed ID 22864732).

21. Agrawal KS, Gandhi LR, Bhajipale NS. UV Spectrophotometric Method Development and Validation of Fimasartan Drug and Its Tablet Formulation. Asian Journal of Pharmaceutical Research and Development. 2019; 7(5): 26-30.

22. Sruthi a, uttam prasad panigrahy. Stability indicating method development and validation of fimasartan by reverse-phase high-performance liquid chromatography in bulk and pharmaceutical dosage form. Asian J Pharm Clin Res. 2021; 14(2): 138-14.

23. Seo Hyun Yoon, Seul Oh, Hwa Suk Kim, SoJeong Yi, Kyung-Sang Yu, In-Jin Jang, Joo-Youn Cho. Validated LC–MS/MS Assay for the Quantitative Determination of Fimasartan in Human Plasma: Application to Pharmacokinetic Studies. Journal of Chromatographic Science. 2015; 53(8): 1250–1256. https://doi.org/10.1093/chromsci/bmu219

24. Radhika G. Sojitra, Urvi J. Chotaliya. Analytical method development and validation for simultaneous estimation of Fimasartan Potassium Trihydrate and Cilnidipine in synthetic mixture by HPLC for the treatment of hypertension stage-II. Futur J Pharm Sci. 2021; 7:189.

25. Hyeon Woo Moon, Abid Mehmood Yousaf, Kwan Hyung Cho, Chul Soon Yong, Jong Oh Kim, Han-Gon Choi. Evaluation of stability and simultaneous determination of fimasartan and amlodipine by a HPLC method in combination tablets. Asian Journal of Pharmaceutical Sciences. 2014; 9(3):123-128.

26. Kritika Rai1 and Dr. Nutan Rao. Development and validation of novel rp- hplc method for related substances in chlorthalidone and fimasartan formulations. World Journal of Pharmaceutical Research. 2020; 9(4).

27. Do-Hyung Kim, Jeong-Hun Lee, Wang-seob Shim and Kyung-Tae Lee. Development and validation of a high-performance liquid chromatography-tandem-tandem mass spectrometry for quantitative determination of Fimasartan and Amlodipine in human plasma: Its application to a pharmacokinetic study. Journal of Pharmaceutical Care and Health System.

28. Devansh Kansara, Usmangani K. Chhalotiya, Hetaben M. Kachhiya and Ishita Patel. Development of TLC method for simultaneous estimation of novel combination of amlodipine besylate, rosuvastatin calcium, and fimasartan potassium in synthetic mixture. J. Chem. Metrol. 2020; 14.

29. Giri P, Joshi V, Giri S, Delvadia P, Jain MR. Simultaneous determination of sacubitrilat and fimasartan in rat plasma by a triple quad liquid chromatography-tandem mass spectrometry method utilizing electrospray ionization in positive mode. Biomed Chromatography. 2021; 35(2): e4981. doi: 10.1002/bmc.4981. Epub 2020 Sep 18. PMID: 32895916.

30. Indian Pharmacopeia 2010. Indian Government Health and Welfare Society. Ghaziabad. 2072-2073.

31. Trivedi HK, Patel MC. Development and Validation of a Stability-Indicating RP-UPLC Method for Determination of Rosuvastatin and Related Substances in Pharmaceutical Dosage Form. Sci Pharm. 2012; 80(2): 393-406. doi: 10.3797/scipharm.1201-09. Epub 2012 Mar 26. PMID: 22896825; PMCID: PMC3383219.

32. Kaila HO, Ambasana MA, Thakkar RS, Saravaia HT, Shah AK. A New Improved RP-HPLC Method for Assay of Rosuvastatin Calcium in Tablets. Indian J Pharm Sci. 2010; 72(5): 592-8. doi: 10.4103/0250-474X.78526. PMID: 21694991; PMCID: PMC3116304.

33. Sailaja B, Sravana Kumari K. Stability-indicating method development and validation for the estimation of rosuvastatin calcium in bulk and tablet formulation by reverse-phase high-performance liquid chromatography. Asian J Pharm Clin Res. 2019; 12(8): 251-256.

34. Nazrul Haq, Faiyaz Shakeel, Fars Alanazi, Doaa H. Alshora and Mohamed Abbas Ibrahim. Development and validation of a green RP-HPLC method for the analysis of rosuvastatin: a step towards making liquid chromatography environmentally benign. Green Process Synth. 2018; 7: 160–169.

35. Dipak R Supe, Padmanabh B. Deshpande, Saurabh Jadhav and Sandeep Swami. Stability indicating high performance thin layer chromatography method development and validation for estimation of rosuvastatin calcium as bulk drug and in tablet dosage form. European Journal of Biomedical and Pharmaceutical Sciences. 2021; 8(9).

36. Prabhu Venkatesh Moodbidri, Varadaraji Dhayanithi, Ganesh Belavadi Manjunathashastry, Hari Narayan Pati, Pardhasaradhi Vasireddy. A New Simultaneous Determination of Rosuvastatin Calcium and its Lactone Impurity by Reverse Phase HPLC method. Asian J. Pharm. Res. 2015; 5(4): 175-182.

37. Padmavathi, R, Padmavathi, Y, Babu, N, Akhila, V, and Keerthi, G. Development and Validation of Difference Spectrophotometric Method for Simultaneous Estimation of Rosuvastatin Calcium and Aspirin in Marketed Formulation. Asian Journal of Pharmaceutical Research and Development. 2021; 9(6): 56-61. https://doi.org/https://doi.org/10.22270/ajprd.v9i6.1046.

38. Vyas, A, Godhaniya, J, Patel, A, Patel, A, Patel, N, Shah, S and Sheth, D. (2021). Development and Validation of UV-Spectroscopic First Order Derivative Method for Simultaneous Estimation of Rosuvastatin Calcium and Teneligliptin Hydrobromide Hydrate in Synthetic Mixture. Chemical Methodologies. 2021; 5(4): 317-323. doi: 10.22034/chemm.2021.131260.

39. Sireesha. D, M. Laksmi Monika, Vasudha Bakshi. Development and Validation of UV Spectrophotometric Method for The Simultaneous Estimation of Rosuvastatin and Ezetimibe in Pharmaceutical Dosage Form. Asian J. Pharm. Ana. 2017; 7(3): 135-140. doi: 10.5958/2231-5675.2017.00021.7.

40. Namdeo G. Shinde and Nagesh H. Aloorkar. Development and validation of UV spectrophotometric method for simultaneous estimation of propranolol hydrochloride and rosuvastatin calcium in bulk drug and pharmaceutical dosage form. International Journal of Advances in Pharmaceutics. 2015; 4(5) DOI: 10.7439/ijap.

41. Bhavna Patel, Alpa Jadav, Heena Solanki, Shraddha Parmar, Vijay Parmar, Anadikumari Captain. Development and Validation of Derivative Spectroscopic Method for the Simultaneous Estimation of Rosuvastatin Calcium and Fenofibrate in Tablet. International Journal of Pharma Research and Review. 2013; 2(7):1-6.

42. Afroz Asma, Haque Tasnuva, Md. Talukder Mesbah Uddin, Islam S. M. Ashrafu, Spectrophotometric Estimation of Rosuvastatin Calcium and Glimepiride in Tablet Dosage Form. Asian Journal of Pharmaceutical Analysis. 2011; 1(4): 74-78.

43. Roshan Telrandhe. Development and Validation of UV Spectrophotometry and RP-HPLC Method for simultaneous determination of Rosuvastin and Clopidogrel in Tablet Dosage Form. Asian J. Pharm. Ana. 2018; 8(1): 25-32.

44. Gholve, R, Pekamwar, S, Wadher, S. Stability-indicating RP-HPLC method development and validation for simultaneous estimation of telmisartan and rosuvastatin calcium in bulk and in tablet dosage form. Futur J Pharm Sci. 2021; 7: 224. https://doi.org/10.1186/s43094-021-00369-2

45. Rajeswar Dutt, Kunduri. RP_HPLC method development and validation for the simultaneous estimation of Rosuvastatin and Ezetimibe in tablet dosage form. International Journal of Pharmacy and Analytical Research. 2014; 3: 13-21.

46. Tiwari, Pradip and Jain, Amit and Dubey, BK and Pandey, GK and Dhakad, Suresh. Analytical Method Development and Validation for the Simultaneous Estimation of Aspirin, Clopidogrel and Rosuvastatin in Pharmaceutical Dosage Form. Journal of Drug Delivery and Therapeutics. 2019; 9: 432-438. 10.22270/jddt.v9i4-s.3351.

47. M. Sumalatha, K. Haritha Pavani. Analytical method development and validation for the simultaneous estimation of Rosuvastatin and Finofibate in tablet dosage form by reverse phase high performance liquid chromatography. Indian Journal of Research in Pharmacy and Biotechnology.

48. D. Sangeetha and M. K. Vadlamudi. Development and Validation of a Stability-indicating RP-HPLC Method for Estimation of Metformin and Rosuvastatin along with Impurities from a Combined Oral Solid Dosage Form. Indian J Pharm Sci. 2019; 81(2): 365-372. DOI: 10.36468/pharmaceutical-sciences.518.

49. Min Nyeong Choi, Y. J. Park and Joo Eun Ki. Development and Validation of a Reversed-phase High Performance Liquid Chromatography Method for the Simultaneous Estimation of Rosuvastatin Calcium and Telmisartan in Fixed-Dose Complex Dual-Layer Tablets in Six Dosage Forms. Indian J Pharm Sci. 2021; 83(3): 451-464, DOI: 10.36468/pharmaceutical-sciences.794.

50. Dipali Tajane, Amol M. Raurale, Pradeep D. Bharande, Anil N. Mali, Amol V. Gadkari, Vishal R. Bhosale. Development and validation of a RP-HPLC-PDA method for simultaneous determination of Rosuvastatin calcium and Amlodipine besylate in pharmaceutical dosage form. Journal of Chemical and Pharmaceutical Research. 2012; 4(5): 2789-2794.

51. Padmavathi, R, Padmavathi, Y, Babu, N, Akhila, V, and Keerthi, G. Development and Validation of Difference Spectrophotometric Method for Simultaneous Estimation of Rosuvastatin Calcium and Aspirin in Marketed Formulation. Asian Journal of Pharmaceutical Research and Development. 2021; 9(6): 56-61. https://doi.org/https://doi.org/10.22270/ajprd.v9i6.1046.

52. Drashti A. Mandale, Chainesh Shah, Rakesh Jatt. Development and validation of novel RP-HPLC method for the simultaneous determination of Rosuvastatin and Teneligliptin in bulk and in synthetic mixture. International Journal of Pharmaceutical Research.

53. Dipak R Supe, Padmanabh B. Deshpande, Saurabh Jadhav and Sandeep Swami. Stability indicating high performance thin layer chromatography method development and validation for estimation of rosuvastatin calcium as bulk drug and in tablet dosage form. European Journal of Biomedical and Pharmaceutical Sciences. 2021; 8(9).

54. Vyas, A, Godhaniya, J., Patel, A, Patel, A, Patel, N, Shah, S and Sheth, D. Development and Validation of UV-Spectroscopic First Order Derivative Method for Simultaneous Estimation of Rosuvastatin Calcium and Teneligliptin Hydrobromide Hydrate in Synthetic Mixture. Chemical Methodologies. 2021; 5(4): 317-323. doi: 10.22034/chemm.2021.131260.

55. Pallavi H. Tank, K. R. Vadalia, Z. R. Dedania. Development and validation of hptlc method for simultaneous estimation of rosuvastatin calcium and aspirin in capsule dosage form. Tank et al. IJPSR. 2012; 3(10): 3867-3870.

56. Rujuta P. Mistry, Chainesh Shah, Rakesh Jat. RP-HPLC Method Development and Validation for Simultaneous Estimation of Telmisartan, Rosuvastatin Calcium and Amlodipine Besylate in Combination. Folia Medica. 2022; 64(1):103-9 DOI: 10.3897/folmed.64.e64339.

57. R. Dastaran, A. Sheibani, M. Reza Shishehbore, H. Saeedi-Sourck. Continuous Wavelet Transform for Simultaneous Determination of Atorvastatin and Rosuvastatin in Combined Pharmaceutical Formulations. Journal of Applied Spectroscopy. 2022; 88(6): 1195-1201. 10.1007/s10812-022-01299-4 .

58. Najma Sultana, M. Saeed Arayne, Shabana Naz Shah, Nighat Shafi, Safila Naveed. Simultaneous Determination of Prazosin, Atorvastatin, Rosuvastatin and Simvastatin in API, Dosage Formulations and Human Serum by RP-HPLC. Journal of the Chinese Chemistry Society. 2010; 57(6): 1286-1292.

Received on 28.09.2022 Modified on 08.11.2022

Asian J. Pharm. Ana. 2023; 13(3):197-204.

DOI: 10.52711/2231-5675.2023.00032

Simultaneous determination of sacubitrilat and fimasartan in rat plasma by a triple quad liquid chromatography-tandem mass spectrometry method utilizing electrospray ionization in positive mode

Development and Validation of a Stability-Indicating RP-UPLC Method for Determination of Rosuvastatin and Related Substances in Pharmaceutical Dosage Form

A New Improved RP-HPLC Method for Assay of Rosuvastatin Calcium in Tablets

Stability-indicating method development and validation for the estimation of rosuvastatin calcium in bulk and tablet formulation by reverse-phase high-performance liquid chromatography

Development and validation of a green RP-HPLC method for the analysis of rosuvastatin: a step towards making liquid chromatography environmentally benign

Stability indicating high performance thin layer chromatography method development and validation for estimation of rosuvastatin calcium as bulk drug and in tablet dosage form

Development and Validation of Difference Spectrophotometric Method for Simultaneous Estimation of Rosuvastatin Calcium and Aspirin in Marketed Formulation

Development and Validation of UV-Spectroscopic First Order Derivative Method for Simultaneous Estimation of Rosuvastatin Calcium and Teneligliptin Hydrobromide Hydrate in Synthetic Mixture

Development and Validation of UV Spectrophotometric Method for The Simultaneous Estimation of Rosuvastatin and Ezetimibe in Pharmaceutical Dosage Form

Development and validation of UV spectrophotometric method for simultaneous estimation of propranolol hydrochloride and rosuvastatin calcium in bulk drug and pharmaceutical dosage form

Development and Validation of Derivative Spectroscopic Method for the Simultaneous Estimation of Rosuvastatin Calcium and Fenofibrate in Tablet

Spectrophotometric Estimation of Rosuvastatin Calcium and Glimepiride in Tablet Dosage Form

RP_HPLC method development and validation for the simultaneous estimation of Rosuvastatin and Ezetimibe in tablet dosage form

Analytical Method Development and Validation for the Simultaneous Estimation of Aspirin, Clopidogrel and Rosuvastatin in Pharmaceutical Dosage Form

Analytical method development and validation for the simultaneous estimation of Rosuvastatin and Finofibate in tablet dosage form by reverse phase high performance liquid chromatography

Development and Validation of a Stability-indicating RP-HPLC Method for Estimation of Metformin and Rosuvastatin along with Impurities from a Combined Oral Solid Dosage Form

Development and Validation of a Reversed-phase High Performance Liquid Chromatography Method for the Simultaneous Estimation of Rosuvastatin Calcium andTelmisartan in Fixed-Dose Complex Dual-Layer Tablets in Six Dosage Forms

Development and validation of a RP-HPLC-PDA method for simultaneous determination of Rosuvastatin calcium and Amlodipine besylate in pharmaceutical dosage form

Development and validation of novel RP-HPLC method for the simultaneous determination of Rosuvastatin and Teneligliptin in bulk and in synthetic mixture

Simultaneous determination of rosuvastatin and atorvastatin in human serum using RP-HPLC/UV detection: Method development, validation and optimization of various experimental parameters

Development and validation of hptlc method for simultaneous estimation of rosuvastatin calcium and aspirin in capsule dosage form

An LC–MS/MS spectrometry method for the simultaneous determination of Rosuvastatin and Irbesartan in rat plasma: Insight into pharmacokinetic and drug-drug interaction studies

Simultaneous Determination of Prazosin, Atorvastatin, Rosuvastatin and Simvastatin in API, Dosage Formulations and Human Serum by RP-HPLC