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International journal of Applied Pharmaceutical and Biological Research, 2017; 2(2):11-27

Research Article ISSN : 2456-0189

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STABILITY INDICATING NEW RP-HPLC METHOD FOR THE

DETERMINATION OF ROSUVASTATIN CALCIUM IN PURE AND TABLETS

DOSAGE FORMS

Mohamed El-Kassem M Hassouna*, Hafsa Omar Salem

Chemistry Department, Faculty of Science 62514, Beni-Suef University, Beni-Suef , Egypt

ABSTRACT

A new, specific, precise, simple, and accurate RP-HPLC method is developed and validated for the determination of Rosuvastatin calcium (ROS-Ca) in pure and tablets dosage forms. The method is performed on the Agilent Eclipse XDB C8 column (250 mm X 4.6 mm, 5μm particle size, using buffer solution of pH 4.5 containing 0.05M sodium dihydrogen phosphate: acetonitrile (50:50 v/v) as the mobile phase at a flow rate of 1.2 mL/min, injection volume 10 µL and UV detection at 245 nm. The total run time is 5.0 min. Linear relationship are obtained in the range 5-100 µg/mL and Rt values of 3.684 min for ROS-Ca with correlation coefficient (r) = 0.9995, limit of detection 1.50 µgmL-1 and limit of quantitation is 4.56 µgmL-1 for ROS-Ca. The overall recovery is 100 ± 2 % ; the relative standard deviation for precision and intraday precision is less than 2.0 %. Also, the forced degradation studies as acidity, alkalinity, oxidation, heat and photo degradation are performed according to ICH guidelines. The method is validated according to ICH guidelines and USP requirements for new methods, which include accuracy, precision, specificity, LOD, LOQ, robustness, ruggedness, linearity and range. Hence this RP-HPLC method is suitable for quality control of raw materials and finished products.

Key words: Rosuvastatin Calcium; Stability; Assay; tablets dosage form; ICH; USP; HPLC

INTRODUCTION

Rosuvastatin Calcium (ROS-Ca); is chemically known as [(3R,5S,6E)-7-[4-(4-fluorophenyl)-6-(1-

methyleythyl) -2- [methyl (methyl sulfonyl) amino] pyrimidine-5- yl]-3,5-dihydroxyhept-6-enoate]. It has a

molecular formula of C44H45CaF2N6O12S2 and a molecular weight of 1001 [1, 2]. (Fig 1).

Rosuvastatin Calcium is a white or almost white, hygroscopic powder, slightly soluble in water, freely soluble in methylene chloride, practically insoluble in anhydrous ethanol. Store in airtight container, protected from

light, at temperature of 2°C to 8°C.[1,2].

Rosuvastatin is available in tablet form containing 5 mg, 10 mg, 20 mg and 40 mg of the active ingredient,

Rosuvastatin calcium. The excipients are: microcrystalline cellulose NF, lactose monohydrate NF, tribasic

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M. Hassouna et al IJAPBR, 2017; 2(2):11-27

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calcium phosphate NF, crospovidone NF, magnesium stearate NF, hypromellose NF, triacetin NF, titanium

dioxide USP, yellow ferric oxide, and red ferric oxide NF. [3].

Figure 1: Chemical structures of Rosuvastatin Calcium.

Rosuvastatin selectively and competitively inhibits HMG-CoA reductase, the rate-limiting enzyme that

converts HMG-CoA to mevalonate, a precursor of cholesterol. Rosuvastatin has been shown to have high

uptake and selectivity in the liver, the target organ for cholesterol lowering. Rosuvastatin produces its lipid-modifying effects in two ways: it increases the number of hepatic LDL receptors on the cell-surface to

enhance the uptake and catabolism of LDL, and it inhibits hepatic synthesis of VLDL, which reduces the total

number of VLDL and LDL particles [3].

Literature review revealed that various analytical methods have been described for the determination of

Rosuvastatin Calcium including spectrophotometric [4-15], thin layer chromatography (TLC) [16], capillary

electrophoresis [17],mass spectrometry [18-24],liquid chromatography (HPLC, UPLC)[25–50],

electrochemical methods [51,52] and complexometric titration [53] have been developed for the estimation

of ROS-Ca in pure or in dosage forms.

The aim of the present work is to develop a new, simple, sensitive, short retention time and accurate RP-HPLC

method for the determination of ROS-Ca in pure or in dosage forms and application to assay dosage forms

with high sensitivity, selectivity that are required to be in routine quality control analysis and validate the

developed methods according to ICH guidelines [54].

MATERIALS AND METHOD

Chemicals and Reagents

Acetonitrile, Methanol HPLC-grade, Sodium dihydrogen phosphate monohydrate analytical grade,

Triethylamine HPLC grade, Hydrochloric Acid analytical grade, Sodium Hydroxide reagent grade and distilled Water are procured from (scharlau, Spain).

Pure samples

Pure samples of Rosuvastatin Calcium were kindly supplied by SPIMACO Pharmaceutical Company,

Alexandria, Egypt with claimed purity of 100.5%. The content of Rosuvastatin Calcium in BP Pharmacopeia is

in the range 97.0 to 102.0 percent.

Pharmaceutical dosage form

Six pharmaceutical preparations viz., Cholerose 10 mg Tab, Crestore 10 mg Tab, Estero-map 10 mg Tab, Advochol 10 mg Tab, Justechol 10 mg Tab and Crestolip 10 mg Tab are purchased from the local Egyptian

market. Each tablet is claimed to contain 10.4 mg of Rosuvastatin Calcium.



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Mobile phase preparation: Buffer: Acetonitrile (50:50)

Sodium dihydrogen buffer was prepared by dissolving 6.85 gm of sodium dihydrogen phosphate

monohydrate in 700 mL distilled water and sonicated to dissolve, adjust pH to 4.5 by orthophosphoric acid

solution or triethylamine. Make up to 1000 mL with distilled water, filter and degass mixtures of buffer and

acetonitrile (50:50) through 0.45μ membrane filter under vacuum pump.

Diluent:

Methanol HPLC-grade

Apparatus

HPLC system (Shimadzu LC SPD 20 A) with a detector (dual wavelength), equipped with a binary pump, Autosampler, oven CTO-20A/20AC with temperature range (10-85◦C), LC Solution software.

Mettler pH Meter.

Shimadzu analytical balance.

Ultra-sonic bath.

HPLC Chromatographic Conditions

Chromatographic separation is performed on column Agilent Eclipse XDB- C8 (250 X 4.6 mm i.d, 5 µm particle

size) .Using a mobile phase mixture of sodium dihydrogenphosphate buffer and acetonitrile in the ratio of

50:50 % v/v at ambient temperature, flow rate of 1.2 mL/min, UV detection is performed at 245 nm, injection volume is 10 μL and run time is 5.0 min.

Preparation of standard and samples solution

Stock solutions of Rosuvastatin Calcium (1000 μg /mL)

100mg of ROS-Ca of the working standard are weighed accurately, transferred into 100 mL volumetric flask,

add 70 mL of diluent and sonicate to dissolve. Complete the volume to the mark with the same diluent and

mix well.

Working standard solutions of Rosuvastatin Calcium (50 μg /mL)

Transfer 5 mL from the stock solution of ROS-Ca into 100 mL volumetric flask, add 70 mL of the diluent and sonicate to dissolve, complete to the mark with the same diluent and mix well. The obtained chromatogram is

shown in Figure 2.

Figure 2: HPLC chromatogram of standard solution of (50μg/mL) of Rosuvastatin Calcium.



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Application to pharmaceutical formulations

Weigh not less than 10 tablets from products mentioned above and determine the average weight of one

tablet. Grind to fine powder. Transfer an accurately weighed weight from powdered tablets equivalent to the

average weight of one tablet into 200-mL volumetric flask. Add about 100 mL diluent, sonicate till dissolve

and complete to volume with the same diluent and mix well. Filter through 0.45 μm syringe filter and inject into the chromatographic system. The obtained chromatogram is shown in (Figure 3). Also, the standard

addition technique has been carried out to assess the validity of the method by spiking the pharmaceutical

formulation with known amount of standard solution of ROS-Ca. The recovery of the added standards is then

calculated after applying the proposed method.

Construction of calibration curves:

Different concentrations of ROS-Ca equivalent to (5–100) μg /mL, are separately withdrawn from their

respective stock standards into separate series of 100 mL volumetric flasks, and the volumes are made up to

the mark with the diluent. Duplicate 10 µL injections are made for each concentration maintaining the flow

rate at 1.2 mL/min and the effluent is UV- scanned at 245 nm. The chromatographic separation is performed

following the procedure under chromatographic conditions. The chromatograms are recorded, peak areas of

ROS-Ca are determined and the calibration curves relating the obtained integrated peak areas to the

corresponding concentrations are constructed and the regression equations are performed

. RESULTS AND DISCUSSION

The goal of this study is to develop HPLC assay for the analysis of Ros.Ca drug in its pure form and in

pharmaceutical formulation. Although, the literature is full of a number of HPLC methods for the

determination of rosuvastatin calcium [43-50] due to the high accuracy and precision obtained by HPLC

technique, the present method is devoted, also, for the same goal with aim of achieving better results under

much simpler conditions. Chromatograms are obtained with Rt value of 3.684 min for ROS-Ca with

correlation coefficients (r) =0.9995, limit of detection 1.50 µg mL-1 and limit of quantitation is 4.56 µg mL-1 for

ROS Ca. No occurrence of interfering peaks.

Methods development and optimization

Different developing systems of different compositions and ratios are tried including: methanol: water

(50:50, v/v), acetonitrile: water (50:50, v/v), but no peak was observed for ROS-Ca. Different flow rates are tried (0.7, 1.0, 1.2 and 1.5 mL/min), scanning wavelengths (200 -400 nm) are also tried. Preliminary studies

involved trying C18, C8 reversed-phase columns. The best developing system proved to be sodium dihydrogen phosphate buffer pH (4.5): ACN (50:50, v/v) at flow rate of 1.2mL/min and at wavelength of 245.0

nm using column Agilent Eclipse XDB- C8 (250 mm X 4.6 mm i.d., 5μm). This selected developing system

allows good separation and sharp peak with good Rt values without tailing of the separated bands and good

theoretical plates.

Validation of the Analytical Method

The method is validated, in accordance with ICH guidelines (ICH Q2R1), for system suitability, precision,

accuracy, linearity, specificity, ruggedness, robustness, LOD and LOQ [54].

Linearity and range

The linearity of the proposed methods is obtained in the concentration range (5.0 -100.0 μg/mL) for

Rosuvastatin Calcium. Calibration curves are composed by plotting peak areas against the corresponding

concentrations. The obtained coefficients of regression are 0.9995 for ROS-Ca. Linearity results are shown in

Table 1.

Repeatability

Repeatability of the method is evaluated by calculating the RSD of the peak areas of six replicate injections for

the standard concentration (50.0 μg/mL) of ROS-Ca. Results are examined as % RSD values of the



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concentrations of the determined drug. Low values of % RSD (less than 2) indicate high precision of the

method as shown in Table 1.

Table 1: Regression and validation parameters of the proposed HPLC method for determination of

ROS-Ca

ROS-Ca Parameter

Linear

5-100 range (µg/mL) 32348.6829 Slope 8420.0893 Intercept

0.9995 Correlation coefficient 1.50 LOD a (µg/mL) 4.56 LOQ a (µg/mL)

0.013 Repeatability b

aLimit of detection (3.3× σ /Slope) and limit of quantitation (10× σ /Slope). b Repeatability for n≥5, RSD ≤2.

Table 2: Data of Accuracy for ROS-Ca.

ROS-Ca. Standard (μg/mL) ROS-Ca

μg/mL (Injected) μg/mL (found) Recovery%

25 25 25.37 101.48%

25 25.33 101.33%

25 25.30 101.20%

50 50 50.03 100.06%

50 50.04 100.09%

50 50.07 100.13%

80 80 79.39 99.24%

80 78.78 98.47%

80 78.64 98.30%

Accuracy (Mean) 100.04

Table 3: Determination of ROS-Ca in pharmaceutical formulation by the proposed HPLC method and

application of standard addition

technique

Recovery % Added(µg/mL) Pharmaceutical formulation

ROS-Ca ROS-Ca

99.13 10 Crestolip 10 mg Tab

ROS Ca, 10.4 mg(claimed)

Mean ± RSD

100.31 20 98.53 30

99.32±0.91



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Table 4: Assay result for the determination of Rosuvastatin Calcium in pharmaceutical formulation by

the proposed HPLC method.

limit % Recovery % Conc.(µg/mL) Pharmaceutical formulation

ROS-Ca ROS-Ca ROS-Ca

(90 -110) 104.75% 50 Cholerose 10 mg Tab


Mean ± RSD

104.72% 104.52% 104.81% 104.87% 104.92%

104.76±0.13





(90 -110) 105.30% 50 Crestore 10 mg Tab


Mean ± RSD

106.69% 106.39% 107.76% 107.26% 103.43%

106.14±1.47





(90 -110) 105.48% 50 Estero-map 10 mg Tab


Mean ± RSD

105.29% 105.56% 105.61% 105.55% 105.86%

105.55±0.17





(90 -110) 100.52% 50 Advochol 10 mg Tab


Mean ± RSD

100.58% 100.32% 100.48% 100.41% 100.55%

100.47±0.09



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(90 -110) 104.27% 50 Justechol 10 mg Tab


Mean ± RSD

104.31% 104.29% 104.75% 104.30% 104.31%

104.37±0.18

Detection and Quantitation limits

These approaches are based on the Standard Deviation of the Response and the Slope. A specific calibration curve should be studied using samples containing an analyte in the range of LOD and LOQ. The residual

standard deviation of a regression line or the standard deviation of y-intercepts of regression lines may be

used as the standard deviation. LOD= 3.3 × σ /slope and LOQ =10 × σ /slope, where σ = the standard

deviation of the response Table 1.

Accuracy and recovery

Accuracy of the proposed method is calculated as the percentage recoveries of pure samples of the studied

drugs. Accuracy is assessed using three different concentrations (25, 50 & 80 μg/mL) for ROS-Ca within the

linearity range (i.e. three concentrations and three replicates). Concentrations are calculated from the

corresponding regression equations. The mean % recoveries for ROS-Ca are between 98.0 % to 102 %. These data are shown in Table 2. Accuracy is further assessed by applying the standard addition technique to

Crestolip® 10 mg Tab, where good recoveries are obtained revealing that there is no interference from

excipients, Table 3.

Formulation assay

The validated method is applied to the determination of ROS-Ca in commercially available pharmaceutical

preparations available in the local Egyptian market. The results of the assay indicate that the method is

selective for the analysis of all mentioned products without interference from the excipients. The results are

displayed in Tables 4 - 9.

Intermediate precision (ruggedness)

Intermediate precision expresses within-laboratories variations: different days, different analysts, different

equipment's, etc. Good results are obtained and presented in Table10.

Robustness

The robustness of the proposed method is evaluated in the development phase where the effects of different

factors on the method are studied to obtain the optimum parameters for complete separation. Robustness of

the method is studied by deliberately varying parameters like flow rate (±0.1 mL/min) and studying the

effect of changing mobile phase pH by (± 0.2), acetonitrile composition (±5%) and column temperature

changed (±5°c). The low values of the % RSD, as given in Table11, indicate the robustness of the proposed

method.

System suitability

System suitability testing is an integral part of many analytical procedures. The tests are based on the concept

that the equipment, electronics, analytical operations and samples to be analyzed constitute an integral

system that can be evaluated as such. System suitability is checked by calculating tailing factor (T), column



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efficiency (N), resolution (Rs) factors. All calculated parameters are within the acceptable limits indicating

good selectivity of the method and ensuring system performance, Table 12.

Stability of the analytical solution

To demonstrate the stability of standard solution during analysis, solution is analyzed over a period of 24 h at room temperature and refrigerator. The results showed that for all the solutions, the retention times and

peak areas of ROS-Ca remained almost unchanged (RSD<2.0%) indicating that no significant degradation

occurred within this period, i.e. solutions are stable for at least 24 h, which is sufficient to complete the whole

analytical process. The results are displayed in Table 13.

Specificity

Placebo interference:

Method specificity is determined for samples of studied compounds and placebo matrix containing all

excipients present in the finished product. No interferences are detected at the retention time of ROS-Ca. Also,

the inactive ingredients content of the pharmaceutical preparations do not interfere with HPLC procedure.

Forced degradation:

Forced degradation of the active pharmaceutical ingredient (API) was carried out according to ICH guidelines

(ICH, Q2B) in acid, base, oxidation, photo and heat.





(90 -110) 105.53% 50 Crestolip 10 mg Tab


Mean ± RSD

105.47% 105.59% 105.80% 105.53% 105.53%

105.57±0.11

Table 10: Ruggedness of the method

Table 11: Robustness of the method

Parameter(%RSD) ROS-Ca

Flow rate change (±0.1 mL/min) 1.253

pH change of mobile phase (±0.2) 1.425

Wave length change (±0.2nm) 0.889

Column temperature change(±5ₒC) 0.643

Parameter(%RSD) ROS-Ca

Intraday 0.159

Interday 0.989

Analyst to Analyst 0.168

Column to Column 0.353



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Table 12: System suitability testing parameters of the developed method

Item Obtained Value Reference values

ROS-Ca

Tailing factor 1.110 T ≤ 2

Resolution - Rs>2

Selectivity 3.5 k’ > 2

Injection precision 0.178 RSD ≤1%

Retention time (Rt) 0.122 RSD ≤1%

Number of theoretical plates(N) 5530.772 N > 2000

Table 13: Result of stability of analytical solution

Table 14: Results of analysis for forced degradation study samples using the proposed method,

indicating percentage degradation of

ROS-Ca

Parameter Rosuvastatin Calcium

Effect Observed tR Peak Area Degradation %

Test Without Effect(control) 3.684 1668239 -

Oxidation Effect 3.705 220023 86.81

Alkali Effect 3.198 1550541 7.05

Acid Effect 3.857 1494943 10.38

Light Effect (Sun light) 3.687 1621340 2.81

Heat Effect 3.682 1656890 0.68

Placebo No peak observed No area observed -

Photo degradation:

The powder of working standard ROS-Ca is kept under sunlight for 48 hours. From this powder, accurately

weigh 10.0 mg and transfer to 200-mL volumetric flask. Add 100 mL of diluent and sonicate to dissolve. Make

up to the mark with water and mix well. Filter through 0.45 μm membrane filter, reject the first portion then

analyze by HPLC. No interference is found at the retention time of ROS-Ca and no degradation products

appeared after light degradation.

Heat degradation:

Keep the powder sample of the working standard ROS-Ca in dry oven at 80ºC for 6 hours. Similarly, accurately weigh 10.0 mg and transfer to 200-mL volumetric flask. Add 100 mL of diluent and sonicate to

dissolve. Make up to the mark with water and mix well. Filter through 0.45 μm membrane filter, reject the

first portion then analyze by HPLC. No interference is found at the retention time of ROS-Ca and no

degradation products appeared after heat degradation.

Condition ROS-Ca

Fridge (2-8°C) 100.69%

Room temperature (25°C) 100.67%



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Acid degradation:

Accurately weigh 10.0 mg of the working standard ROS-Ca powder and transfer into 200-mL conical flask.

Add 100 mL of diluent and sonicate to dissolve, add 10 mL of 0.1 N HCl then keep the acidified solutions in

room temperature for one day. Then complete to the mark with diluent and mix well. Filter and analyze by

HPLC. No interference is found at the retention time of ROS-Ca and no degradation products appeared after

acid degradation.



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Figure 3.Typical HPLC chromatogram of sample solution (50μg/mL) of each (a)Cholerose 10 mg Tab,

(b)Crestore 10 mg Tab, (c)Estero-map 10 mg Tab, (d) Advochol 10 mg Tab, (e) Justechol 10 mg Tab

and (f) Crestolip 10 mg Tab.



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Figure 4: HPLC chromatograms of 50 µg/ml solution of (a) Rosuvastatin Calcium after exposure to (b)

heat degradation, (c) photo degradation, (d) acid degradation, (e) base degradation and (f) oxidative

degradation.

Base degradation:

Similarly, weigh 10.0 mg of the working standard ROS-Ca powder and transfer it into 200-mL conical flask.

Add 100 mL of diluent and sonicate to dissolve, add 10 mL of 0.1 N NaOH then keep the alkaline solutions in

room temperature for one day. Then complete to the mark with diluent and mix well. Filter and analyze by

HPLC. No interference is found at the retention time of ROS-Ca but its peak area is affected after base

degradation. The degradation percent is calculated and displayed in (Table 14).

H2O2 degradation:

Finally, weigh 10.0 mg of the working standard ROS-Ca powder and transfer into 200-mL conical flask. Add

100 mL of diluent and sonicate to dissolve, add 15 mL of 3.0 % H2O2 then keep at room temperature for one

day. Then complete to the mark with the diluent and mix well. Filter and analyze by HPLC. No interference is found at the retention time of ROS-Ca but some degradation products appeared after the H2O2 treatment. The



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degradation percent is calculated and displayed in (Table 14). The corresponding chromatogram obtained is

shown in (Figure 4).

CONCLUSION

The proposed RP-HPLC method for determination of Rosuvastatin Calcium in pure and tablets dosage form is,

precise, specific, accurate and less time consuming for analysis, low cost and rapid. The results of forced

degradation undertaken according to the International Conference on Harmonization (ICH) guidelines reveal

that the method is selective. Based on the above results, the analytical method is valid, fit for use and can be

used for regular routine analysis and stability study.

Acknowledgement

The authors are thankful to chemist Mahmoud A Mohamed, QQC Supervisor at EPCI part of HIKMA group,

Beni-Suef, Egypt for his valuable help and providing training and guidance for the second author throughout

the performance of the present work.

REFERENCES

1) British Pharmacopoeia, Stationary Office, Medicines and Healthcare Products Regulatory Agency, London, Vol. II, 2017.

2) European Pharmacopeia 9th edition 2017.

3) https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM20

5893.

4) Ramadan A, Mandil H, Alshelhawi N. Spectrophotometric Determination of Rosuvastatin Calcium in Pure

Form and Pharmaceutical Formulations by The Oxidation Using Iodine and Formation Triiodide

Complex in Acetonitrile. Int J Pharm Pharm Sci. 2014; 6(5):579-585.

5) Gupta A, Mishra P, Shah K. Simple UV Spectrophotometric Determination of Rosuvastatin Calcium in Pure

Form and in Pharmaceutical Formulations. E-Journal of Chemistry. 2009; 6(1):89-92.

6) Lahare RY,Phuge AN,Gite AL,Jadhav AK. A Review on Ultraviolet Spectrophotometric Determination of RosuvastatinCalcium in Marketed Formulation. Int J Pure App Bio sci. 2014; 2 (6):169-174.

7) Uyar B, Celebier M, Altinoz S. Spectrophotometric determination of rosuvastatin calcium in tablets.

Pharmazie. 2007; 62: 411–413.

8) Pandya CB, Channabasavaraj KP, Shridhara HS. Simultaneous Estimation of Rosuvastatin Calcium and

Ezetimibe in Bulk and Tablet Dosage Form by Simultaneous Equation Method. IJCRGG. 2010; 2(4):2140-

2144.

9) Pandya N, Mashru RC. Simultaneous Estimation of Rosuvastatin Calcium and Clopidogrel Bisulfate in

Combined Pharmaceutical Formulation. IJDFR. 2012; 3(5):40-53.

10) Anuradha GK, Vishal SD. Simultaneous Estimation of Rosuvastatin And Ezetimibe by Ratio Spectra Derivative Spectrophotometry Method in Their Fixed Dosage Forms. IJPRIF. 2010; 2(1):404-410.

11) Savita NM, Promod SH, Chandrashekhar BL. Quantitative Determination of Rosuvastatin Calcium and

Niacin Individually and Combined Tablet Dosage Form by Using UV-VIS Spectrophotometer.

International Journal of Pharma Research & Review. 2015; 4(6):37-43.

12) Solanki C, Patel N, Patel V, Patel D, Vaishy R. Development and Validation of First Order Derivative

Spectrophotometric Method for Simultaneous Estimation of Rosuvastatin Calcium and Aspirin in Capsule

Dosage Form. Der Pharmacia Lettre 2012; 4(3):947-953 .

13) Anuradha GK,Vishal SD. Simultaneous UV spectrophotometric Estimation Of Rosuvastatin And Ezetimibe

In Their Combined Dosage Forms. International Journal of Pharmacy and Pharmaceutical Sciences.

2010; 2(1):131-138.

14) Mandwal PS, Patel PR, Agarwal KM, Surana SJ. Q-Absorbance and Multicomponent UV -

Spectrophotometric Methods for Simultaneous Estimation of Rosuvastatin calcium and

Fenofibrate in Pharmaceutical Formulation.Der Pharmacia Lettre 2012; 4(4):1054-1059.



25

15) Patel B, Jadav A, Solanki H, Parmar S, Parmar V, Captain A. Development and Validation of Derivative

Spectroscopic Method for the Simultaneous Estimation of Rosuvastatin Calcium and Fenofibrate in

Tablet. International Journal of Pharma Research & Review. 2013; 2(7):1-6.

16) Tank PH, Vadalia KR, Dedania ZR. Development and Validation of Hptlc Method for Simultaneous

Estimation of Rosuvastatin Calcium and Aspirin in Capsule Dosage Form. IJPSR. 2102; 3(10):3867-3870. 17) Su¨slu¨ I, Celebier M, Altıno¨z S. Determination of Rosuvastatin in Pharmaceutical Formulations by

Capillary Zone Electrophoresis. Chromatographia. 2007; 66(1):65-72.

18) Zhang D, Zhang J, Liu X, Wei C, Zhang R, Song H, Yao H. Validated LC-MS/MS Method for the

Determination of Rosuvastatin in Human Plasma: Application to a Bioequivalence Study in Chinese

Volunteers. Pharmacology & Pharmacy. 2011; 2: 341-346.

19) Ishaq BM, Prakash KV, Kumar CH, Rani GU, Mohan GK. Development and validation of LC-MS method for

the determination of Rosuvastatin Hydrochloride in human plasma. J. Chem. Pharm. Res. 2010;

2(6):324-333.

20) Hull CK, Penman AD, Smith CK, Martin PD. Quantification of rosuvastatin in human plasma by automated

solid-phase extraction using tandem mass spectrometric detection. Journal of Chromatography B. 2002;

772(2): 219–228.

21) Gao J, Zhong D, Duan X, Chen X. Liquid chromatography/negative ion electrospray tandem mass

spectrometry method for the quantification of rosuvastatin in human plasma: Application to a

pharmacokinetic study. Journal of Chromatography B 2007; 856(1–2): 35–40. 22) Xu DH, Ruan ZR, Zhou Q, Yuan H , Jiang B. Quantitative determination of rosuvastatin in human plasma by

liquid chromatography with electrospray ionization tandem mass spectrometry. Rapid Commu-nications

in Mass Spectrometry. 2006; 20(16): 2369-2375, doi:10.1002/rcm.2542 .

23) Siddartha B, Babu S. Estimation and Validation for Determination of Rosuvastatin In Human Plasma by

Lc/Ms/Ms Method. JGTPS. 2014; 5(3):1979–1988.

24) Zaid A, Al Ramahi R, Cortesi R, Mousa A, Jaradat N, Ghaza N, Bustami R. Investigation of the

Bioequivalence of Rosuvastatin 20 mg Tablets after a Single Oral Administration in Mediterranean Arabs

Using a Validated LC-MS/MS Method. Sci. Pharm. 2016; 84: 536–546; doi:10.3390/scipharm84030536.

25) Sheth A, Patel KN, Ramlingam B, Shah N. Simultaneous Estimation of Rosuvastatin Calcium and

Clopidogrel Bisulphate From Bulk and Commercial Products Using a Validated Reverse Phase High Performance Liquid Chromatographic Technique. IRJP. 2012; 3(11):154-157.

26) Bhati LK, Kumar MV. Bilayer Tablet of Rosuvastatin Calcium and Fenofibrate: An Assessment Prior To

Formulation Design. Ejpmr. 2016; 3(6): 391-395.

27) Turabi ZM, Khatatbeh OA. Stability-Indicating RP-HPLC Method Development and Validation for the

Determination of Rosuvastatin (Calcium) In Pharmaceutical Dosage Form. Int. J. Pharm. Sci. Drug Res.

2014; 6(2): 154-159 .

28) Substances in solid oral dosage form using the developed and validated, stability indicating, RP-UPLC

method,Chapter-4, "Determination of Related Substance in Rosuvastatin Tablets by RP-UPLC

Method",117-146. 29) Thriveni J, Rambabu R, Rao JV, Vidyadhara S. Development and Validation of Rp-Hplc Method For

Simultaneous Estimation of Rosuvastatin Calcium and Fenofibrate In Bulk and Pharmaceutical Dosage

Forms. IJRPC. 2013; 3(2):208-212.

30) Petkovska R, Cornett C, Dimitrovska A. Development and Validation of Rapid Resolution RP-HPLC Method

for Simultaneous Determination of Atorvastatin and Related Compounds by Use of Chemometrics.

JournalAnalytical Letters 2008; 41( 6):992-1009.

31) Varma PD, Rao AL, Dinda SC. Development and Validation of Stability Indicating Rp-Hplc Method for

Simultaneous Estimation of Rosuvastatin And Ezetimibe in Combined Tablet Dosage Form. RASAYAN J

Chem. 2012; 5(3):269-279.

32) Karunakaran A, Subhash V, Chinthala R, Muthuvijayan J. Simultaneous Estimation of Rosuvastatin

Calcium and Fenofibrate in Bulk and in Tablet Dosage Form by UV-Spectrophotometry and RP-HPLC. S J

Pharm Sci. 2011; 4(1): 58-63.



26

33) Pandya CB, Channabasavaraj KP, Shridhara HS. Simultaneous Estimation of RosuvastatinCalcium and

Ezetimibe in Bulk and Tablet Dosage Form by Simultaneous EquationMethod. Int J ChemTech Res.

2010; 2(4):2140-2144.

34) Tajane D, Raurale AM, Bharande PD, Mali AN, Gadkari AV, Bhosale VR. Development and validation of a

RP-HPLC-PDA method for simultaneous determination of Rosuvastatin calcium and Amlodipine besylate in pharmaceutical dosage form. J Chem Pharm Res. 2012; 4(5):2789-2794.

35) Swathi Sd, Hemant KT, Vara Prasada RK, Srinivasa RY. Validated Rp-Hplc Method for Simultaneous

Determination of Rosuvastatin Calcium and Ezetimibe in Pharmaceutical Dosage Form. Int J Pharm

Pharm Sci. 2015; 7(4): 209-213.

36) Chakraborty AK, Mishra SR, Sahoo HB. Formulation of Dosage Form of Rosuvastatin Calcium And

Development of Validated Rp-Hplc Method for Its Estimation. International Journal of Analytical and

Bioanalytical Chemistry. 2011; 1(3): 89-101.

37) Sultana N, Arayne MS, Ali SN. An Ultra-Sensitive LC Method for Simultaneous Determination of

Rosuvastatin, Alprazolam and Diclofenac Sodium in API, Pharmaceutical Formulations and Human Serum

by Programming the Detector. J Anal Bioanal Techniques 2012; 3(7):1-6.

38) Sultana N, Arayne MS, Shah SN, Shafi N, Naveed S. Simultaneous Determination of Prazosin, Atorvastatin,

Rosuvastatin and Simvastatin in API, Dosage Formulations and Human Serum by RP-HPLC. Jnl Chinese

Chemical Soc. 2010; 57(6):1286.

39) Solanki C, Patel N. Development and Validation of Rp-Hplc Method for Simultaneous Estimation of Rosuvastatin Calcium and Aspirin in Capsule Dosage Form . Int J Pharm Bio Sci. 2012; 3(3): 577 – 585.

40) Sultana N, Arayne MS, Iftikhar B. Simultaneous Determination of Atenolol, Rosuvastatin, Spironolactone,

Glibenclamide and aproxen Sodium in Pharmaceutical Formulations and Human Plasma by RP-HPLC. Jnl

Chinese Chemical Soc. 2008; 55(5): 1022–1029.

41) Arayne MS, Sultana N,Tabassum A, Ali SN,Naveed S. Simultaneous LC determination of rosuvastatin,

lisinopril, captopril, and enalapril in API, pharmaceutical dosage formulations, and human serum. Med

Chem Res. 2012; 21:4542. doi:10.1007/s00044- 012-9997-x.

42) Raj HA, Rajput SJ, Dave JB, Patel CN. Development and Validation of Two Chromatographic Stability-

Indicating Methods for Determination of Rosuvastatin In Pure Form and Pharmaceutical Preparation. Int

J ChemTech Res. 2009; 1(3):677-89. 43) Pandya CB, Channabasavaraj KP, Chudasama JD, Mani TT. Development and Validation of Rp-Hplc

Method for Determination of Rosuvastatin Calcium in Bulk and Pharmaceutical Dosage Form. 2010;

5(1)82-86.

44) Kaila HO, et al. A new improved RP-HPLC method for assay of rosuvastatin calcium in tablets. Indian

journal of pharmaceutical scienc. 2010; 72(5): 592.

45) Donthula S, Kumar MK, Teja GS, Kumar YM, Krishna JY, Ramesh D. A new validated RP-HPLC method

for determination of Rosuvastatin calcium in bulk andpharmaceutical dosage form. Der Pharmacia

Lettre. 2011; 3(3): 350-356.

46) Safwan A , Omar A. Validated high-performance liquid chromatographic method for the estimation of rosuvastatin calcium in bulk and pharmaceutical formulations. International journal of biomedical

science. 2011; 7(4): 283.

47) 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. Scientia

Pharmaceutica. 2012;80(2):393-406. doi:10.3797/scipharm.1201-09.

48) Mostafa Nadia M, et al. Selective Chromatographic Methods For The Determination Of Rosuvastatin

Calcium In The Presence Of Its Acid Degradation Products. Journal of Liquid Chromatography & Related

Technologies. 2014; 37(15): 2182-2196.

49) Smitha G, Sharath S, Reddy C, Sameer Kumar D, Shiva Kumar J, Jukanti Raju. Rosuvastatin calcium

Quantification in Rat Serum with the aid of RP-HPLC: Method Development and Validation. IOSR Journal

of Pharmacy and Biological Sciences. 2015;10(5): 23-28., DOI: 10.9790/3008-10522328

50) Kumar HT, Sri SD, Rao VPK and Rao SY. Validated RP-HPLC Method for Determination of Rosuvastatin

Calcium in Bulk and Pharmaceutical Formulation. Int J Pharm Sci Res. 2015; 6(7): 2913-17.doi:

10.13040/IJPSR.0975-8232. 6(7).2913-17.



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51) Altınöz S, Uyar B. Electrochemical behaviour and voltammetric determination of rosuvastatin calcium in

pharmaceutical preparations using a square-wave voltammetric method. Ana Methods. 2013; 5: 5709-

5716.

52) Ramadan A, Mandil H, Ghazal N. Electrochemical Behavior and Differential Pulse Polarographic

Determination of Rosuvastatin In Pure Form and In Pharmaceutical Preparations Using Dropping Mercury Electrode . Int J Pharm Pharm Sci. 2014; 6(3): 128-133.

53) Baldut M, Bonafede SL, Petrone L, Simionato LD, Segall AI. Development and Validation of a

ComplexometricTitration Method for the Determination of Rosuvastatin Calcium in Raw Material. AIR.

2015; 5(5): 1-8.

54) ICH, Q2 (R1) Validation of Analytical Procedures: Text and Methodology. ICH Harmonized Tripartite

Guideline (2005).

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