Development and Validation of RP-HPLC Method for Estimation of Lurasidone and its impurities Lurasidone 1 and Lurasidone 8

 

Maulikkumar D. Vaja1*, Ruchita R. Patel2, Bhoomi D. Patel3, Ankit B. Chaudhary4

1Associate Professor, Saraswati Institute of Pharmaceutical Sciences,

Dhanap, Gandhinagar, Gujarat, India – 382355.

2Student, Saraswati Institute of Pharmaceutical Sciences, Dhanap, Gandhinagar, Gujarat, India – 382355.

3Associate Professor, Saraswati Institute of Pharmaceutical Sciences,

Dhanap, Gandhinagar, Gujarat, India – 382355.

4Principal and Professor, Saraswati Institute of Pharmaceutical Sciences,

Dhanap, Gandhinagar, Gujarat, India – 382355.

*Corresponding Author E-mail: maulikvaja@yahoo.in

 

ABSTRACT:

Objective: The aim of the present work is the development of new, sensitive, specific, and accurate high-performance liquid chromatographic method for the Estimation of Lurasidone and its Impurities Lurasidone 1 and Lurasidone 8. Methods: The chromatographic separation of drug and its impurities was achieved using Inertsil ODS C18 column (150mm x 4.6mm, 5μm) with mobile phase consisted of mobile phase-A 0.05M Potassium Dihydrogen Phosphate buffer (pH- 4.0, adjusted with 1% Orthophosphoric acid) and mobile phase-B Acetonitrile in the ratio  of 60:40 % v/v at a flow rate of 1.0 ml/min with ultraviolet detection at 230 nm. Results: Lurasidone and its Impurities Lurasidone 1 and Lurasidone 8 were successfully eluted at the retention time of 6.022, 5.024 and 10.456 min respectively, with good resolution. The described method was linear over a concentration range of 160-1200 μg/ml for Lurasidone, 1.6-12 μg/ml for Lurasidone 1 and Lurasidone 8. The % recoveries of Lurasidone was found to be 100.565% - 101.061%. The method was validated according to the international conference on harmonization guidelines. The validation results showed good precision, accuracy, linearity, specificity, sensitivity, and robustness. Conclusion: Successful separation and Estimation of Lurasidone and its Impurities Lurasidone 1 and Lurasidone 8 were achieved by the proposed method. The developed method can be applied for the routine analysis of Lurasidone and its impurities in pharmaceutical formulations.

 

KEYWORDS: Lurasidone, Lurasidone 1, Lurasidone 8, Reverse-phase high-performance liquid chromatography method, Impurity, Method validation.

 

 

INTRODUCTION:

Lurasidone is chemically designated as  (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl} hexahydro-4,7-methano-2H-isoindole-1,3-dione and has the molecular weight 492.78 g/mol (figure-1).1 Lurasidone is an atypical antipsychotic that is a D2 and 5-HT2A (mixed serotonin and dopamine activity) to improve cognition.

 

It is thought that antagonism of serotonin receptors can improve negative symptoms of psychoses and reduce the extrapyramidal side effects that are often associated with typical antipsychotics Various Analytical Methods have been reported for the Estimation of Lurasidone as alone. They included RP-HPLC, UV Spectrophotometric methods.1

 

Lurasidone 1 is chemically designated as (3aR,7aR)-4'-(benzo[d]isothiazol-3yl)octahydrospiro[isoindole-2,1'-piperazin]-2-ium and has the molecular weight 328.5 g/mol. (figure-2) There is not individual methods have been reported for the estimation of Lurasidone 1 as alone. Lurasidone 8 is chemically designated as and has the molecular weight 509.70 g/mol1  (figure-3). There is not individual methods have been reported for the estimation of Lurasidone 1 and Lurasidone 8 as alone. The literature survey reveals that there are various reported analytical method are available for estimation of Lurasidone alone and with other combination and other Impurities 2-31

 

The literature survey does not reveal that any method is reported for Estimation of Lurasidone and its impurities Lurasidone-1 and Lurasidone-8.

 

Fig.1 Chemical structure of Lurasidone

 

Fig.2 Chemical structure of Lurasidone Impurity 1

 

Fig.3 Chemical structure of Lurasidone Impurity 8

 

MATERIALS AND METHOD:32

Reagents and Chemicals:

Lurasidone, Lurasidone 1 and Lurasidone 8 were obtained as gift samples from Rivan Pharmaceutical Ltd, Ahmedabad. The branded tablet formulation Luramax Tablet (Lurasidone HCl 40mg) was purchased from the local market. HPLC grade Acetonitrile, Water and Ortho-phosphoric acid, and Potassium Dihydrogen Phosphate of analytical grade were obtained from Finar Chemicals Ltd.

 

Instruments and Chromatographic Conditions:

The analysis was performed on Young lin (YL 9100) software. The separation was achieved on Inertsil ODS C18 column (150 x 4.6mm, 5µm) column. The column was maintained at room temperature and the eluent was monitored at 230 nm using DAD detector. The mixture of 0.05M Phosphate Buffer pH 4.0 and Acetonitrile in proportion of 60:40%v/v at a flow rate of 1.0 ml/min was used as mobile phase. The injection volume is 20μl.

Preparation of Mobile Phase:

Preparation of Diluted Ortho phosphoric acid:

A 1 ml of Ortho phosphoric acid was transferred in to 100 ml volumetric flask and volume was made up to the mark with HPLC grade water and mixed thoroughly.

 

Preparation of 0.05 M phosphate buffer (pH 4.0):

A 3.4 gm of KH2PO4 was weigh accurately and transfer into 500ml of Volumetric flask. 250ml of HPLC grade water was added and shaken to dissolved. The solution was diluted up to the mark and then mixed. Record the Initial pH of this solution is 6.7 and pH 4.0 was adjusted with diluted ortho phosphoric acid.

 

Preparation of mobile phase (0.05M phosphate buffer (KH2PO4): Acetonitrile, 60:40 % v/v):

Accurately measured 400 mL of Acetonitrile and 600 mL of above prepared 0.05M phosphate buffer (pH 4.0) were mix thoroughly and degassed by sonication.

 

Preparation of Diluents:

Use Methanol as Diluent.

 

Preparation of stock solutions:

Standard stock solution of Lurasidone (8000 μg/ml):

A 800 mg of Lurasidone weighed accurately and transferred in to 100 ml volumetric flask and dissolved with few ml of methanol, then volume was made up to the mark with methanol and mixed thoroughly.

 

Standard stock solution of Lurasidone Impurity 1 (80 μg/ml):

A 8 mg of Lurasidone Impurity 1 weighed accurately and transferred in to 100 ml volumetric flask and dissolved with few ml of methanol, then volume was made up to the mark with methanol and mixed thoroughly.

 

Standard stock solution of Lurasidone Impurity 8 (80 μg/ml):

A 8 mg of Lurasidone Impurity 8 weighed accurately and transferred in to 100 ml volumetric flask and dissolved with few ml of methanol, then volume was made up to the mark with methanol and mixed thoroughly.

 

Working combine standard solution of Lura, Lura 1 and Lura 8 (800: 8:8 μg/ml):

A 1 ml of standard stock solution of Lurasidone (8000 μg/ml), 1 ml of standard stock solution of Lurasidone Impurity 1 (80 μg/ml) and 1 ml of standard stock solution of Lurasidone Impurity 8 (80 μg/ml) were transferred in to 10 ml volumetric flask, volume was made up to the mark with methanol and mixed thoroughly.

 

Preparation of Sample solution:

An average weight of 20 tablets was determined and tablets were crushed in to powder form. Accurately weighed amount of powder equivalent to 80 mg of Lurasidone was transferred in to 100 ml volumetric flask. About 60 ml of methanol was added and solution was sonicated for 30 min. to ensure complete solubilisation of drugs. Then solution was filtered through whatman filter paper and then volume was made up to the mark with methanol. (800 μg/ml of Lurasidone).

 

RESULT AND DISSCUSION:

Specificity:

Specificity was checked by comparison of chromatogram of diluents, chromatogram of standard Lurasidone (800 μg/ml), Lurasidone Impurity 1(80 μg/ml), and Lurasidone Impurity 8(80 μg/ml) and their Combination, sample of Lurasidone. The method was found to be specific as there was no interference observed in any of the parameters under observation.

 

Linearity and Range:

The linearity was observed for Lurasidone, Lurasidone Impurity 1 and for Lurasidone Impurity 8 over the Concentration range of  160 to 1200 µg/ml, 1.6 to 12 µg/ml and 1.6 to 12 µg/ml, respectively.

 

 

 

Fig. 4: Calibration Curve of Lurasidone at 230 nm Wavelength

 

 

Fig. 5: Calibration Curve of Lurasidone 1 at 230 nm Wavelength

 

Fig. 6: Calibration Curve of Lurasidone 8 at 230 nm Wavelength

 

Table 1: Data for linearity and range

Sr. No

Concentration

(µg/ml)

Average

Area ± SD (n=3)

Concentration

For Imp (µg/ml)

Average

Area ± SD (n=3) (Imp 1)

Average

Area ± SD (n=3) (Imp 8)

1

160

6473.992 ± 52.154

1.6

53.733 ± 0.518

53.733 ± 0.518

2

400

12164.542 ± 55.652

4

127.567 ± 1.249

127.567 ± 1.249

3

600

18132.597 ± 44.415

6

195.385 ± 1.098

195.385 ± 1.098

4

800

24192.461 ± 72.622

8

268.232 ± 2.028

268.232 ± 2.028

5

1000

30049.364 ± 32.306

10

328.443 ± 1.142

328.443 ± 1.142

6

1200

36263.389 ± 80.815

12

402.052 ± 1.682

402.52        ± 1.682

 

Table 2: Precision Study For Lurasidone, Lurasidone 1 and Lurasidone 8

Parameters

Concentration (µg/ml)

%RSD

 

LURA

LURA Imp 1

LURA Imp 8

LURA

LURA Imp 1

LURA Imp 8

Repeatability

800

8

8

1.488.852

1.557

0.385

Intraday

160

1.6

1.6

1.733

0.890

1.077

 

800

8

8

1.649

1.470

1.152

 

1200

12

12

1.343

1.706

1.804

Interday

160

1.6

1.6

1.734

1.171

1.960

 

800

8

8

1.885

0.787

1.513

 

1200

12

12

1.526

1.052

1.437

Table 3: Recovery data for Lurasidone

Sr. No.

Conc.

Level (%)

Sample amount (μg/ml)

Amount Added (μg/ml)

Amount Recovered (μg/ml)

%

Recovery

% Mean

Recovery

S.D

% R.S.D

1

50 %

400

200

201.129

100.565

100.565

0.827

0.822

2

400

200

202.783

101.391

3

400

200

199.476

99.738

4

100 %

400

400

405.566

101.391

101.006

0.416

0.412

5

400

400

404.243

101.061

6

400

400

402.259

100.565

7

150 %

400

600

608.349

101.391

101.061

0.298

0.295

8

400

600

605.869

100.978

9

400

600

604.876

100.813

 

Table 4: Robustness study for Lurasidone, Lurasidone impurity 1 and Lurasidone impurity 8

Parameters

 

Area

Lurasidone

Lurasidone impurity 1

Lurasidone impurity 8

pH

(±0.2)

3.8

24989.263

273.614

238.592

4.0

24152.625

267.694

240.616

4.2

24652.457

272.543

233.337

Mean± SD

24598.115± 420.958

271.284 ±3.155

237.515 ±3.757

%RSD

1.711

1.163

1.582

Flow Rate

(±0.02 ml/min)

0.98ml/min

24725.732

272.543

238.615

1.0ml/min

24162.625

267.694

240.616

1.02ml/min

24974.893

269.183

241.007

 Mean± SD

24621.083± 416.123

269.807± 2.484

240.079± 1.283

%RSD

1.690

0.921

0.534

Mobile Phase Composition Buffer: ACN (± 2mL)

58:42

24620.808

274.225

241.007

60:40

24141.625

267.694

240.616

62:38

24565.932

265.096

236.337

Mean± SD

24442.788± 262.254

269.005±4.704

239.320±2.591

%RSD

1.073

1.749

1.083

 

 

Precision:

The % RSD for repeatability study for Lurasidone, Lurasidone 1 and Lurasidone 8  was found to be 1.488, 1.557 and 0.385 respectively. The Inter-day and Intra-day study also show % RSD value for Lurasidone, Lurasidone 1 and Lurasidone 8 within the acceptable limit.

 

Accuracy:

The accuracy of the method was determined at 50%, 100%, and 150% level by calculating recoveries of Lurasidone by the standard addition method. Known amount of standard solutions of Lurasidone (200, 400, 600 μg/ml) was added to a pre-quantified sample solution of Lurasidone (400μg/ml) for Drug. Accuracy of the method was confirmed by recovery study at three levels (50%, 100% and 150%) of standard addition.

 

Robustness:

The typical variations studied under this parameter were mobile phase  composition and detection wavelength. Overall % RSD was found to be less than 2% for all the variations which indicates that the proposed method is robust. Robustness data are shown in Table-4.

 

LOD and LOQ:

The LOD was found to be 59.899µg/ml for Lurasidone, 0.383µg/ml for Lurasidone Impurity 1 and 0.412µg/ml for Lurasidone Impurity 8, while the LOQ was found to be 181.513µg/ml for Lurasidone, 1.161µg/ml for Lurasidone Impurity 1 and 1.247µg/ml for Lurasidone Impurity 8.

 

 

Application to Tablet Dosage Form:

Applicability of the proposed method was tested by analyzing the commercially available marketed formulation. The percentage of Lurasidone was found to be 98.53 %. Results as % Assay are shown in Table 5.

 

Table 5: Analysis of Formulation of Lurasidone by Proposed Method

Lurasidone

Labelled amount (mg)

Amount found (mg) (n=3)

% Assay (n=3)

 

80 mg

78.806

98.508

78.843

98.554

78.821

98.526

Mean ± SD

78.823±0.019

98.529±0.023

 %RSD

0.024

0.023*6

 

 

 

Table 6: % of Known impurity of Lurasidone impurity 1 and Lurasidone impurity 8 by Proposed Method

% of Known impurity

Impurity

Area of known impurity in standard preparation of impurity

STD impurity Concentration

(µg/ml)

test preparation Concentration (µg/ml)

Area of known impurity present in test preparation

% of Known impurity

Mean±SD

%RSD

Lurasidone Impurity 1

268.232

 

8

800

Not Present

-

-

-

Not Present

-

Not Present

-

Lurasidone Impurity 8

237.549

 

8

800

123.983

0.522

0.526±

0.004

0.750

125.856

0.530

124.956

0.526

 

ACKNOWLEDGEMENT:

The authors are also thankful to Saraswati Institute of Pharmaceutical Sciences for providing necessary equipment, facility & chemicals to complete research work and Sincere thanks to my highly respected and esteemed, Principal Dr Ankit B Chaudhary. I would like to express thanks to my parents without their encouragement love and blessings I would not have reached this level manuscript.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

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Received on 05.06.2021             Modified on 16.11.2021

Accepted on 23.02.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(11):4999-5004.

DOI: 10.52711/0974-360X.2022.00840