New spectrophotometric methods for the estimation of Ziprasidone - An Antipsychotic drug

 

Mukthinuthalapati Mathrusri Annapurna*, Volety Malavika

GITAM School of Pharmacy, GITAM (Deemed to be) University, Visakhapatnam-530045, India.

*Corresponding Author E-mail: mmukthin@gitam.edu

 

ABSTRACT:

Ziprasidone hydrochloride monohydrate is an atypical antipsychotic drug which acts by antagonizing the dopamine type 2 (D2) and serotonin type 2 (5HT2A) receptors. It is used for the treatment of schizophrenia as well as manic and bipolar disorders.  Two new spectrophotometric methods have been developed for the determination of Ziprasidone capsules in acetate buffer (pH 4.0) (λmax 315.00 nm) (Method I) and phosphate buffer (pH 5.0) (λmax 315.40 nm) (Method II) respectively and the methods were validated. Beer-Lambert’s law was obeyed over the concentration range 0.5-30 µg/mL and 1-120 µg/mL in acetate buffer and phosphate buffer respectively. The proposed methods were applied to the Ziprasidone marketed formulations and the methods were found to be simple, precise and accurate.

 

KEYWORDS: Ziprasidone, Spectroscopy, Acetate buffer, Phosphate buffer, Validation.

 

 


INTRODUCTION:

Ziprasidone hydrochloride monohydrate (CAS 138982-67-9) is a second-generation atypical antipsychotic drug (Figure 1). It is a piperazine derivative with antischizophrenic properties1-2. Ziprasidone hydrochloride monohydrate (C21H21ClN4OS.ClH.H2O; Molecular weight: 467.42 g/mol) is chemically 5-[2-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl] ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one hydrochloride monohydrate with pKa 6.68. Ziprasidone was estimated by various analytical techniques such as liquid chromatography, spectrophotometry, spectrofluorimetry etc. Analytical methods such as spectrofluorimetry3, spectrophotometry4-18 were thoroughly discussed in detail and the authors have chosen two different reagents for the spectral study in UV region for the determination of Ziprasidone capsules in the present study and the methods were validated.

 

Figure 1: Chemical structure of Ziprasidone hydrochloride monohydrate

 

MATERIALS AND METHODS:

Ziprasidone hydrochloride monohydrate was obtained as gift sample from Torrent pharmaceuticals (India) and it is available as capsules with label claim: 20,40, 60 and 80 mg with brand names, Geodon (Pfizer); Zipsydon (Sun Pharmaceutical Industries Ltd.), Azona (Torrent pharmaceuticals), Zipris (Sunrise Remedies Pvt. Ltd.); Zipra (Zydus Cadila), Zipral (Lifecare neuro products Ltd.), Zipradep (Emco Biotech) etc.

 

Shimadzu Model No. UV – 1800 double beam spectrophotometer with quartz cells was employed for the study and all the solutions were scanned in UV range (200-400 nm) as the solutions were colorless in acetate buffer (pH 4.0) and phosphate buffer (pH 5.0) which were prepared as per IP 2010.

 

Preparation of buffers and Ziprasidone hydrochloride monohydrate stock solution

Acetate buffer (pH 4.0) solution was prepared by mixing 2.86 mL of glacial acetic acid with 1.0 mL of 50% w/v solution of sodium hydroxide in a 1000 mL volumetric flask and the volume was made up to mark with distilled water and sonicated.

 

Phosphate buffer (pH 5.0) solution was prepared by mixing 6.8 g of potassium dihydrogen phosphate in distilled water in a 1000 mL volumetric flask and pH was adjusted to 5.0 using 10M potassium hydroxide.

Stock solution of Ziprasidone hydrochloride monohydrate was prepared by transferring and dissolving 25 mg of the drug in methanol in a 25 mL volumetric flask (1000 µg/mL) and then a series of dilutions were prepared in acetate buffer (0.5-30 µg/mL) and Phosphate buffer (1-120 µg/mL) as per the requirement.

 

Method validation19

A series of Ziprasidone hydrochloride monohydrate solutions were prepared in acetate buffer (0.5-30 µg/mL) and phosphate buffer (1-120 µg/mL) and scanned (200-400 nm) against their reagent blank. Ziprasidone hydrochloride monohydrate has shown λmax at 315.00 nm and 315.40 nm in acetate buffer and phosphate buffer respectively. A calibration curve was drawn by taking the concentration of the drug on the X-axis and the corresponding absorbance on the Y-axis for both the methods.

 

Intraday precision studies were performed (n=6) at different time intervals on the same day and inter day precision studies were performed (n=3) on three consecutive days (Day 1, Day 2 and Day 3) and the statistical parameters were evaluated and accuracy studies were carried out by standard addition method for both the methods.

 

Assay of Ziprasidone capsules

20 capsules of Ziprasidone hydrochloride monohydrate were procured from the pharmacy store and the drug was extracted using methanol. The contents inside the capsules were weighed and the quantity equivalent to 25 mg Ziprasidone hydrochloride monohydrate was accurately weighed transferred into a 25 mL volumetric flask and dissolved in methanol, sonicated and filtered. The filtrate was diluted as per the requirement and the percentage of purity was calculated from the calibration curve obtained for the proposed methods.

 

RESULTS AND DISCUSSION:

Two new spectrophotometric methods have been developed for the determination of Ziprasidone hydrochloride monohydrate in acetate buffer (pH 4.0) and phosphate buffer (pH 5.0) and validated. A review of the previously published spectral methods for the estimation of Ziprasidone hydrochloride monohydrate are shown in Table 1.


Table 1: Review of Spectral methods

Spectrofluorimetric methods

Reagent

Linearity (μg/ml)

λ (nm)

Reference

Acetate buffer pH 4.5

0.05-0.80

315

398

3

Spectrophotometric methods

Saline buffer pH 7.4

2-10

318

4

1M Methanolic HCl

10-70

315

5

Methanol

2-200

316

6

Methanol, Sodium dihydrogen phosphate buffer pH 7.4, 2% SLS

10-70

318

7

0.1N HCl and Tpooo dye

2-10

490

8

Method-A

1N Folin-ciocalteau, sodium bicarbonate and distilled water

Method -B Potassium ferricyanide and distilled water

5-250

 

10-50

436

 

733

9

Method -A

0.003M ferric chloride solution, 0.01M 1,10-phenanthroline and distilled water

Method -B

0.003M ferric chloride solution, 0.03N 2,2’- bipyridyl and double distilled water

 

250-2000

 

500-2500

 

509

 

521

10

Phthallate buffer pH 4

4-24

415

11

0.1N HCl (solvent)

Method -A

N-bromo succinimide (NBS) and p-N-methyl aminophenol-sulphanilamide (PMAP-SA)

Method -B

5.0M HCl, NBS and Celestine Blue with water

Method -C

0.01 HCl, Tannic acid, pH 3.0 buffer and PMAP solution.

 

 

4-24

 

0.4-2.4

 

8-48

 

 

520

 

540

 

560

 

12

Method –A Picric acid

Method –B Chloroanillic acid

4-20

16-36

400

520

13

Gold (III) chloride solution

5-60

600

14

Common solvents for Method-A and B: FeCl3, o-phosphoric acid

Method -A 2,21 bipyridyl solution

Method -B Bathophenanthroline

 

40-200

4-20

 

510

630

15

N-1-naphthyl ethylene diamine dihydrochloride

2-10

540

16

Method -A

3-methyl 2-benzothiazoline hydrazone, FeCl3

Method -B   Methyl orange

 

8-56

3-15

 

640

420

17

Method -A

Brotton-Marshall’s reagent

Method –B 1,10-phenzanthroline, FeCl3, o-phosphoric acid

 

2-10

4-20

 

540

520

18

Acetate buffer pH 4.0

Phosphate buffer pH 5.0

0.5-30

1-120

315.00

315.40

Present

method


Method validation

The absorption spectra of Ziprasidone hydrochloride monohydrate (Figure 2) have shown λmax at 315.00 nm in acetate buffer and at 315.40 nm in phosphate buffer. Ziprasidone hydrochloride monohydrate obeys Beer-Lambert’s law over the concentration range 0.5-30 µg/mL and 1-120 µg/mL in acetate buffer and phosphate buffer respectively (Table 2).

 

Calibration curves were drawn by taking the concentration on the x-axis and the corresponding absorbance on the y-axis. The linear regression equations were found to be y = 0.0154x + 0.0002 (R˛ = 0.9997) and y = 0.0266x + 0.0162 (R˛ = 0.9998) in acetate buffer pH 4.0 and phosphate buffer pH 5.0 respectively (Figure 3).


 

 

 

Figure 2A: Acetate buffer (λmax 315.00 nm)

Figure 2B: Phosphate buffer (λmax 315.40 nm)

Figure 2: Absorption spectra of Ziprasidone hydrochloride monohydrate

 

 

Figure 3A: Acetate buffer

Figure 3B: Phosphate buffer

Figure 3: Calibration curves of Ziprasidone hydrochloride monohydrate

 


Table 2: Linearity of Ziprasidone hydrochloride monohydrate

Conc.  (µg/mL)

Acetate buffer

Phosphate buffer

Absorbance

at λmax 315.00 nm

Absorbance

at λmax 315.40 nm

0.5

0.006

-

1

0.013

0.029

2

0.030

0.057

5

0.083

0.148

10

0.153

0.282

20

0.310

0.568

30

0.459

-

40

-

1.111

50

-

1.367

80

-

2.137

100

-

2.650

120

-

3.211

The percentage RSD in precision and accuracy was found to be 1.0072 (Intraday) and 1.9226 (Inter-day) in acetate buffer and 1.3036 (Intraday) and 1.3937 (Inter-day) in phosphate buffer which is less than 2.0 indicating that the methods are precise. In the accuracy studies, the percentage RSD was found to be 0.76 - 0.98 in acetate buffer (% Recovery 97.41-99.47) and 0.72 - 0.94 in phosphate buffer (% Recovery 96.61-98.97) which is less than 2.0 indicating that the methods are accurate.

 

Assay of Ziprasidone capsules

The percentage of purity of Ziprasidone hydrochloride monohydrate was found to be 99.45% and 99.39% in acetate buffer and phosphate buffer and no interference of excipients was observed. The Optical characteristics of the proposed methods were shown in Table 3.

 

Table 3: Optical characteristics

Parameters

Method

Method I

Method II

Linearity range (µg/mL)

0.5 - 30

1 - 120

λmax (nm)

315.00

315.40

Molar extinction coefficient

(liter/mole/cm-1)

7.15153 x 103

13.186 x 103

Sandell’s sensitivity

(µg/cm2/0.001absorbance unit)

0.0654

0.0355

Slope

0.0154

0.0266

Intercept

0.0002

0.0162

Correlation coefficient

0.9997

0.9998

Precision (% RSD)

Intraday

1.0072

1.3036

Inter day

1.9226

1.3937

Accuracy (% RSD)

0.76-0.98

0.72-0.94

Assay (%)

99.45

99.39

 

CONCLUSION:

The two new spectrophotometric methods are simple, precise and accurate and these methods can be successfully applied for the determination of Ziprasidone hydrochloride monohydrate in pharmaceutical dosage forms.

 

ACKNOWLEDGEMENT:

The authors are grateful to GITAM (Deemed to be University), Visakhapatnam for providing the research facilities and Torrent pharmaceuticals (India) for providing the gift samples of Ziprasidone hydrochloride monohydrate.

 

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Received on 14.01.2022           Modified on 12.03.2022

Accepted on 14.05.2022         © RJPT All right reserved

Research J. Pharm. and Tech. 2022; 15(7):3209-3212.

DOI: 10.52711/0974-360X.2022.00538