INTRODUCTION:

Ziprasidone hydrochloride monohydrate (CAS 138982-67-9) is a second-generation atypical antipsychotic drug (Figure 1). It is a piperazine derivative with antischizophrenic properties^1-2. 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, spectrophotometry^4-18 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 λ_max 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

Table 2: Linearity of Ziprasidone hydrochloride monohydrate

Conc. (µg/mL)	Acetate buffer	Phosphate buffer
Conc. (µg/mL)	Absorbance at λ_max315.00 nm	Absorbance at λ_max315.40 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
λ_max (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

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

DOI: 10.52711/0974-360X.2022.00538


Figure 2A: Acetate buffer (λ_max315.00 nm)	Figure 2B: Phosphate buffer (λ_max315.40 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