A REVIEW ON ANALYTICAL METHODS FOR DETERMINATION OF LEVOSULPIRIDE IN PHARMACEUTICAL DOSAGE FORMS AND BIOLOGICAL SAMPLE

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ABOUT AUTHORS:
Monika A. Rana*, Hasumati A. Raj
Department of Quality Assurance
Shree Dhanvantary College of Pharmacy,
Kim, Gujarat, India
monika92rana@gmail.com

ABSTRACT
Levosulpiride is an atypical antipsychotic agent. Levosulpiride is the levo enantiomer of sulpiride. It is a substitute benzamide which is meant to be used for several indications: depression, psychosis, somatoform disorders, emesis anddyspepsia. It blocks the presynaptic dopaminergic D2 receptor. Chemically it is N-[[(2S)-1-Ethylpyrrolidin-2-yl] methyl]-2-methoxy-5 sulfamoylbenzamide. several method such as HPLC in human plasma, area under curve, stability by RP-HPLC is done. The parent drug is given in a dose of 400-1800 mg orally. According to literature survey study of impurity profiling of LIVOSULPIRIDE in presence of intermediate has not been reported.

REFERENCE ID: PHARMATUTOR-ART-2278

PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 11

Received On: 23/09/2014; Accepted On: 26/09/2014; Published On: 01/11/2014

How to cite this article: MA Rana, R Hasumati; A Review on Analytical Methods for Determination of Levosulpiride in Pharmaceutical Dosage Forms and Biological Sample; PharmaTutor; 2014; 2(11); 66-74

INTRODUCTION[1-2]
Levosulpiride is the levo enantiomer of sulpiride. sulpiride contain NLT 98.5% and NMT the equivalent of 101.0 % of (RS)-5-sulphamoly-N-[(1-ethylpyrrolidine-2-yl)methyl]-2-methoxybenzamide. Levosulpiride is N-[[(2S)-1-Ethylpyrrolidin-2-yl] methyl]-2-methoxy-5 sulfamoylbenzamide. It is anti psychotic agent. It is almost white, crystalline power. The plasma t1/2 of the drug is about 6-8 hours. The drug is chiefly excreted through the renal route. Its chemical structure is as follows:


Figure No:1 Levosulpiride

TABLE NO: 1 Reported Analytical Methods for LEVOSULPIRIDE in Pharmaceutical Dosage form and Active Pharmaceutical Ingredient.

Drug /Drug combination

Matrix

Method

Description

Ref.No

Levosulpiride

Pharmaceutical dosage form

UV spectrophotometry, Derivative spectroscopy

Levosulpiride was estimated at 291 nm in 0.1N NaOH (Method A), 288.7 nm in Methanol (Method B) and first order derivative spectrum in Methanol at 282.4 nm with n=1 (Method C). Linearity range was found to be 25-125 μg/ml in all the three methods. The apparent molar absorptivity was found to be 2.14 X 103 lmol-1cm-1 (Method A), 2.39 X 103 lmol-1cm-1 (Method B) and 2.07 X 103 lmol-1cm-1 (MethodC).

(3)

Levosulpiride

Tablet

Area under curve, difference spectroscopy

AUC in which area under curve was integrated in the wavelength range of 284–294 nm using methanol as solvent. Difference

Spectroscopic method, the proposed method is based on the principle that Levosulpiride can exhibit two different chemical form in basic and acidic medium that differ in the absorption spectra in basic acidic medium. The difference spectrum of Levosulpiride in 0.01N NaOH was recorded by taking Levosulpiride in 0.01N HCL solution as blank. The difference spectrum showed that the maxima at 227nm and minima at 246nm. Linearity for the detector response was observed in the concentration range of 5-25 μg/ml for both the methods. The linear regression for Method A and B were found to be 0.999 and 0.999respectively.

(4)

Levosulpiride

Tablet

HPLC

Peak area ratio of the analyte to internal standard was used for the quantification of serum samples. The study was conducted using an open, randomized crossover design to determine relative bioavailability of levosulpiride tablets (test and reference preparations) in twelve healthy male volunteers following single oral administration. The pharmacokinetic parameters like area under the plasma-concentration-time curve from zero to the last measurable levosulpiride sample time and to infinity (AUC0-t and AUC0-∞), maximum concentration (Cmax), time to maximum concentration (Tmax), and elimination rate constant (Ke) and elimination half-life (T1/2) were determined by non compartmental method. The bioequivalence between the two formulations was assessed by calculating individual peak plasma concentration (Cmax) and area under the curve (AUC0-t) ratio (Test/Reference). The assay showed excellent relationships between peak height ratios and plasma concentrations (r2 ≥ 0.9925). The geometric mean of Levosulpiride 100 mg tablet (test/ reference) individual percentage ratio was 100% for AUC0-t and 99% for Cmax. The 90% confidence intervals were 99.2-100.1% and 98.4-99.9%, respectively. The relative bioavailability between test and reference was 99.54%. Since the 90% CI for both AUC0-α, and Cmax lies within the 80-125% proposed by the FDA, it was concluded that both preparations of levosulpiride 100 mg tablets were bioequivalent in terms of both the rate and extent of absorption.

(5)

Levosulpiride HCL

Tablet


Stability Indicating

RP-HPLC

A sunfire C-18, 4.5mm column with mobile phase containing methanol-water (10:90, v/v) was used. The flow rate was 1.0 mL min-1 and effluents were monitored at 232 nm. The retention time of Levosulpiride was 5.5 min. Levosulpiride stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation, wet hydrolysis, dry heat degradation and sun light degradation. The degraded product peaks were well resolved from the pure drug peak with significant difference in their retention time values. Stressed samples were assayed using developed LC method.


(6)

Levosulpiride

Tablet

Stability Indicating HPTLC

In this method mobile phase consisting of ethyl acetate:methanol:toluene: triethylamine (4.5:3.5:2: 0.2v/v/v/v) and detection was carried out at 238 nm. Linearity was observed over the concentration range 100 500 ng/spot. Levosulpiride was subjected to stress conditions including acidic, alkaline, oxidation and photolytic degradation. Levosulpirideis more sensitive towards alkaline degradation. The content of levosulpiride in marketed formulation was found to be 99.13 %±0.38 of labeled amount.

(7)

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