Only 14 pages are availabe for public view
The Thesis is concerned with the development and validation of stability indicating methods for the analysis of meclofenoxate hydrochloride (MFX) drug and its hydrolytic degradation product, p-chlorophenoxyacetic acid (pCPA), in bulk powder, pharmaceutical dosage forms using HPLC-DAD-FL and HPTLC methods. In addition; this work concerned with development and validation of spectrophotometric and spectrofluorimetric methods for the determination of MFX and pCPA in bulk powder, pharmaceutical dosage forms after LLE/SPE step. All the developed methods were validated according to ICH guidelines.
Furthermore; HPLC-DAD-FL and HPTLC methods were developed and optimized for the determination of pCPA in plasma and urine. Extensive study was conducted to determine the bioanalytical pharmacokinetics parameters after oral administration of 250 mg Lucidril® tablet to healthy volunteers.
These developed methods were validated according to FDA bioanalytical method validation guidelines.
Chapter I This chapter contains a general introduction about the central nervous system disorders and medications as well as the classification of psychotropic drugs. Furthermore; it contains a general introduction about the chemical name, structure, physical properties, molecular formulae, molecular weight, pharmacological action, therapeutic uses of the studied drug and a literature review of the methods that have been reported for the analysis of MFX in bulk powder, pharmaceutical dosage form as well as in biological fluids.
Chapter II This chapter deals with the development and validation of a stability indicating HPLCdiode array-fluorescence method for the determination of MFX and its hydrolytic degradation product, pCPA. The chromatographic separation was achieved using a reversed phase Zorbax Eclipse SB-C18 column (250 x 4.6 mm i.d., 5 μm particle size), a mobile phase composed of 20 mM phosphate buffer, adjusted to pH 3, and acetonitrile (65: 35, v/v); and isocratic flow at a rate of 1 mL min-1. The detection was carried out using a diode array detector (DAD) at 225 nm and a fluorescence detector (FL) at λex/em = 225/310 nm. MFX and pCPA retention times were 3.81 ± 0.06 and 9.82 ± 0.08 min, respectively.The linear dynamic ranges were found to be 0.5-100 μg mL-1 (DAD) and 0.05-20 μg mL-1 (FL) for MFX and; 0.25-100 μg mL-1 (DAD) and 0.01-8 μg mL-1 (FL) for pCPA. Detection limits were 0.05 μg mL-1 (DAD) and 0.005 μg mL-1 (FL) for MFX and; 0.04 μg mL-1 (DAD) and 0.001 μg mL-1 (FL) for pCPA.
The method was applied to study the forced hydrolytic, oxidative and photolytic degradation of MFX. It should be noted that the other reported methods have considered only the hydrolytic degradation and no HPLC-fluorescence detection method has been reported for the determination of MFX or pCPA.