vii LIST OF TABLES TABLE NO DESCRIPTION PAGE 1.1 System Suitability Parameters and Recommendations Acidic and Alkaline Hydrolysis 15

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1 vii LIST OF TABLES TABLE NO DESCRIPTION PAGE CHAPTER System Suitability Parameters and Recommendations Acidic and Alkaline Hydrolysis Oxidative Degradation Study Hydrolysis under neutral conditions 17 CHAPTER List of Materials List of Instruments 59 CHAPTER Oxaprozin spiking standard dilutions Oxaprozin standard solutions for Quality Control Samples 4.3 Oxaprozin plasma calibration curve standards by spiking solutions and pooled human plasma 4.4 Oxaprozin plasma quality control samples using pooled human plasma 4.5 Aqueous SSC (Spiking Solution Check) Calibration Standards 4.6 Aqueous SSC (Spiking Solution Check) Quality control standards 4.7 Calibration curve standards of Tolperisone hydrochloride in methanol

2 TABLE NO DESCRIPTION PAGE 4.8 Calibration curve standards of Tolperisone hydrochloride in human plasma Quality control (QC) samples of Tolperisone hydrochloride 94 CHAPTER Metoprolol succinate calibration standard concentrations Telmisartan calibration standard concentrations System suitability parameters Results of mixed standard solution Tablet formulation analysis Statistical validation of tablet formulation Precision Study Results of Recovery Studies Statistical validation of Recovery Studies Results of Robustness Study % content of MET and TEL in mixed standard for Forced Degradation Study Results of forced degradation study in mixed standard Results of forced degradation study in tablet formulation Metoprolol succinate calibration standard concentration Olmesartan medoxomil calibration standard concentrations 129

3 TABLE NO DESCRIPTION PAGE 5.16 System Suitability Parameters Results of mixed standard solution Tablet formulation Analysis Statistical validation of Tablet Formulation Precision Study Results of Recovery studies Statistical validation of recovery studies Results of Robustness study % content of MET and OLM in mixed standard for Forced degradation study 5.25 Forced degradation study of MET and OLM in mixed standard 5.26 Forced degradation study of MET and OLM in tablet mixture 5.27 Peak area ratio for linearity of Oxaprozin standards in aqueous solvent Oxaprozin calibration curve standards in Human Plasma Result of Intraday Precision and Accuracy Result of Interday Precision and Accuracy Results of Matrix effect of Oxaprozin and Ibuprofen 165 in Human Plasma 5.32 Recovery of Oxaprozin in human plasma 166

4 TABLE NO DESCRIPTION PAGE 5.33 Recovery of Ibuprofen in human plasma Statistical validation of recovery of Oxaprozin and Ibuprofen in human plasma 5.35 Results of Bench Top Stability Oxaprozin in human plasma 5.36 Results of Autosampler stability Oxaprozin in human plasma 5.37 Results of Freeze Thaw stability Oxaprozin in human plasma 5.38 Calibration curve standards of Tolperisone hydrochloride in Methanol 5.39 Calibration curve standards of Tolperisone hydrochloride in human plasma Results for Selectivity of Tolperisone Hydrochloride Intraday Precision and accuracy of QC samples of Tolperisone hydrochloride in human plasma 5.42 Interday Precision and accuracy of QC samples of Tolperisone hydrochloride in human plasma Recovery of QC samples of Tolperisone hydrochloride 181 (Analyte) in human plasma 5.44 Recovery of Eperisone in human plasma Statistical validation of recovery of Tolperisone hydrochloride and Eperisone in human plasma 5.46 Short term stability study of QC samples of Tolperisone hydrochloride in human plasma

5 TABLE NO DESCRIPTION PAGE 5.47 Long term stability study of QC samples of Tolperisone hydrochloride in human plasma 5.48 Freeze thaw stability study of QC samples of Tolperisone hydrochloride in human plasma CHAPTER Summary of Validation Parameters of RP HPLC Method for Simultaneous estimation of Metoprolol Succinate and Telmisartan 7.2 Summary of Validation Parameters of RP HPLC Method for Simultaneous estimation of Metoprolol Succinate and Olmesartan medoxomil 7.3 Summary of Validation Parameters of Bioanalytical method development for estimation of Oxaprozin 7.4 Summary of Validation Parameters of Bioanalytical method development for estimation of Tolperisone hydrochloride in human plasma by HPLC

6 viii LIST OF FIGURES FIG. No. DESCRIPTION PAGE CHAPTER Classification of Chromatographic Methods Fundamental Parameters of Chromatography Resolution between two peaks Flow Diagram of HPLC Hydrolytic degradation study under acidic and alkaline conditions Oxidative degradation study Photolytic degradation study Neutral hydrolysis Flow chart of Bioanalytical Method Development CHAPTER- 5 UV spectrum of Metoprolol succinate UV spectrum of Telmisartan Metoprolol succinate (MET) calibration curve Telmisartan (TEL) Calibration curve

7 FIG. No. DESCRIPTION PAGE Chromatogram of standard MET (50 µg/ml) Chromatogram of standard TEL (40 µg/ml) Chromatogram of 50 µg/ml of MET and 40 µg/ml of TEL mixed standard Chromatogram of 50 µg/ml of MET and 40 µg/ml of TEL in tablet formulation Acidic degradation chromatogram of MET in 0.1N HCl Acidic degradation chromatogram of TEL in 0.1N HCl Acidic degradation chromatogram of MET and TEL mixed standard in 0.1N HCl Acidic degradation chromatogram of MET and TEL tablet mixture in 0.1N HCl Alkali degradation chromatogram of standard MET in 1N NaOH Alkali degradation chromatogram of standard TEL in 1N NaOH Alkali degradation chromatogram of standard mixture of MET and TEL in 1N NaOH Alkali degradation chromatogram of MET and TEL tablet mixture in 1N NaOH Degradation Chromatogram of standard MET in neutral Condition Degradation chromatogram of standard TEL in neutral Condition

8 FIG. No. DESCRIPTION PAGE Degradation chromatogram of MET and TEL standard mixture in neutral condition Degradation Chromatogram of MET and TEL Tablet mixture in neutral condition Oxidative degradation chromatogram of standard MET Oxidative degradation chromatogram of standard TEL Oxidative degradation chromatogram of MET and TEL standard mixture Oxidative degradation chromatogram of MET and TEL tablet mixture Dry heat degradation chromatogram of MET Dry heat degradation chromatogram of TEL Dry heat degradation chromatogram of MET and TEL Dry heat degradation chromatogram of MET and TEL Tablet mixture Photolytic degradation Chromatogram of MET Photolytic degradation Chromatogram of TEL Photolytic degradation chromatogram of MET and TEL standard mixture Photolytic degradation chromatogram of MET and TEL tablet mixture UV spectrum of olmesartan medoxomil Metoprolol succinate (MET) calibration curve

9 FIG. No. DESCRIPTION PAGE Olmesartan medoxomil (OLM) calibration curve Chromatogram of standard MET (50 µg/ml) Chromatogram of standard OLM (40 µg/ml) Chromatogram of 50 µg/ml of MET and 40 µg/ml of OLM mixed standard Chromatogram of 50 µg/ml of MET and 40 µg/ml of TEL in tablet formulation Acidic degradation chromatogram of MET in 0.1N HCl Acidic degradation chromatogram of OLM in 0.1N HCl Acidic degradation chromatogram of MET and OLM mixed standard in 0.1N HCl Acidic degradation chromatogram of MET and OLM tablet mixture in 0.1N HCl Alkali degradation chromatogram of standard MET in 1N NaOH Alkali degradation chromatogram of standard OLM in 1N NaOH Alkali degradation chromatogram of MET and OLM standard mixture of in 1N NaOH Alkali degradation chromatogram of MET and TEL tablet mixture in 1N NaOH Degradation Chromatogram of standard MET in neutral condition

10 FIG. No. DESCRIPTION PAGE Degradation chromatogram of standard OLM in neutral condition Degradation chromatogram of MET and OLM mixed standard in neutral condition Degradation Chromatogram of MET and OLM Tablet mixture in neutral condition Oxidative degradation chromatogram of standard MET Oxidative degradation chromatogram of standard TEL Oxidative degradation chromatogram of MET and OLM mixed standard Oxidative degradation chromatogram of MET and TEL tablet mixture Dry heat degradation chromatogram of MET Dry heat degradation chromatogram of OLM Dry heat degradation chromatogram of MET and OLM Mixed standard Dry heat degradation chromatogram of MET and OLM Tablet mixture Photolytic degradation Chromatogram of MET under UV light Photolytic degradation chromatogram of OLM under UV light 5.62 Photolytic degradation chromatogram of MET and OLM mixed standard 5.63 Photolytic degradation chromatogram of MET and TEL tablet mixture 5.64 UV spectrum of Oxaprozin

11 FIG. No. DESCRIPTION PAGE Oxaprozin calibration curve standards in aqueous media Oxaprozin calibration curve standards in human plasma Chromatogram of 120 µg/ml of Oxaprozin in aqueous solution by LC-MS method Chromatogram of LOQQC sample of Oxaprozin in Human Plasma by LC-MS method Chromatogram of LQC sample of Oxaprozin in Human Plasma by LC-MS method Chromatogram of MQC sample of Oxaprozin in Human Plasma by LC-MS method Chromatogram of LMQC sample of Oxaprozin in Human Plasma by LC-MS method Chromatogram of HQC sample of Oxaprozin in Human Plasma by LC-MS method UV Spectrum of Tolperisone hydrochloride Typical chromatogram of 2000 ng/ml TOL in methanol Calibration curve of TOL in methanol Calibration curve of TOL in human plasma Typical chromatogram of Blank Plasma Typical chromatogram of LLOQ sample of TOL in plasma Typical chromatogram of LQC sample of TOL in human plasma Typical chromatogram of MQC sample of TOL in human plasma Typical chromatogram of HQC sample of TOL in human plasma

12 ix List of Abbreviations HPLC High performance liquid chromatography RP-HPLC Reverse Phase High performance liquid chromatography LC-MS HETP T Rs t R N UV PDA AR N MET TEL OLM OXA IBU TOL EPE HCl NaOH H 2O 2 mg Liquid Chromatography Mass Chromatography Height equivalent to theoretical plate Tailing Factor Resolution Retention Time Theoretical Plates Ultra-violet Photodiode array detector Analytical grade Normality Metoprolol succinate Telmisartan Olmesartan medoxomil Oxaprozin Ibuprofen Tolperisone hydrochloride Eperisone hydrochloride Hydrochloric acid Sodium hydroxide Hydrogen peroxide Milligram µg Microgram

13 ng ml Nanogram Milliliter µl Microlitre mm Millimoles µ Micron nm AUC 0C RPM BMV LOD LOQ LLOQ LQC MQC LMQC HQC CV SD RSD hr λmax NLT m/z Nanometer Area under curve Degree centigrade Revolution per minute Bioanalytical method validation Limit of detection Limit of quantitation Lower Limit of Quantification Low quality control Middle quality control Limit middle quality control High quality control Coefficient of variation Standard deviation Relative standard deviation Hours Maximum wavelength Not less than Mass to charge ratio