RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,



RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

| | |SK SULTHAN BASHA |

|1. |Name of the Candidate | |

| |and Address |a. Permanent Address |

| | |S/O SK Khaleel |

| | |Kothapatnam |

| | |Prakasam district- 523286 |

| | |Andhra Pradesh. |

| | |b. Postal Address |

| | |Krupanidhi College of Pharmacy |

| | |Chikka Bellandur, |

| | |Carmelaram Post, Varthur Hobli, |

| | |Bangalore-35 |

| | |Karnataka. |

|2. |Name of the Institute | Krupanidhi College of Pharmacy |

| | |Chikka Bellandur, Carmelaram Post, |

| | |Varthur Hobli, |

| | |Bangalore – 560035 |

| | |Karnataka. |

|3. |Course of Study and Subject | Master of Pharmacy in |

| | |Pharmaceutical Analysis |

|4. |Date of Admission to Course | 18/06/2011 |

|5. |Title of the Topic: |

| |“METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF LOSARTAN POTASSIUM AND METOLAZONE IN COMBINED DOSAGE FORM BY HPLC AND UV |

| |SPECTROSCOPY” |

| |BRIEF RESUME OF THE INTENDED WORK |

|6 | |

| |6.1 Need of study: |

| |The main aim of this work is to develop and validate a relatively simple method for simultaneous estimation of losartan potassium and |

| |metolazone in combined dosageform by using RP-HPLC and UV spectroscopy technique. |

| |[pic] |

| | |

| |[pic] |

| | |

| | |

| | |

| |Losartan potassium is chemically potassium 2 - Butyl -4- chloro - 1 -[[2′ - (1H - tetrazol - 5 - yl)[1,1′ -biphenyl] -4- yl] - methyl] - 1H|

| |- imidazole - 5 - methanol monopotassium salt 3. It is a strong non-peptide antihypertensive agent, which exerts its action by specific |

| |blocking of angiotensin II receptors. It has a gradual, long-lasting effect as an antihypertensive. |

| | |

| |Metolazone is chemically 7-chloro-2-methyl-4-oxo-3-o-tolyl-1,2,3,4 tetrahydroquinazoline-6-sulfonamide4-5. Metolazone is an oral diuretic |

| |drug, commonly classified with the thiazide diuretics. It is primarily used to treat congestive heart failure and high blood pressure. |

| |Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine|

| |volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. |

| | |

| |Hence, the combination of losartan potassium and metolazone, such as in the marketed product and provides an additive effect on blood |

| |pressure control. |

| |In the proposed project, the validation of the combination is done using liquid chromatographic and spectroscopic methods. |

| |Many mathematical models have been suggested for the estimation of interference from excipients and other drugs present in the formulation |

| |so that the analyte can be estimated without the necessity of prior separation step like extraction. Many of the methods can be used for |

| |the simultaneous estimation of multicomponent formulation also, of which RP-HPLC method is the best known. |

| | |

| |Reverse phase HPLC6 (RP-HPLC or RPC) has a non-polar stationary phase and an aqueous or moderately polar mobile phase. One common |

| |stationary phase is silica which has been treated with RMe2SiCl, where R is a straight chain alkyl group such as C18H37 or C8H17. With |

| |these stationary phases, retention time is longer for molecules which are less polar, while polar molecules elute more readily. An |

| |investigator can increase retention time by adding more water to the mobile phase; thereby making the affinity of the hydrophobic analyte |

| |for the hydrophobic stationary phase stronger relative to the now more hydrophilic mobile phase. Similarly, an investigator can decrease |

| |retention time by adding more organic solvent to the eluent. RPC is so commonly used that it is often incorrectly referred to as "HPLC" |

| |without further specification. The pharmaceutical industry regularly employs RPC to qualify drugs before their release. |

| |The literature survey reveals the need for an efficient method for the simultaneous estimation of losartan potassium and metolazone. In |

| |view of the need for the suitable method for routine analysis in combined formulations, attempts are been made to develop simple, precise |

| |and accurate analytical methods for simultaneous estimation of title ingredients and extend for the determination in formulation by |

| |modifying certain parameters of the experiment. |

| | |

| |6.2 Review of Literature: |

| |Literature review reveals that methods have been reported for analysis of losartan potassium and metolazone, HPLC method for determination |

| |of losartan potassium in combination with other drugs and few bioanalytical methods are also reported. RP-HPLC method for determination of |

| |metolazone and few bioanalytical methods have been reported. |

| | |

| |Gadipalli Sai Kiran7 et al., proposed RP-HPLC method for the determination of losartan potassium and hydrochlorthiazide present in tablet|

| |formulation. A simple, specific, accurate and precise Reverse Phase High Performance Liquid Chromatographic method was developed for |

| |simultaneous estimation of losartan potassium and hydrochlorothiazide (HTZ) in tablet dosage form on RP C-18 Column (BDS Hypersil 250*4.6 |

| |mm) using acetonitrile: water(50:50) as mobile phase. The flow rate was 1.0 ml/min and effluent was monitored at 232nm. The retention time |

| |for losartan potassium and HTZ was found to be as 1.98 and 3.04 respectively. Proposed method was validated for precision, accuracy, |

| |linearity range, robustness and ruggedness. |

| | |

| |A.I.Patel8 et al., proposed RP-HPLC method for the determination of losartan potassium and perindopril erbumine in combined tablet dosage |

| |form. A simple, fast, and precise reverse phase high performance liquid chromatographic method was developed and validated for the |

| |simultaneous estimation of losartan potassium and perindopril erbumine in its tablet form. The HPLC method involved by using hiqsil-C-18W |

| |ODS, (250 mm × 4.5 mm i.d.), 5 column and mobile phase was ACN: water in proportion of 50:50 v/v, pH adjusted to 3.2 ± 0.1 with 1 % |

| |o-phosphoric acid. The flow rate was 1.0 ml/min and effluent was monitored at 210 nm. The retention time of losartan potassium and |

| |perindopril erbumine were eluted at 6.7 min and 4.5 min respectively. The method was validated in terms of linearity, precision, accuracy, |

| |limit of detection. The method was found to be linear in the range of 2-18 gml-1 for both the drug. The coefficient of variance for both |

| |the drug was more than 0.999. The mean percentage recovery was found to be 98.40 % for losartan potassium and 97.50 % for perindopril |

| |erbumine. The limits of quantification of losartan potassium and perindopril erbumine were found to be 0.109 g/ml and 0.041 g/ml. The |

| |method has been successfully applied for determination of losartan potassium and perindopril erbumine in combined dosage form. |

| |Choi9 and his coworkers proposed a sensitive, simple, rapid, and specific liquid chromatography electrospray ionization mass spectrometry |

| |(LC-ESI-MS) method for determination of losartan in human plasma was developed and validated for the identification and quantification of |

| |losartan in a small volume of human plasma. Losartan and I.S. were successfully separated on a CN column with a mobile phase of |

| |acetonitrile-0.2% formic acid solution (68:32, v/v). Detection was performed on a single quadrupole mass spectrometer by a selected ion |

| |monitoring (SIM) mode via electrospray ionization (ESI) source. The ESI source was set at positive ionization mode. The ion signal of m/z|

| |422.79 and 194.81 were measured for losartan and I.S., respectively. The limit of detection (LOD) was 0.5 ng/mL (signal-to-noise ratio of |

| |10.03) using only 200 μL of human plasma samples. The calibration curve was an excellent linear fit over the range of concentrations |

| |1.0-1000 ng/mL (R2 = 0.9987) of losartan in human plasma. Consequently, all results fulfilled the common standard criteria of |

| |bioequivalence, 0.80 to 1.25 by the Korean and US Food and Drug Administration. In addition to the confidence intervals (C.I.) 90% of the |

| |pharmaceutical parameters, a two-way ANOVA showed no significant difference between the two formulations. This method was successfully |

| |applied to bioequivalence study of two brands of losartan potassium tablet (100 mg) formulations after a single oral administration. |

| | |

| |Wei G, Xiao S10 et.al, demonstrated a rapid, sensitive and accurate liquid chromatographic-tandem mass spectrometric method for the |

| |determination of metolazone in human blood by liquid chromatography with electrospray ionization tandem mass spectrometry. Metolazone was |

| |extracted from blood using ethyl acetate and separated on a C-18 column interfaced with a triple quadruple tandem mass spectrometer. |

| |The mobile phase consisting of a mixture of acetonitrile, 10 m.mol/l ammonium acetate and formic acid (60:40:0.1, v/v/v) was delivered at a|

| |flow rate of 0.5 ml/min. Electrospray ionization (ESI) source was operated in positive ion mode. Selected reaction monitoring (SRM) mode |

| |using the transitions of m/z 366-->m/z 259 and m/z 321-->m/z 275 were used to quantify metolazone and the lorazepam (internal standard), |

| |respectively. The linearity was obtained over the concentration range of 0.5-500 ng/ml for metolazone and the lower limit of quantitation |

| |(LOQ) was 0.5 ng/ml. For each level of QC samples, inter- and intra-run precision was less than 8.07 and 3.56% (relative standard deviation|

| |(RSD), respectively, and the bias was within +/-4.0%. This method was successfully applied to the pharmacokinetic study of metolazone |

| |formulation after oral administration to humans. |

| | |

| |Priyanka R patil11 proposed two simple, accurate, precise, reproducible, requiring no prior separation and economical procedures for |

| |simultaneous estimation of losartan potassium and amlodipine besylate in tablet dosage form have been developed. First method employs |

| |formation and solving of simultaneous equation using 208 nm and 237.5 nm as two analytical wavelengths for both drugs in methanol. The |

| |second method is Q-value analysis based on measurement of absorptivity at 242.5 nm (as an iso-absorptive point) and 237.5 nm. Losartan |

| |potassium and amlodipine besylate at their respective λmax of 208 nm and 237.5 nm and at isoabsorptive point 242.5 nm shows linearity in a |

| |concentration range of 2-20 g/ml. Recovery studies range from 99.95% for losartan potassium and 99.33% for amlodipine besylate in case of |

| |simultaneous equation method and 102.93% for losartan potassium and 101.02% for amlodipine besylate in case of Q - analysis method |

| |confirming the accuracy of the proposed method. |

| | |

| |Shah SA12 and his co-workers proposed Simultaneous determination of losartan and hydrochlorothiazide in combined dosage forms by |

| |first-derivative spectroscopy and high-performance thin-layer chromatography. Losartan (LST) is the first orally active nonpeptide |

| |angiotensin-II receptor antagonist with an improved safety and tolerability profile. It is prescribed alone or in combination with |

| |hydrochlorothiazide (HCTZ) for the treatment of moderate-to-severe hypertension. This paper describes the development of 2 methods that |

| |use different techniques, first-derivative spectroscopy and high-performance thin-layer chromatography (HPTLC), to determine LST and HCTZ |

| |in the presence of each other. LST and HCTZ in combined preparations were quantitated by using the first-derivative responses at 271.6 nm |

| |for LST and 335.0 nm for HCTZ in spectra of their solutions in water. The linearity ranges are 30-70 µg/mL for LST and 7.5-17.5 µg/mL for |

| |HCTZ with correlation coefficients of 0.9998 and 0.9997, respectively. In the HPTLC method, a mobile phase of |

| |chloroform-methanol-acetone-formic acid (7.5 + 1.5 + 0.5 + 0.03, v/v) and a prewashed silica gel G60 F254 TLC plate as the stationary phase|

| |were used to resolve LST and HCTZ in a mixture. Two well-separated and sharp peaks for LST and HCTZ were obtained at Rf values of |

| |0.61+/-0.02 and 0.41+/-0.02, respectively. LST and HCTZ were quantitated at 254.0 nm. The linearity ranges obtained for the HPTLC method |

| |are 400-1200 and 100-300 ng/spot with corresponding correlation coefficients of 0.9944 and 0.9979, for LST and HCTZ, respectively. Both |

| |methods were validated, and the results were compared statistically. They were found to be accurate, specific, and reproducible. The |

| |methods were successfully applied to the estimation of LST and HCTZ in combined tablet formulations. |

| | |

| |Jitendra A. Wayadande13 and his workers proposed validated HPTLC Method for simultaneous estimation of ramipril and metolazone in bulk drug|

| |and formulation proposed this paper describes a new, simple, precise, and accurate HPTLC method for simultaneous estimation of ramipril and|

| |metolazone as the bulk drug and in tablet dosage forms. Chromatographic separation of the drugs was performed on aluminum plates precoated |

| |with silica gel 60 F254 as the stationary phase and the solvent system consisted of toluene : ethylacetate : methanol : glacial acetic acid|

| |(4 : 4 : 1 : 0.2 v/v/v/v). Densitometric evaluation of the separated zones was performed at 223 nm. The two drugs were satisfactorily |

| |resolved with Rf values 0.33 ± 0.02 and 0.59 ±0.02 for ramipril and metolazone respectively. The accuracy and reliability of the method |

| |was assessed by evaluation of linearity (600-2100 ng/spot for ramipril and 100-350 ng/spot for metolazone, precision (intra-day % RSD was |

| |1.28 – 1.58 and inter-day % RSD was 1.14 – 1.83 for ramipril and intra-day % RSD was 0.67 – 1.03 and inter-day % RSD was 0.49 – 1.18 for |

| |metolazone), accuracy 99.44 ± 0.15 for ramipril and 99.85 ± 0.39 for metolazone), and specificity in accordance with ICH guidelines. |

| | |

| | |

| |T.siva Kumar14 and his co-workers proposed development of a HPLC method for the simultaneous determination of losartan potassium and |

| |atenolol in tablets. A new reversed-phase high performance liquid chromatography method was developed and validated for the simultaneous |

| |determination of losartan potassium and atenolol in tablets. The separation was achieved on supelcosil ODS analytical column (25×0.46 cm, |

| |i.d., 5 µm) using acetonitrile and 25 mM potassium dihydrogen phosphate (45:55 v/v, pH 3.00±0.05) as mobile phase at a flow rate of 1.2 |

| |ml/min. Detection was carried out using a UV detector at 227 nm. The method was validated. The developed and validated method was |

| |successfully applied for the quantitative analysis of Losar beta® tablets. The total chromatographic analysis time per sample was about 6 |

| |min with atenolol, chlorzoxazone (internal standard) and losartan eluting at retention times of about 2.72, 4.89 and 5.61 min, |

| |respectively. The standard curves were linear over the concentration ranges, 1-10 µg/ml for losartan potassium and atenolol. The values |

| |obtained of LODs were 0.029 and 0.062 µg/ml and LOQs were 0.078 and 0.187 µg/ml for losartan potassium and atenolol, respectively. The |

| |proposed method is fast, accurate and precise for the determination of losartan potassium and atenolol for routine quality control of |

| |tablets containing these two drugs. |

| | |

| |K.srinivas Rao15 proposed RP-HPLC method for the determination of losartan potassium and ramipril in combined dosage form. A simple, |

| |specific and accurate reverse phase liquid chromatographic method was developed for the simultaneous determination of losartan potassium |

| |and ramipril in table dosage forms. A hypersil ODS C18, 4.6×250 mm, 5 µm column in isocratic mode, with mobile phase acetonitrile: |

| |methanol: 10 mM tetra butyl ammonium hydrogen sulphate in water in the ratio of 30:30:40% v/v/v was used. The flow rate was 1.0 ml/min and |

| |effluent was monitored at 210 nm. The retention times of losartan potassium and ramipril were 4.7 and 3.3 min, respectively. The linearity |

| |range for losartan potassium and ramipril were in the range of 0.04-100 µg/ml and 0.2-300 µg/ml, respectively. The proposed method was also|

| |validated and successfully applied to the estimation of losartan potassium and ramipril in combined tablet formulations. |

| |Muralidharan selvadurai16 et al. proposed sensitive and accurate estimation of losartan potassium formulation by high-performance |

| |thin-layer chromatography. To develop a simple, sensitive, cost-effective and reproducible UV-spectroscopic method and validate for the |

| |estimation of disodium edetate in topical gel formulations. Solution of disodium edetate reacts with ferric chloride to form complex in |

| |0.1 N HCl giving λmax at 270 nm. Beer's law was obeyed in the concentration range of 5-50 μg/mL (r2 = 0.9997). The limit of detection and |

| |limit of quantitation were found to be 1.190 and 3.608 μg/mL, respectively. The results show that the procedure is accurate, precise, and |

| |reproducible (relative standard deviation < 1%), while being simple and less time consuming. The study concluded that the UV-spectroscopic|

| |method could be used for the quantification of disodium edetate in pure form as well as in pharmaceutical formulations. |

| |S.V.S.G.B.Prasad17 et al., proposed LC/MS/MS method for the simultaneous estimation of losartan potassium and irbesartan in rat plasma. A |

| |rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for simultaneous |

| |quantification of Losartan potassium (LOS) and Irbesartan (IRB) in rat plasma using phenomenex polar RP 80 4μ.The mass transition ion-pair|

| |has been followed as m/z 423.4→207.2 for LOS, m/z 429.3→195.1 for IRB. The method involves precipitation extraction from plasma, with |

| |gradient elution chromatographic conditions and mass spectrometric detection using an API 3000 instrument that enables detection at |

| |nanogram levels. Ketoconazole was used as the internal standard. The proposed method has been validated with a linear range of 5.01–1000.8 |

| |ng/ml for LOS and for IRB. |

| | |

| |Aravindraju18 et al proposed a validated RP-HPLC method for simultaneous estimation of losartan potassium and amlodipine in pharmaceutical |

| |formulation. A simple, selective, rapid, precise and economical reverse phase High Pressure Liquid Chromatographic method has been |

| |developed for the simultaneous estimation of losartan potassium and amlodipine besylate from pharmaceutical formulation. The method was |

| |carried out on a Princeton SPHER C18 (15 cm x 4.6 mm i.d., 5) column with a mobile phase consisting of acetonitrile: |

| |dipotassiumorthophosphate (adjusted to pH 7.5 using orthophosphoric acid) (50:50 v/v) at a flow rate of 0.7 ml/min. Detection was carried |

| |out at 239 nm. Diazepam was used as an internal standard. The retention time of losartan, amlodipine and diazepam was 5.36, 3.76 and 15.47|

| |min, respectively. The developed method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantitation|

| |and solution stability. The proposed method can be used for the estimation of these drugs in combined dosage forms. |

| |6.3 Objective of study: |

| |The objective of the present study is to develop and validate a simple, precise and rapid high performance liquid chromatography (HPLC) for|

| |simultaneous estimation of losartan potassium- metolazone. |

| |SPECIFIC OBJECTIVES: |

| |Step 1- Selection of the HPLC method and initial system. |

| |Step 2- Selection of initial conditions. |

| |Step 3- Selectivity optimization. |

| |Step 5- System optimization. |

| |Method development involves a series of sample steps; based on what is known about the sample, a column and detector are chosen; the sample|

| |is dissolved, extracted, purified and filtered as required; an eluent survey (isocratic or gradient) is run; the type of final separation |

| |(isocratic or gradient) is determined from the survey; preliminary conditions are determined for the final separation; retention efficiency|

| |and selectivity are optimized as required for the purpose of the separation ( quantitative, qualitative or preparation); the method is |

| |validated using ICH guidelines. The validated method and data can then be documented. |

| | |

| |Validation is necessary for the following reasons: |

| |To determine whether the process is under control. |

| |To setup the appropriate in-process control. |

| |Typical analytical parameters according to ICH Q2 (R1)20 guidelines can be used in assay validation include: |

| | |

| |6.3.1 Specificity: |

| |Specificity is the ability to assess unequivocally the analyte in the presence of components that may be expected to be present.  Most |

| |related substance methods will be used in a stability study, and therefore they have to be stability indicating.  Stability indicating |

| |means that the method has sufficient specificity to resolve all related substances and the drug substance from each other. |

| |6.3.2 Quantitation limit and Detection limit: |

| |The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be determined |

| |quantitatively with a suitable precision and accuracy. |

| |The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be detected but not |

| |quantitated as an exact value. |

| |Several approaches for determining QL & DL are: |

| |Visual evaluation. |

| |Signal to noise ratio approach. |

| |Standard deviation of the response and slope. |

| | |

| |6.3.3 Linearity: |

| |The linearity of an analytical procedure is its ability (within a given range) to obtain test results that are directly proportional to the|

| |concentration of analyte in the sample solution.  If the linearity does not support such a wide range of concentration, linearity is |

| |determined from 50% of the ICH reporting level to 150% of the proposed shelf life specifications of the related substance (for the high |

| |–low and external standard methods) as a minimum. |

| | |

| |6.3.4 Accuracy: |

| |The accuracy of an analytical procedure expresses the closeness of agreement between the value that is accepted either as a conventional |

| |true value or as an accepted reference value and the value found.  Accuracy for the area percent method should be established from 50% of |

| |the ICH reporting limit to the nominal concentration of drug substance in the sample solution. |

| |For the high–low and external standard methods, determine accuracy from 50% of the ICH reporting level to 150% of the proposed shelf life |

| |specification of the related substances. |

| |Overall accuracy: |

| |• Matrix effect. |

| |• Sample preparation. |

| |• Calculation error. |

| | |

| |6.3.5 Precision: |

| |Repeatability: |

| |Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed |

| |intra assay precision.  Repeatability of a method can be determined by multiple replicate preparations of the same sample.  This can be |

| |done either by multiple sample preparations (n = 6) in the same experiment or by preparing three replicates at three different |

| |concentrations. |

| |Intermediate Precision: |

| |Intermediate precision expresses, within laboratories variations, different days, different analysts, different equipments and so on. |

| |Reproducibility: |

| |Reproducibility expresses the precision between laboratories (collaborative studies are generally used for standardization of methodology).|

| | |

| |6.3.6 Range: |

| |The range of an analytical procedure is the interval between the upper and lower concentrations (amounts) of analytes in the |

| |sample.  Typically, linearity and accuracy determination covers a wide concentration range (e.g. 50% of the ICH reporting limit to 150% of |

| |specification). |

| | |

| |6.3.7 Robustness: |

| |The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small but deliberate variations in method |

| |parameters and provides an indication of its reliability during normal use. |

| | |

| | |

| | |

|7. |MATERIALS AND METHODS: |

| | |

| |7.1 Source of Data: |

| |Data will be obtained from CD-Rom, Internet facilities, Literatures and related articles from libraries of Krupanidhi College of Pharmacy, |

| |Science direct, Indian Institute of Sciences, ICH and WHO Guidelines and related articles, Government College of Pharmacy etc., and other |

| |Research Publications and Journals. |

| | |

| | |

| |7.2 Method of Collection of Data: |

| |Data will be collected from the following step wise experimental procedures proposed in the study: |

| |1. HPLC conditions |

| |a. HPLC column (lot, age, brand) |

| |b. Mobile-phase composition (pH ± 0.05 unit) |

| |c. HPLC instrument (dwell volume, detection wavelength ± 2 nm, column temperature ± 5°C, flow rate) |

| |2. Sample preparation |

| |a. Sample solvent (pH ± 0.05 unit) |

| |b. Sample preparation procedure (shaking time, different membrane filters) |

| |c. HPLC solution stability |

| |Built-in Robustness in Method procedure: |

| |• Weighing error |

| |• Dilution error |

| |• Sonication |

| |• Mobile phase as sample solvent |

| |• Buffer |

| | |

| |This is to verify that the method performance is not affected by typical changes in normal experiments. Therefore, the variation in method |

| |conditions for robustness should be small and reflect typical day-today variation. |

| | |

| | |

| |7.3 Does the study require any investigation or interventions to be conducted on patients or the human or animals? If so please describe |

| |briefly: |

| |NO. |

| | |

| |7.4 Has ethical clearance been obtained from your institute |

| |Not Applicable. |

| | |

|8 |List of References: |

| |Losartan: Wickipedia the free encyclopedia. Available from (Retrieved on 2011 |

| |December 11). |

| |Losartan:Wikipedia, the free encyclopedia. Available from |

| |Domperidone: Wikipedia, the free encyclopedia. available from (Retrieved on 2011 December |

| |11). |

| |Indian Pharmacopoeia. Controller publication New Delhi 2007; 2: 1319–21. |

| |United States Pharmacopoeia 32. Asian Edition NF27, the official compounds of standards 2009; 2: 813–4. |

| |United States Pharmacopoeia 32. Asian edition NF27, the official compounds of standards 2009; 2: 2961–3. |

| |RP-HPLC: Wickipedia, the free encyclopedia. Available from liquid chromatography(Retrived on |

| |2011 Dec 11). |

| |Sai Kiran G, Rajkamal B. Simultaneous estimation of losartan potassium and hydrochlor thiazide present in tablet formulation by RP-HPLC. |

| |Int. J. Pharm. Tech. 2011;(3) 2452-64. |

| |Patel I, Oza CK, Prajapati JP, Vyas AJ and Mehta P. RP-HPLC method for the determination of losartan potassium and perindopril erbumine |

| |in combined tablet dosage form. Int. J. Pharm. Bio.2011; 2(1):709-15. |

| |Choi, Yoonho, Kim, Jin-Ki, Ban, Eunmi. Determination of losartan in human plasma by liquid chromatography electrospray ionization mass |

| |spectrometry (LC-ESI-MS): application to bioequivalence study. J. Liq. Chomatogr. Related Technol. 2008; 31(17): 2643-56. |

| |Wei G, Xiao S, Liu CJ. Determination of metolazone in human blood by liquid chromatography with electrospray ionization tandem mass |

| |spectrometry. Chromatogr B Analyt Technol Biomed Life Sci. 2007; 845(1):169-73. |

| |Priyanka Patil R, Sachin Rakesh U, Dhabale PN, Burade KB. Simultaneous UV Spectroscopic method for estimation of losartan potassium and |

| |amlodipine besylate in tablet dosage form. Asian J. Research Chem. 2009; 2(1): 183-7. |

| |Shah SA, Rathod IS, Suhagia BN, Savale SS, Patel JB. Simultaneous determination of losartan and hydrochlorothiazide in combined dosage |

| |forms by first-derivative spectroscopy and high performance thin-layer chromatography. J. Associ. Analyt. Commu. Int. 2001; 84(6):1715-23.|

| |Jitendra A, Wayadande, Dubey Ramkumar, Vidhya K, Sunil B, Dhaneshwar R. Validated HPTLC method for simultaneous estimation of ramipril |

| |and metolazone in bulk drug and formulation. Der Pharmacia Sinica 2011; 2 (4): 286-94. |

| |Sivakumar T, Venkatesan P, Manavalan R, Valliappan K. Development of a HPLC method for the simultaneous determination of losartan potassium|

| |and atenolol in tablets. Indian J Pharm Sci. 2007; 69:154-7 |

| |Rao KS, Srinivas K. RP-HPLC method for the determination of losartan potassium and ramipril in combined dosage form. Indian J Pharm Sci |

| |2010; 72:108-11. |

| |Selvadurai M, Meyyanathan SN. Sensitive and accurate estimation of losartan potassium formulation by high-performance thin-layer |

| |chromatography. Indian Pharm. Associ. 2011; 2:95-8. |

| |Prasad SVSGB. LC/MS/MS method for the simultaneous estimation of losartan potassium and irbesartan in rat plasma.Indian J Pharm Tech 2011; |

| |3:2452-64. |

| |Aravindraju, Rajan S, Muralidharan S, Meyyanathan SN, Suresh B. A Validated RP-HPLC Method for Simultaneous estimation Of losartan |

| |potassium and amlodipine in |

| |pharmaceutical Formulation.Indian J. Analyt. Chem 2006;3:66-70. |

| |ICH harmonized tripartite guideline, ICH Q2 (R1), text on validation of analytical procedures. |

| | |

| | | |

|9. |SIGNATURE OF THE CANDIDATE | |

| | | |

| | |(SK.SULTHAN BASHA) |

|10. |REMARKS OF THE GUIDE: |

| |Simultaneous estimation of drug combinations can be carried out effectively and faster with great accuracy and precision by HPLC and UV |

| |spectroscopic method compared to other analytical methods. So the above proposed work is recommended for the necessary approval. |

| | | |

|11. |Name and Designation of | |

| | | |

| |Guide |MR. RANGANATH M.K |

| | |Asst. Prof in Pharmaceutical Analysis, |

| | |Dept of Ph. Analysis, |

| | |Krupanidhi College of Pharmacy, |

| | |Bangalore-560 035. |

| | | |

| |11.2 Signature | |

| | |(RANGANATH M.K) |

| | | |

| |11.3 Head of the Department |Prof. Mrs. NAIRA NAYEEM, |

| | |Head of the department, |

| | |Department of Pharmaceutical Analysis, |

| | |Krupanidhi College of Pharmacy, |

| | |Bangalore – 560035. |

| | | |

| |11.4 Signature | |

| | |

|12. |12.1 Remarks of the Principal: |

| |Simultaneous estimation of drug combinations can be carried out effectively and faster with great accuracy and precision by HPLC and UV |

| |method compared to other analytical methods. So the above proposed work is recommended for the necessary approval. |

| |The program and research undertaken by Sk. Sulthan Basha has potential implication in the field of pharmaceutical analysis hence the |

| |project is recommend and request for clearance and approval. |

| | |

| | | |

| |12.2 Signature | |

| | |Dr. Prem Kumar N |

| | |Dean, |

| | |Krupanidhi college of pharmacy, |

| | |Bangalore – 560035 |

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download