RP-HPLC-DAD metoda za određivanje olmesartan medoksomila kao čiste supstancije i u tabletama izloženih razgradnji

A simple, sensitive and precise RP-HPLC-DAD method was developed and validated for the determination of olmesartan medoxomil (AT-II receptor blocker) in the presence of its degradation products. Olmesartan medoxomil and all the degradation products were resolved on a C18 column with the mobile phase composed of methanol, acetonitrile and water (60:15:25, V/V/V, pH 3.5 by orthophosphoric acid) at 260 nm using a photodiode array detector. The method was linear over the concentration range of 1–18 µg mL 1 and precise with RSD 2.0 for each peak and sensitive with LOD 0.03 µg mL−1 and LOQ 0.1 µg mL−1. The method was used to study the drug degradation behavior under forced conditions. Four degradation products (DP-I, II, III, IV) were formed during the degradation study in 0.1 mol L−1 HCl whereas only DP-I, II and III were formed in water, 0.01 mol L−1 NaOH and 3 % H2O2. No significant thermal or photolytic degradation was observed in solid drug. The method was applied successfully for the assay of olmesartan medoxomil in the tablet dosage form.U ovom radu razvijena je i validirana jednostavna, osjetljiva i precizna RP-HPLC-DAD metoda za određivanje olmesartan medoksomila (inhibitor AT-II receptora) u prisutnosti njegovih razgradnih produkata. Olmesartan medoksomil i razgradni produkti kromatografirani su na C18 koloni uz mobilnu fazu metanol/ acetonitril/vo da (60:15:25 V/V/V; pH 3,5 podešen ortofosfornom kiselinom) pri 260 nm uz detektor s fotodiodnim nizom. Metoda je linearna u koncentracijskom rasponu 1–18 µg mL 1 i precizna s RSD < 1 % tijekom ispitivanja repetabilnosti i intermedijarne ponovljivosti. Povrat od 99,3 ± 0,9 do 100,8 ± 1,2 % dokazuje točnost metode. Razvijena metoda je specifična na što ukazuje kromatografsku rezoluciju veću od 2,0 i osjetljiva (LOD = 0,03 µg mL−1 i LOQ = 0,1 µg mL−1). Metoda je upotrebljena za praćenje razgradnje olmesartan medoksomila u uvjetima potencirane razgradnje. U 0,1 mol L−1 HCl detektirana su četiri razgradna produkta (DP-I, II, III, IV), a u vodi, 0,01 mol L−1 NaOH i 3 % H2O2 samo DP-I, II i III. U čvrstom agregatnom stanju nije primjećena značajna termička ni fotolitička razgradnja ljekovite tvari. Metoda je uspješno primijenjena za određivanje olmesartan medoksomila u tabletama

RP-LC and HPTLC Methods for the Determination of Olmesartan Medoxomil and Hydrochlorothiazide in Combined Tablet Dosage Forms

Two new, rapid, precise, accurate and specific chromatographic methods were described for the simultaneous determination of olmesartan medoxomil and hydrochlorothiazide in combined tablet dosage forms. The first method was based on reversed phase liquid chromatography using an Eurosphere 100 RP C18 column (250 × 4.6 mm ID, 5 μm). The mobile phase was methanol–0.05% o-phosphoric acid (60:40 v/v) at a flow rate of 1.0 mL min−1. Commercially available tablets and laboratory mixtures containing both drugs were assayed and detected using a UV detector at 270 nm. The second method involved silica gel 60 F254 high performance thin layer chromatography and densitometric detection at 254 nm using acetonitrile–ethyl acetate–glacial acid (7:3:0.4 v/v/v) as the mobile phase. Calibration curves ranged between 200–600 and 125–375 ng spot−1 for olmesartan and hydrochlorothiazide, respectively

Development of a selective LC method for the determination of pravastatin sodium

A novel, simple and rapid stability-indicating high-performance liquid chromatographic (HPLC) method for pravastatin sodium (PRA) was successfully developed and validated for the assay of in tablets. Chromatographic separation was achieved isocratically on a C-18 column (150 mm x 4.6 mm) utilizing a mobile phase of methanol-phosphate buffer (pH 7; 0.02 M) (57:43, v/v) at a flow rate of 1.0 mL min(-1) with UV detection at 238 nm. A linear response (r = 0.9999) was observed in the range of 1-5 mu g mL(-1). The method showed good recoveries (100.50%) and the relative standard deviation of intra and inter-day were 1.40%. The method can be used for both quality control assay of pravastatin in tablets and for stability studies as the method separates provastatin from its degradation products and tablet excipients

An HPLC method for the determination of lisinopril in human plasma and urine with fluorescence detection

A selective. sensitive and precise HPLC method with fluorimetric detection has been developed for the assay of lisinopril in human plasma and urine. The clean up of the sample was carried out by solid-phase extraction, firstly with C-18-cartridge and secondly with a silica-cartridge. After a pre-column derivatization with fluorescamine, the reaction mixture was chromatographed on C-18-column with gradient elution, using methanol and 0.02 M phosphate buffer (pH = 3.2). The fluorescamine-lisinopril derivative was detected fluorimetrically by monitoring the emission at 477 nm, with excitation at 383 nm. Linear quantitative response curve was generated over a concentration range of 5-200 ng/ml and 25-1000 ng/ml for plasma and urine samples, respectively. The mean recovery of lisinopril from plasma and urine was 63.41 and 74.08%, respectively. Intra-day and inter-day R.S.D. and R.M.E. values at three different concentrations were assessed. The method was applied for pharmacokinetic study in a healthy volunteer after a single oral dose of 20 mg of the drug. (C) 2004 Elsevier B.V. All rights reserved

Selective LC determination of cabergoline in the bulk drug and in tablets: In vitro dissolution studies

Cabergoline (CAB) is an ergot alkaloid derivative with dopamine agonist activity. A novel, simple, and rapid stability-indicating high-performance liquid chromatographic (HPLC) method for assay of CAB in tablets has been developed and validated. Chromatography was performed on a 4.6 mm i.d. x 250 mm, 5 mu m particle, cyano column with acetonitrile-10 mM phosphoric acid, 35:65 (v/v), containing 0.04% triethylamine, as mobile phase, at a flow rate of 1.0 mL min(-1), and UV detection at 280 nm. Response was a linear function of concentration in the range 0.1-4 mu g mL(-1) (r(2) = 0.9999). The recovery of the method was good (99.45%) and RSD values for intra-day and inter-day precision were 0.24-0.88% and 0.66-1.19%, respectively. The method can be used for quality-control assay of CAB in tablets, for stability studies, and for in vitro dissolution studies

A High-Performance Liquid Chromatographic Method for the Determination of Meropenem in Serum.

In this study, a new, sensitive and selective high-performance liquid chromatographic method was developed for the determination of meropenem (MEM) in human serum. In the developedmethod, C18 column (3.9 × 150 mm, 5 μm) was selected as stationary phase at 30◦C, and methanol:acetic acid solution mixture was used as mobile phase with gradient program. Chromatographic separation was carried out at a flow rate of 1 mL/min, and detection was performed at 300 nm with diode array detector. Doripenem was selected as an internal standard, and the analytes were extracted from serum using protein precipitation method with ortho-phosphoric acid: methanol. Detection wavelength was selected as 300 nm. The developed method was validated according to International Council for Harmonisation (ICH) guidelines. The calibration curve was linear over a concentration range of 4–240 μg/mL with correlation coefficient of 0.9985. The limit of detection and limit of quantification values were found as 0.057 and 0.192 μg/mL, respectively. The validated method was successfully applied for the determination of MEM in human serum samples collected from patient volunteers at different time intervals, and therapeutic drug monitoring of MEM has been investigated

Simultaneous determination of fosinopril and hydrochlorothiazide in tablets by derivative spectrophotometric and high-performance liquid chromatographic methods

Fourth derivative UV-spectrophotometric and high-performance liquid chromatographic (HPLC) methods for simultaneous determination of fosinopril and hydrochlorothiazide in tablets have been developed. Standard solutions were measured at zero crossing wavelengths of 217.7 and 227.9 nm for fosinopril and hydrochlorothiazide, respectively, by fourth derivative spectrophotometric method. Calibration curves were constructed by plotting d(4)A/d lambda (4) values at selected wavelengths against concentrations. HPLC analyses were carried out on C-18 column with gradient elution by using 10 mM H3PO4 and CH3CN as mobile phase. Benazepril was used as internal standard and the substances were detected at 215 nm. Commercially available tablets containing 20 mg fosinopril and 12.5 mg hydrochlorothiazide were analysed by fourth derivative spectrophotometric and HPLC methods. The results were compared statistically at 95% confidence level with each other. There was no significant difference between the mean percentage recoveries and precision of the two methods. (C) 2001 Elsevier Science B.V. All rights reserved

Simultaneous HPLC analysis of olmesartan and hydrochlorothiazide in combined tablets and in vitro dissolution studies

A simple, rapid and reproducible HPLC method was developed and validated for the simultaneous determination of olmesartan (OLM) medoxomil and hydrochlorothiazide (HCT) in combined tablets. Chromatography was carried outon a 4.6 mm LD x 200 mm, 5 pm cyanocolumn with methanol-10 mM phosphoric acid containing 0.1 % triethylamine (pH 2.5, 50:50 v/v) at a flow rate of 1.0 mL min(-1) and UV detector was set at 260 nm. Valsartan (VAL) was used as internal standard (IS). A linear response was observed in the range of 0.2-6 mu g mL(-1) (r(2) = 0.9998) for OLM and 0.1-4 pg mL(-1) (r(2) = 0.9999) for HCT, respectively. The method showed good recoveries (99.56% for OLM and 99.48% for HCT) and the relative standard deviation (RSD) values for intra- and inter-day precision were 0.70-1.59 and 0.80-2.00% for OLM and 1.20-1.37 and 1.63-1.93% for HCT, respectively. The developed method was applied successfully for quality control assay of OLM and HCT in combined tablets and in vitro dissolution studies

Preparation and characterization of doripenem-loaded microparticles for pulmonary delivery

Background: Pneumonia is a bacterial lower respiratory tract infection that has a high morbidity rate. The gram-negative pathogen Pseudomonas aeruginosa is a significant cause of nosocomial infections and ventilator-associated pneumonias and is mainly treated by carbapenems. Doripenem is a carbapenem drug, which has a broad-spectrum antibacterial activity. The aim of this study was to develop doripenem-loaded chitosan microparticles for pulmonary administration to provide more efficient treatment for pneumonia. Methods: Ionotropic gelation and the spray-drying method were used to obtain doripenem-loaded chitosan microparticles with different lactose, trehalose, and L-leucine concentrations. Physicochemical characteristics, in vitro drug release properties, and aerodynamics properties were investigated and in vitro antimicrobial susceptibility tests of the formulations were performed. Assessment of aerodynamic properties of the powders, including Mass Median Aerodynamic Diameter, size distribution, and fine particle fraction (FPF), were performed using a Next Generation Impactor. Cytotoxicity of the fabricated microparticles was assessed using the Calu-3 cell airway epithelial cell line. Results: Optimum microparticles were produced using a combination of ionotropic gelation and spray-drying methods. Spray-dried microparticle production yield was relatively high (74.03%3.88% to 98.23%+/- 1.70%). Lactose, trehalose, and L-leucine were added to the formulation to prevent aggregation produced by the ionotropic gelation spray-drying method. Each formulation's encapsulation efficiency was above 78.98%+/- 2.37%. The doripenem-loaded microparticle mean diameter ranged from 3.8 +/- 0.110 to 6.9 +/- 0.090m. Microparticles with 20% (w/w) L-leucine had the highest FPF ratio indicating the best aerosolization properties of the formulations. The efficacy of the formulations as an antibacterial agent was increased by forming doripenem-loaded microparticles compared to blank microparticles. P. aeruginosa showed the same susceptibility to all doripenem-loaded microparticle formulations. Cell viability of microparticles was between 70%+/- 0.08% and 90%+/- 0.04% at 0.5 and 10mg/mL concentration, respectively. Conclusions: Doripenem-loaded microparticles, produced using a combination of ionotropic gelation and spray-drying methods, are suitable for pulmonary drug delivery based on their particles size, zeta potential, cytotoxicity and high production yield. To our knowledge, this is the first study that microparticles containing doripenem were produced and characterized