A simple and rapid 3D view method for selective and sensitive determination of paclitaxel in micro volume rat plasma by LC-diode array UV and its application to a pharmacokinetic study

A simple, highly repeatable and reproducible method for the estimation of Paclitaxel (TAX) in micro volume amounts of rat plasma is successfully developed and validated. The extraction procedure using 800 μL of ice-cold acetonitrile is very simple and economical with high sensitivity. The rectangular ratiograms and purity curve demonstrate the selectivity of the method. The validation and stability results show that propylparaben (PP) is a suitable internal standard (resolution 7.70 ± 0.15 min) for the estimation of TAX in micro volume rat plasma. TAX and PP are separated by isocratic reversed-phase high-performance liquid chromatography with diode array UV method with a retention time of 8.0 ± 0.25 and 5.3 ± 0.15 min, respectively, with a total run time of 10 min. The system suitability results show that the method has good reproducibility. The stability of TAX is well studied in rat plasma, and the % RSD of all stability studies of TAX are well within the acceptable range of ± 20 % at the lower limit of quantitation (LLOQ) and ± 15% at all quality control levels. The limit of detection (LOD) and LLOQ of the method are 5 and 10 ng/mL, respectively. This rapid method is successfully used to study the i.v pharmacokinetic of TAX at 10 mg/kg in wistar rats, and drug concentration is detected up to 24 h.     

Development and Validation of an Stability Indicating RP-LC Method for Determination of Imatinib Mesylate

A new, sensitive and stability indicating liquid chromatographic method has been developed for the determination of imatinib mesylate (IM). Efficient chromatographic separation was achieved using a C₁₈ column with simple mobile phase combination delivered in an isocratic mode and quantitation was carried out using ultraviolet detection. For the first time, a novel microwave assisted degradation procedure was employed for stress testing studies. In addition, orthogonal separation technique was applied to demonstrate selectivity of the proposed method. The method has demonstrated excellent linearity over the range of 25–1,600 ng mL⁻¹. Moreover, the method was found to be sensitive with a low limit of detection (3.35 ng mL⁻¹) and limit of quantitation (10.16 ng mL⁻¹). The method has shown good and consistent recoveries (99.35–100.69%) with low intra- and inter-day relative standard deviation (RSD) (<2.5%). Experimental design confirmed that peak area was unaffected by small changes in critical factors, in robustness study. The validated method was successfully applied for determination of IM in pharmaceutical formulations.

     

Development and validation of an ion-pairing RP-HPLC method for the estimation of gatifloxacin in bulk and formulations

A new, simple, and sensitive ion-pair reverse-phase liquid chromatographic method is developed and validated for the estimation of 1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (gatifloxacin) in bulk and formulations using a UV detector under isocratic conditions. The selected mobile phase consists of the aqueous phase (a 25 mM citrate buffer comprising of 10mM cationic and anionic pairing agents, pH adjusted to 3.5) and acetonitrile (52:48%, v/v). The selected wavelength is 292 nm. Retention time of gatifloxacin is 5.2 min. The linearity range is found to be 50 to 1000 ng/mL (the regression equation is area = 105.5 x concentration in ng/mL--695.8), and the regression coefficient is 0.9996. Validation results demonstrate accuracy, precision, and reproducibility (relative standard deviation < 3%) of the method. The detection and quantitation limits are found to be 6.50 and 17.38 ng/mL, respectively. The method is successfully used for the estimation of gatifloxacin in a variety of dosage forms, and the results are in good agreement with the label claims.     

Design and in vitro evaluation of zidovudine oral controlled release tablets prepared using hydroxypropyl methylcellulose

Oral controlled release matrix tablets of zidovudine were prepared using different proportions and different viscosity grades of hydroxypropyl methylcellulose. The effect of various formulation factors like polymer proportion, polymer viscosity and compression force on the in vitro release of drug were studied. In vitro release studies were carried out using United States Pharmacopeia (USP) type 1 apparatus (basket method) in 900 ml of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using Zero-order model equation, Higuchi's square-root equation and Ritger-Peppas' empirical equation. Compatibility of drug with various formulations excipients used was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 10% hydroxypropyl methylcellulose (HPMC) 4000 cps were found to show a good initial drug release of 21% in the first hour and extended the release upto 16 h. Matrix tablets containing 20% HPMC 4000 cps and 10% HPMC 15000 cps showed a first hour release of 18% and extended the release upto 20 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of zidovudine, with good initial release (17-25% in first hour) and which extend the release upto 16-20 h, can overcome the disadvantages of conventional tablets of zidovudine.     

Stability indicating liquid chromatographic method for simultaneous quantification of betamethasone valerate and tazarotene in in vitro and ex vivo studies of complex nanoformulation

Low‐potency corticosteroid betamethasone valerate and vitamin‐A tazarotene are used in combination for effective treatment of psoriasis. There is no robust high‐performance liquid chromatography analytical technique available for simultaneous estimation of betamethasone valerate and tazarotene in conventional and nanocarriers based formulations. A simple, accurate, robust isocratic high‐performance liquid chromatography method was developed for simultaneous estimation of betamethasone valerate and tazarotene in topical pharmaceutical formulations. The developed method was validated as per the regulatory guidelines. The validated method was linear over the concentration range of 150–6000 ng/mL (r² > 0.999) at 239 nm wavelength. Limits of detection and quantification of two analytes were 50 and 150 ng/mL, respectively. The %relative standard deviation for intraday and interday precision was less than 2%. The method was also evaluated in the presence of forced degradation conditions. The developed method was successfully applied for in vitro and ex vivo drug release studies of in‐house designed nanoformulations.     

Development and Validation of an Stability Indicating RP-LC Method for Determination of Imatinib Mesylate

A new, sensitive and stability indicating liquid chromatographic method has been developed for the determination of imatinib mesylate (IM). Efficient chromatographic separation was achieved using a C₁₈ column with simple mobile phase combination delivered in an isocratic mode and quantitation was carried out using ultraviolet detection. For the first time, a novel microwave assisted degradation procedure was employed for stress testing studies. In addition, orthogonal separation technique was applied to demonstrate selectivity of the proposed method. The method has demonstrated excellent linearity over the range of 25–1,600 ng mL^?1. Moreover, the method was found to be sensitive with a low limit of detection (3.35 ng mL^?1) and limit of quantitation (10.16 ng mL^?1). The method has shown good and consistent recoveries (99.35–100.69%) with low intra- and inter-day relative standard deviation (RSD) (<2.5%). Experimental design confirmed that peak area was unaffected by small changes in critical factors, in robustness study. The validated method was successfully applied for determination of IM in pharmaceutical formulations.