-
[show abstract]
[hide abstract]
ABSTRACT: A bioanalytical method has been developed and validated for determination of drospirenone in human plasma. The analytical
method consists in the extraction of plasma sample with dichloromethane, followed by determination of drospirenone by LC–MS–MS
using levonorgestrel as internal standard. Separation was achieved on a Peerless cyano column with an isocratic mobile phase
consisting of methanol and ammonium formate buffer. Protonated ions formed by a Turboionspray in the positive mode were used
to detect analyte and IS. The MS–MS detection was by monitoring the fragmentation for drospirenone and for levonorgestrel
on a triple quadrupole mass spectrometer. The assay was calibrated over the range 5–100ngmL−1 with a correlation coefficient of 0.9998. Validation data showed intra-batch (n=6) CV%≤5.58 and RE (%) between −3.34 and +6.27 and inter-batch (n=18) CV%<6.08 and RE (%) between −1.84 and +6.73. Mean extraction recovery were 83.31–92.58% for three QC samples and
89.32% for IS. Plasma samples were stable for three freeze-thaw cycles, or 24h ambient storage, or 1 and 3months storage
at −20°C. Processed samples (ready for injection) were stable up to 72h at autosampler (4°C). This method has been used
for analyzing plasma samples from a bioequivalence study with 12 volunteers.
Chromatographia 04/2012; 68(9):713-720. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A simple liquid chromatographic method for the determination of gemifloxacin (CAS number 175463-14-6) in human plasma has
been developed. An aliquot quantity of 1mL plasma sample was taken and 0.1mL internal standard was added and mixed. 1mL
methanol was added to it. The mixture was then sonicated for 10min followed by 20min centrifugation at 5000rpm (g=3600). The supernatant layer was separated and filtered through simple filtration unit (membrane filter, 0.45μm) and injected
into the LC system consisting of Hypersil BDS, C18 (250×4.6mm, 5μm particle size) column, using 1% formic acid : methanol=65:35
(v/v) as mobile phase with ultra violet detection at 328nm. Lower limit of detection was 20ngmL−1 and lower limit of quantitation was 50ngmL−1. Maximum between-run precision was 14.614%. Mean extraction recovery was found to be 87.32 to 89.32%. Stability study showed
that after three freeze-thaw cycles the loss of three quality control samples were less than 10%. Samples were stable at room
temperature for 12h and at −20°C for 3months. Before injecting into LC system, the processed samples were stable for at
least 8h. The method was used to perform bioequivalence study in human volunteers.
Chromatographia 04/2012; 69(9):853-858. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A simple, precise and reproducible liquid chromatography–tandem mass spectrometry method has been developed and validated
according to the Food and Drug Administration guidelines for the simultaneous quantitation of antidiabetic drugs metformin,
glimiperide and pioglitazone in human plasma using glipizide as an internal standard. Quantitation was performed on a triple
quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring and positive
ion mode. Inter-batch and intra-batch coefficient of variation across four validation runs for the quality control samples
was less than 7%. The accuracy determined at quality control levels was within 92.81–105.13%. The method was applied to a
bioequivalence study.
Chromatographia 04/2012; 69(11):1243-1250. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was used to investigate the epileptogenic activity of gemifloxacin as a representative antibiotic with concentration-dependent antimicrobial activity. Rats received an intravenous infusion of gemifloxacin at a rate of 4 mg kg of body weight(-1) min(-1) over 50 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. An important delay was observed between concentrations of gemifloxacin in plasma and the EEG effect; this effect was accompanied by tremors and partial seizures. Indirect effect models failed to describe these data, which were successfully fitted by using an effect compartment model with a spline function to describe the relationship between effect and concentration at the effect site. The robustness of the PK-PD model was then assessed by keeping the dose constant but increasing the duration of infusion to 100 and 200 min. Although this was accompanied by PK modifications, PD parameters did not vary significantly, and the PK-PD model still applied. In conclusion, the successful PK-PD modeling of the gemifloxacin EEG effect in rats should be considered to predict and reduce the epileptogenic risk associated with this antibiotic as a representative fluoroquinolone.
Journal of Pharmaceutical Sciences 09/2009; 99(3):1535-47. · 3.06 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The following article from the Journal of Pharmaceutical Sciences, “Convulsant Activity and Pharmacokinetic–Pharmacodynamic Modeling of the Electroencephalogram Effect of Gemifloxacin in Rats,” by Bikash Roy, Anirbandeep Bose, Uttam Bhaumik, Ayan Das, Nilendra Chatterjee, Animesh Ghosh, Soumendra Darbar, Amlan Kanti Sarkar, Pinaki Sengupta, and T. K. Pal, published online on 7 August 2009 in Wiley InterScience and subsequently on Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal's Editor in Chief, Ronald T. Borchardt; Wiley Periodicals, Inc.; and the American Pharmacists Association. The retraction has been agreed due to the inappropriate use of previously published work.
Journal of Pharmaceutical Sciences 08/2009; 99(3):1535 - 1547. · 3.06 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A rapid, simple, sensitive and specific liquid chromatography–tandem mass spectrometry method was developed and validated
for simultaneous quantification of itopride hydrochloride and domperidone in human plasma. Both drugs were extracted by liquid–liquid
extraction with ethyl acetate and saturated borax solution. The chromatographic separation was performed on a reversed-phase
C18 column with a mobile phase of water–methanol (2:98, v/v) containing 0.5% formic acid. The protonated analyte was quantitated in positive ionization by multiple reaction monitoring
with a mass spectrometer. The assay exhibited linearity over the concentration range of 3.33–500ngmL−1 for itopride hydrochloride and 3.33–100ngmL−1 for domperidone in human plasma. The precursor to product ion transitions of m/z 359.1–72.3 and 426.0–147.2 were used to measure itopride hydrochloride and domperidone respectively. The method was found
suitable for the analysis of plasma samples collected during phase 1 pharmacokinetics study of itopride HCl 50mg and domperidone
20mg in 12 healthy volunteers after single oral doses of the combination drug.
Chromatographia 05/2009; 69(11):1-9. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A simple and feasible high-performance liquid chromatographic method with UV detection was developed and validated for the quantification of rimonabant in human plasma. The chromatographic separation was carried out in a Hypersil BDS, C(18) column (250 mm x 4.6mm; 5 microm). The mobile phase was a mixture of 10 mM phosphate buffer and acetonitrile (30:70, v/v) at a flow rate of 1.0 ml/min. The UV detection was set at 220 nm. The extraction recovery of rimonabant in plasma at three quality control (QC) samples was ranged from 84.17% to 92.64%. The calibration curve was linear for the concentration range of 20-400 ng/ml with the correlation coefficient (r(2)) above 0.9921. The method was specific and sensitive with the limit of quantification of 20 ng/ml. The accuracy and precision values obtained from six different sets of QC samples analyzed in separate occasions ranged from 88.13% to 106.48% and 0.13% to 3.61%, respectively. In stability tests, rimonabant in human plasma was stable during storage and assay procedure. The method is very simple, sensitive and economical and the assay was applied to human plasma samples in a clinical (pharmacokinetic) study of rimonabant.
Journal of pharmaceutical and biomedical analysis 03/2009; 49(4):1009-13. · 2.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An improved HPLC method was developed and validated for the determination of concentration of amisulpride (CAS 71675-85-9) in human plasma, an attempt to compare the bioavailability of two amisulpride tablet formulations (reference and test) containing 200 mg of amisulpride. Both the formulations were administered orally as a single dose, separated by washout period of 1 week. This HPLC method validated by examining the precision and accuracy for the inter-day and intra-day runs in a linear concentration range of 50-1200 ng/ml. Bioequivalence of two formulation were determined on 12 healthy Indian male volunteer in a single-dose, two-period, two-sequence, two-treatment crossover study. The content of amisulpride in plasma was determined by a validated HPLC method with UV detection. The formulations were compared using the parameters like area under the plasma concentration-time curve (AUC0-t), area under the plasma concentration-time curve from zero to infinity (AUC0-infinity), peak plasma concentration (Cmax), and time to reach peak plasma concentration (tmax). The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmic transformed AUC0-infinity and Cmax, values, between test and reference formulation. The 90% confidence interval for the ratio of the logarithmic transformed AUC0-t, AUC0-infinity, and Cmax were within the bioequivalence limit of 0.8-1.25 and the relative bioavailability of test formulation was 96.82% to that of reference formulation.
Arzneimittel-Forschung 01/2009; 59(4):166-70. · 0.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Defining a quantitative and reliable relationship between in vitro drug release and in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process. During the development of once daily extended-release (ER) tablet of glipizide, a predictive in vitro drug release method was designed and statistically evaluated using three formulations with varying release rates. In order to establish internally and externally validated level A in vitro-in vivo correlation (IVIVC), a total of three different ER formulations of glipizide were used to evaluate a linear IVIVC model based on the in vitro test method. For internal validation, a single-dose four-way cross over study (n=6) was performed using fast-, moderate-, and slow-releasing ER formulations and an immediate-release (IR) of glipizide as reference. In vitro release rate data were obtained for each formulation using the United States Pharmacopeia (USP) apparatus II, paddle stirrer at 50 and 100 rev. min(-1) in 0.1 M hydrochloric acid (HCl) and pH 6.8 phosphate buffer. The f(2) metric (similarity factor) was used to analyze the dissolution data. The formulations were compared using area under the plasma concentration-time curve, AUC(0-infinity), time to reach peak plasma concentration, T(max), and peak plasma concentration, C(max), while correlation was determined between in vitro release and in vivo absorption. A linear correlation model was developed using percent absorbed data versus percent dissolved from the three formulations. Predicted glipizide concentrations were obtained by convolution of the in vivo absorption rates. Prediction errors were estimated for C(max) and AUC(0-infinity) to determine the validity of the correlation. Apparatus II, pH 6.8 at 100 rev. min(-1) was found to be the most discriminating dissolution method. Linear regression analysis of the mean percentage of dose absorbed versus the mean percentage of in vitro release resulted in a significant correlation (r(2)>or=0.9) for the three formulations.
Biological & Pharmaceutical Bulletin 11/2008; 31(10):1946-51. · 1.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantification of ranolazine in human plasma. The analytical method consists in the precipitation of plasma sample with methanol, followed by the determination of ranolazine by an LC-MS/MS. The analyte was separated on a Peerless Cyano column (33 mm x 4.6 mm, 3 microm) an isocratic mobile phase of methanol-water containing formic acid (1.0%, v/v) (65:35, v/v) at a flow rate of 1.0 ml/min. Protonated ions formed by a turbo ionspray in positive mode were used to detect analyte and internal standard (IS). The MS/MS detection was made by monitoring the fragmentation of m/z 428.20-->279.50 for ranolazine and m/z 448.30-->285.20 for internal standard on a triple quadrupole mass spectrometer. The method was validated over the concentration range of 5-2000 ng/ml for ranolazine in human plasma with correlation coefficient of 0.9937 (S.D.: +/-0.00367, range: 0.9895-0.9963). The accuracy and precision values obtained from six different sets of quality control samples analyzed in separate occasions ranged from 94.53 to 117.86 and 0.14% to 4.56%, respectively. Mean extraction recovery was 82.36-94.25% for three quality control (QC) samples and 88.37% for IS. Plasma samples were stable for three freeze-thaw cycles, or 24h ambient storage, or 1 and 3 months storage at -20 degrees C. Processed samples (ready for injection) were stable up to 72 h at autosampler (4 degrees C). The developed method was successfully applied for analyzing ranolazine in plasma samples for a bioequivalence study with 12 healthy volunteers.
Journal of Pharmaceutical and Biomedical Analysis 10/2008; 48(5):1404-10. · 2.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study was to apply the simultaneous optimization method incorporating Artificial Neural Network (ANN) using Multi-layer Perceptron (MLP) model to the development of a metformin HCl 500 mg sustained release matrix tablets with an optimized in vitro release profile. The amounts of HPMC K15M and PVP K30 at three levels (-1, 0, +1) for each were selected as casual factors. In vitro dissolution time profiles at four different sampling times (1 h, 2 h, 4 h and 8 h) were chosen as output variables. 13 kinds of metformin matrix tablets were prepared according to a 2(3) factorial design (central composite) with five extra center points, and their dissolution tests were performed. Commercially available STATISTICA Neural Network software (Stat Soft, Inc., Tulsa, OK, U.S.A.) was used throughout the study. The training process of MLP was completed until a satisfactory value of root square mean (RSM) for the test data was obtained using feed forward back propagation method. The root mean square value for the trained network was 0.000097, which indicated that the optimal MLP model was reached. The optimal tablet formulation based on some predetermined release criteria predicted by MLP was 336 mg of HPMC K15M and 130 mg of PVP K30. Calculated difference (f(1) 2.19) and similarity (f(2) 89.79) factors indicated that there was no difference between predicted and experimentally observed drug release profiles for the optimal formulation. This work illustrates the potential for an artificial neural network with MLP, to assist in development of sustained release dosage forms.
CHEMICAL & PHARMACEUTICAL BULLETIN 03/2008; 56(2):150-5. · 1.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study presents the results of a two-way, two-period, two-treatment crossover investigation in 12 healthy Indian male subjects to assess the bioequivalence of two oral formulations containing 50 mg of diacerein (CAS 13739-02-1). Both formulations were administered orally as a single dose separated by a one-week washout period. The content of diacerein in plasma was determined by a validated HPLC method with UV detection. The formulations were compared using the parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)), peak plasma concentration (Cmax), and time to reach peak plasma concentration (tmax). The results of this study indicated that there were no statistically significant differences between the logarithmically transformed AUC(0-infinity) and Cmax, values of the two preparations. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limit of 0.8-1.25 and the relative bioavailability of the test formulation was 96.63% of that of the reference formulation. Thus, these findings clearly indicate that the two formulations are bioequivalent in terms of rate and extent of drug absorption.
Arzneimittel-Forschung 02/2008; 58(8):405-9. · 0.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This paper presents the results of a two-period, two-treatment, crossover study conducted in 12 Indian male volunteers under fasting conditions to assess the bioequivalence of two oral formulations (Reference and Test) containing 200 mg of faropenem (CAS 106560-14-9). Both of the formulations were administered orally as a single dose separated by a washout period of 1 week. The content of faropenem in plasma was determined by a validated HPLC method with UV detection. The formulations were compared using the parameters area under the plasma concentration-time curve (AUC0-t), area under the plasma concentration-time curve from zero to infinity (AUC0-infinity), peak plasma concentration (Cmax) and time to reach peak plasma concentration (tmax). The results Indicated that there were no statistically significant differences between the logarithmically transformed AUC0-infinity and Cmax values between the test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC0-t, AUC0-infinity and Cmax were within the bioequivalence limit of 0.8-1.25 and the relative bioavailability of the test formulation was 97.74% of that of the reference formulation.
Arzneimittel-Forschung 02/2008; 58(12):681-5. · 0.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A simple, rapid, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of metoprolol tartrate (MT) and ramipril, in human plasma. Both the drugs were extracted by liquid-liquid extraction with diethyl ether-dichloromethane (70:30, v/v). The chromatographic separation was performed on a reversed-phase C8 column with a mobile phase of 10 mM ammonium formate-methanol (3:97, v/v). The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The method was validated over the concentration range of 5-500 ng/ml for metoprolol and ramipril in human plasma. The precursor to product ion transitions of m/z 268.0-103.10 and m/z 417.20-117.20 were used to measure metoprolol and ramipril, respectively.
Journal of Chromatography B 11/2007; 858(1-2):13-21. · 2.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the current study was to design an oral sustained release matrix tablet of metformin HCl and to optimize the drug release profile using response surface methodology. Tablets were prepared by non-aqueous wet granulation method using HPMC K 15M as matrix forming polymer. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile. HPMC K 15M (X(1)) and PVP K 30 (X(2)) were taken as the independent variables. The dependent variables selected were % of drug released in 1 hr (rel(1 hr)), % of drug released in 8 hrs (rel(8 hrs)) and time to 50% drug release (t(50%)). Contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. The formulated tablets followed Higuchi drug release kinetics and diffusion was the dominant mechanism of drug release, resulting in regulated and complete release within 8 hrs. The polymer (HPMC K 15M) and binder (PVP K 30) had significant effect on the drug release from the tablets (p<0.05). Polynomial mathematical models, generated for various response variables using multiple linear regression analysis, were found to be statistically significant (p<0.05). Validation of optimization study, performed using 8 confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (+/-S.D.) 0.0437+/-0.3285. Besides unraveling the effect of the 2 factors on the in vitro drug release, the study helped in finding the optimum formulation with sustained drug release.
Yakugaku zasshi journal of the Pharmaceutical Society of Japan 08/2007; 127(8):1281-90. · 0.39 Impact Factor
