The Experts below are selected from a list of 525 Experts worldwide ranked by ideXlab platform
Yong-bok Lee - One of the best experts on this subject based on the ideXlab platform.
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Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of Levosulpiride in healthy subjects
Neuroscience, 2010Co-Authors: Hea-young Cho, Hee-doo Yoo, Yong-bok LeeAbstract:The purposes of this study were to clarify the involvement of P-glycoprotein in the absorption of Levosulpiride in knockout mice that lack the Abcb1a/ 1b gene, and to evaluate the relationship between genetic polymorphisms in ABCB1 (exon 12, 21 and 26) and Levosulpiride disposition in healthy subjects. The plasma and brain samples were obtained after oral administration (10 μg/g) of Levosulpiride to abcb1a/1b(−/−) and wild-type mice (n=3∼6 at each time point). The average brain-to-plasma concentration ratio and blood-brain barrier partitioning of Levosulpiride were 2.3- and 2.0-fold higher in Abcb1a/1b(−/−) mice than in wild-type mice, respectively. A total of 58 healthy Korean volunteers receiving a single oral dose of 25 mg Levosulpiride participated in this study. The subjects were evaluated for polymorphisms of the ABCB1 exon 12 C1236T, exon 21 G2677A/T (Ala893Ser/Thr) and exon 26 C3435T using polymerase chain reaction restriction fragment length polymorphism. The PK parameters (AUC0–4h, AUC0–∞ and Cmax.) of ABCB1 2677TT and 3435TT subjects were significantly higher than those of subjects with at least one wild-type allele (P A/T in exon 21 and 3435C>T in exon 26 of ABCB1 on Levosulpiride disposition.
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Pharmacokinetic Characteristics of Levosulpiride in Relation to the Genetic Polymorphism of MDR1: From Knockout Mouse to Human
Journal of Korean Pharmaceutical Sciences, 2007Co-Authors: Hea-young Cho, Yong-bok LeeAbstract:The purposes of this study were to clarify the involvement of P-glycoprotein (P-gp) in the efflux of Levosulpiride in knockout mice that lack the mdr1a1b gene and to evaluate the relationship between the genetic polymorphisms in MDR1 gene (exon 21) and Levosulpiride disposition in healthy Korean subjects. After oral administration () of Levosulpiride to mdr1a/1b(-/-) and wild-type mice, plasma and brain samples were obtained at 45 min. We also investigated the genotype for MDR1 (exon 21) gene in humans using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A single oral dose of 25 mg Levosulpiride was administered to 58 healthy subjects, who were based on the MDR1 genotype for the G2677T SNP. Blood samples were taken up to 36 hr after dosing. The concentrations of Levosulpiride in mouse plasma and brain were statistically significant difference between the two animal groups (P, partial AUC () and were significantly different between homozygous 2677TT subjects and the subjects with at least one wild-type allele (GG and GT subjects, P=0.012 for ; P=0.008 for ; P=0.038 for ). The results confirm that Levosulpiride is a P-gp substrate in vivo, and clearly demonstrate the effect of SNP 2677G>T in exon 21 of the MDR1 gene on Levosulpiride disposition.
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Hydrophilic interaction liquid chromatography–tandem mass spectrometry for the determination of Levosulpiride in human plasma
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2004Co-Authors: In Bok Paek, Yong-bok Lee, Ya Moon, Hui-hyun Kim, Hye Won Lee, Hye Suk LeeAbstract:A rapid, sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric (HILIC-MS/MS) method for the determination of Levosulpiride in human plasma was developed. Levosulpiride and internal standard, tiapride were extracted from human plasma with ethyl acetate at pH 11 and analyzed on an Atlantis HILIC silica column with the mobile phase of acetonitrile-ammonium formate (190 mM, pH 3.0) (94:6, v/v). The analytes were detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.999) over the concentration range of 1.00-200 ng/ml. The lower limit of quantification for Levosulpiride was 1.00 ng/ml using 100 microl plasma sample. The coefficient of variation and relative error for intra- and inter-assay at three quality control (QC) levels were 3.8-9.1 and -2.9 to -0.1%, respectively. The recoveries of Levosulpiride ranged from 80.5 to 87.4%, with that of tiapride (internal standard) being 84.6%. This method was successfully applied to the pharmacokinetic study of Levosulpiride in humans.
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hydrophilic interaction liquid chromatography tandem mass spectrometry for the determination of Levosulpiride in human plasma
Journal of Chromatography B, 2004Co-Authors: In Bok Paek, Yong-bok Lee, Ya Moon, Hui-hyun Kim, Hye Won Lee, Hye Suk LeeAbstract:A rapid, sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric (HILIC-MS/MS) method for the determination of Levosulpiride in human plasma was developed. Levosulpiride and internal standard, tiapride were extracted from human plasma with ethyl acetate at pH 11 and analyzed on an Atlantis HILIC silica column with the mobile phase of acetonitrile-ammonium formate (190 mM, pH 3.0) (94:6, v/v). The analytes were detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.999) over the concentration range of 1.00-200 ng/ml. The lower limit of quantification for Levosulpiride was 1.00 ng/ml using 100 microl plasma sample. The coefficient of variation and relative error for intra- and inter-assay at three quality control (QC) levels were 3.8-9.1 and -2.9 to -0.1%, respectively. The recoveries of Levosulpiride ranged from 80.5 to 87.4%, with that of tiapride (internal standard) being 84.6%. This method was successfully applied to the pharmacokinetic study of Levosulpiride in humans.
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Pharmacokinetics and bioequivalence evaluation of 2 Levosulpiride preparations after a single oral dose in healthy male Korean volunteers.
International journal of clinical pharmacology and therapeutics, 2004Co-Authors: H Y Cho, Yong-bok LeeAbstract:Objective: To evaluate the bioequivalence of a single oral 25 mg dose of 2 Levosulpiride preparations in healthy male Korean volunteers. Subjects, materials and methods: The study was conducted as a randomized, 2-period crossover design in 28 healthy male Korean volunteers who received a single oral dose of 25 mg Levosulpiride tablet in each study period. There was a 6-day washout period between the doses. Serum concentrations of Levosulpiride up to 36 hours after the administration were determined using a validated HPLC method with fluorescence detection. In addition, in vitro dissolution profiles of both preparations were examined. The pharmacokinetic parameters such as AUC 0 - t (the area under the curve from zero to the time), AUC 0 - ∞ (the area under the curve from zero to infinity), C m a x (maximum serum concentration), t m a x (time to reach C m a x ) and t 1 / 2 (terminal half-life) were analyzed by non-compartmental analysis, and the analysis of variance (ANOVA) was carried out using logarithmically transformed AUC 0 - t , AUC 0 - ∞ and C m a x , and untransformed T m a x . Results: In vitro dissolution profiles were similar by calculating similarity factor (f 2 = 67.73). There were no significant differences between the 2 preparations in AUC 0 - t , AUC 0 - ∞ and C m a x . The point estimates (90% confidence intervals) for AUC 0 - t , AUC 0 - ∞ and C m a x were 1.085 (1.003-1.173), 1.069 (0.991 - 1.153) and 1.075 (0.954 to 1.210), respectively, satisfying the bioequivalence criteria of 0.80 - 1.25 as proposed by the US FDA and the Korean legislation. No statistically significant difference was found for t m a x and t 1 / 2 values. Conclusion: From the results of the present study, it is indicated that the 2 preparations of Levosulpiride are bioequivalent and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice.
C Sasikala - One of the best experts on this subject based on the ideXlab platform.
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development of uv spectrophotometry and rp hplc methods for the estimation of Levosulpiride in bulk and in tablet formulation
Asian Journal of Research in Chemistry, 2010Co-Authors: S P Silambarasan, K Anandakumar, R Venkatalakshmi, C SasikalaAbstract:Two new simple, sensitive, rapid, accurate and precise methods, namely UV spectrophotometric and RP-HPLC methods were developed for the estimation of Levosulpiride in bulk and in tablet formulation. In UV spectrophotometric method, Levosulpiride exhibited maximum absorbance at 291.5 nm with apparent molar absorptivity of 2.6031 x 103 L mol−1 cm −1 in 0.1M HCl. Beer's law was obeyed in the concentration range of 10 -50 μg/ml. In RP-HPLC method, the elution was done using a mobile phase consisting of methanol and 25 mM phosphate buffer pH 3.5 (pH adjusted with phosphoric acid, 15:85 v/v) on Shimadzu HPLC C18 (4.6 x 150 mm) column at a flow rate of 0.8 ml/min with UV detection at 293 nm. An external standard calibration method was employed for quantization. The elution time was 5.08 minutes. Beer's law was found to be obeyed in the concentration range of 4 – 24 μg/ml. The results of proposed methods were validated statistically and by recovery studies. The % RSD values for recovery studies were found to be less than 2% for the both methods. Hence the proposed methods were successfully used to determine the drug content in bulk and in tablet formulation.
Dinesh O. Shah - One of the best experts on this subject based on the ideXlab platform.
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Development and Validation of Derivative Spectrophotometric Method for Simultaneous Estimation of Levosulpiride and Esomeprazole in Capsule Dosage Form
Asian Journal of Research in Chemistry, 2013Co-Authors: Brijen Vaghela, Gunjansinh Parmar, Shailesh A. Shah, Dinesh O. ShahAbstract:The use of first order derivative spectrophotometry allows simultaneous determination of Levosulpiride and esomeprazole in fixed dose combination products. The wavelengths 275 nm and 291.5 nm of first derivative spectrum were selected for the estimation of Levosulpiride and esomeprazole, respectively without mutual interference. The method was linear in the concentration range 25–125 μg/ml and 5–25 μg/ml for Levosulpiride and esomeprazole, respectively. The method was validated in terms of accuracy and precision. The result of the formulation analysis shows that the proposed method can be successfully used for the simultaneous estimation of both the drugs in their combined capsule dosage form.
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Development and Validation of Derivative Spectrophotometric Method for Simultaneous Estimation of Levosulpiride and Pantoprazole in Capsule Dosage Form
Asian Journal of Research in Chemistry, 2012Co-Authors: Gunjansinh Parmar, Shailesh A. Shah, Khushbu Naik, Renu Chauhan, Dinesh O. ShahAbstract:The use of first order derivative spectrophotometry allows simultaneous determination of Levosulpiride and pantoprazole in fixed dose combination products. The wavelengths 252.5 nm and 291.0 nm of first derivative spectrum were selected for the estimation of Levosulpiride and pantoprazole, respectively without mutual interference. The method was linear in the concentration range 25–125 μg/ml and 5–25 μg/ml for Levosulpiride and pantoprazole, respectively. Validation studies confirmed the accuracy and precision of the proposed method. The result of the formulation analysis shows that the proposed method can be successfully used for the simultaneous estimation of both the drugs in their combined capsule dosage form.
S P Silambarasan - One of the best experts on this subject based on the ideXlab platform.
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development of uv spectrophotometry and rp hplc methods for the estimation of Levosulpiride in bulk and in tablet formulation
Asian Journal of Research in Chemistry, 2010Co-Authors: S P Silambarasan, K Anandakumar, R Venkatalakshmi, C SasikalaAbstract:Two new simple, sensitive, rapid, accurate and precise methods, namely UV spectrophotometric and RP-HPLC methods were developed for the estimation of Levosulpiride in bulk and in tablet formulation. In UV spectrophotometric method, Levosulpiride exhibited maximum absorbance at 291.5 nm with apparent molar absorptivity of 2.6031 x 103 L mol−1 cm −1 in 0.1M HCl. Beer's law was obeyed in the concentration range of 10 -50 μg/ml. In RP-HPLC method, the elution was done using a mobile phase consisting of methanol and 25 mM phosphate buffer pH 3.5 (pH adjusted with phosphoric acid, 15:85 v/v) on Shimadzu HPLC C18 (4.6 x 150 mm) column at a flow rate of 0.8 ml/min with UV detection at 293 nm. An external standard calibration method was employed for quantization. The elution time was 5.08 minutes. Beer's law was found to be obeyed in the concentration range of 4 – 24 μg/ml. The results of proposed methods were validated statistically and by recovery studies. The % RSD values for recovery studies were found to be less than 2% for the both methods. Hence the proposed methods were successfully used to determine the drug content in bulk and in tablet formulation.
Young-ran Yoon - One of the best experts on this subject based on the ideXlab platform.
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Liquid chromatography–tandem mass spectrometry quantification of Levosulpiride in human plasma and its application to bioequivalence study
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2010Co-Authors: Prasad Phapale, Hae Won Lee, Mi-sun Lim, Sook Jin Seong, Eun-hee Kim, Jeonghyeon Park, Miran Lee, Sung-kyu Hwang, Young-ran YoonAbstract:An improved method for determining levels of Levosulpiride in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated. The protein precipitation method was used for plasma sample preparation. Levosulpiride and an internal standard (IS) were isocratically separated on a UPLC BEH C(18) column with a mobile phase of ammonium formate buffer (1mM, adjusted to pH 3 with formic acid) and acetonitrile (60:40, v/v). MS/MS detection was performed by monitoring the parent-->daughter pair of Levosulpiride and the IS at m/z 342-->112 and 329-->256, respectively. The method was linear from 2.5 to 200ng/mL and exhibited acceptable precision and percent recovery. The method was successfully demonstrated in pharmacokinetic and bioequivalence studies of two Levosulpiride oral formulations administered to healthy volunteers. When compared to the previous LC-MS methods, the proposed method is faster, well-validated, and uses lesser plasma volume and a similar sensitivity. The use of UPLC allowed rapid and sensitive quantification of Levosulpiride, making this method suitable for high-throughput clinical applications.