Development of a LC-MS/MS for Quantification of Venlafaxine in Human Plasma and Application to Bioequivalence Study in healthy Korean Subjects

A simple, rapid and selective liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is developed and validated for quantification of venlafaxine in human plasma with simple liquid-liquid extraction step consisted of extraction with ether and dichloromethane for 10 min and mixing with 1 M sodium acetate in human plasma using fluoxetine as an internal standard (IS). The analyte are separated using an isocratic mobile phase consisted of acetonitrile and 5 mM ammonium formate (4/3, v/v) on a isocratic YMC hydrosphere C18 (2.0x50.0 mm, 3.0 microm) column and analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using the transitions of respective [M+H](+) ions, m/z 278.2-->260.3 and m/z 310.1-->148.1 for quantification of venlafaxine and IS, respectively. The standard calibration curves showed good linearity within the range of 1.0-200.0 ng/mL (r2=0.9986, 1/chi2 weighting). The lower limit of quantification (LLOQ) was 1.0 ng/mL. The retention times of venlafaxine and IS were 0.6 min and 0.7 min that means the potential for the high-throughput potential of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. Acceptable precision and accuracy were obtained for the concentrations over the standard curve range. The validated method was successfully applied to bioequivalence study after 75-mg of venlafaxine sustained-release (SR) capsule in 24 healthy Korean subjects.

Safety and Effectiveness of Long Acting Injectable Antipsychotic Paliperidone Palmitate Treatment in Schizophrenics : A 24-Week Open-Label Study

OBJECTIVES: We investigated the effectiveness and safety when treated in schizophrenics with paliperidone palmitate, a long acting injectable antipsychotic. METHODS: This was a 24-week open-label study, performed at one center in Korea. The eligible patients with schizophrenia diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were enrolled. Patients received long-acting paliperidone palmitate injection (234 mg, baseline; 156 mg, week 1 ; then once 4 weeks flexible dosing). Effectiveness assessments were measured by the Positive and Negative Syndrome Scale (PANSS), The Clinical Global Impression Severity Scale (CGI-S), The Personal and Social Performance (PSP) at baseline, week 1, every 4 weeks untill 24 weeks or endpoint. Safety assessments were measured by The Extrapyramidal Symptom Rating Scale (ESRS), body weight (BW) and incidence of adverse events. Oral antipsychotics were stopped or tapered off within next 14 days. RESULTS: Of 20 patients recruited, 9 patients (45%) completed the study. Paliperidone palmitate produced a significant improvement in PANSS total score from baseline to endpoint. The response rate was 75% [mean change (+/- SD) -25.9 +/- 14.4, all p or = 10%) in paliperidone palmitate were anticholinergic adverse event, extrapyramidal symptoms, weight gain, akathisia, insomnia, headache, agitation, anxiety and GI trouble. ESRS score is not statistically significant, but tends to get better at the end of the study when compared to baseline. CONCLUSIONS: Our study results demonstrated maintained effectiveness and safety of paliperidone palmitate treatment in schizophrenics. And provides both clinicians and patients with a new choice of treatment that can improve the outcome of long term therapy. Their potential effectiveness and safety should be better addressed by future randomized-controlled trials.

Effect of Ginkgo Biloba Extract on the Survival of Cultured Human Trabecular Meshwork Cells

PURPOSE: To investigate the effect of Ginkgo biloba extract (GBE, EGb-761) on the survival of cultured human trabecular meshwork cells (HTMC). METHODS: Free radical scavenging activity of GBE was assessed with a DPPH assay. Primarily cultured HTMC were exposed to 10 and 100 microgram/ml of GBE. 0.3 mM sodium cyanide and 100 micrometer hydrogen peroxide were added to the culture medium with GBE for 48 hr. Cellular survival and nitrite production were assessed by MTT assay and Griess assay, respectively. RESULTS: GBE showed free radical scavenging activity. GBE increased the cellular survival of HTMC significantly in a dose-dependent manner under hypoxia or serum-deprived condition, but not to hydrogen peroxide. GBE increased nitric oxide production but not to statistically significant levels. CONCLUSIONS: GBE promotes proliferation and has cytoprotective effects in the context of HTMC exposed to serum-deprived or hypoxic conditions. However oxidative stress induced by hydrogen peroxide did not have an effect on proliferation of HTMC. In addition these effects were not related to the production of nitric oxide.

Effect of Ginkgo Biloba Extract on the Proliferation of Cultured Human Tenon Capsule Fibroblasts

PURPOSE: To investigate the effect of Ginkgo biloba extract (GBE) on the proliferation of cultured human Tenon capsule fibroblasts (HTCF). METHODS: Free radical scavenging activity of GBE was assessed with a DPPH assay. Primarily cultured HTCF were exposed to 10 and 100 microgram/ml of GBE, and the effect of this extract on HTCF survival was assessed. Following 48 hr exposure to the media with or without serum, cellular survival and nitrite production were assessed by MTT and Griess assays. To evaluate whether GBE had a cytoproptective effect, HTCF were cultured in a combination of GBE and either sodium cyanide or hydrogen peroxide. RESULTS: GBE showed free radical scavenging activity. GBE increased the cellular survival of HTCF significantly in a dose-dependent manner and provided a cytoprotective effect when cells were exposed to sodium cyanide or were deprived of serum, but not when hydrogen peroxide was added to the medium. GBE decreased nitric oxide production but not to a statistically degree. CONCLUSIONS: GBE promotes proliferation of HTCF and has a cytoprotective effect in serum-deprived or hypoxic conditions. This suggests that GBE may be involved in the regulation of conjunctival wound healing by increasing the survival of HTCF.