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.

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring.

Measurement of Purine Contents in Korean Alcoholic Beverages / 대한류마티스학회지

OBJECTIVE: Gout is one of the most common forms of inflammatory arthritides among men, which is caused primarily by chronic hyperuricemia. Although pharmacological therapy is the mainstay treatment to manage gout, limiting the consumption of dietary purine is also important. Several epidemiological studies have reported that alcohol consumption is closely related to hyperuricemia and gout. The objective of this study was to determine the purine content in common Korean alcoholic beverages using high performance liquid chromatography (HPLC) to provide a dietary guideline for those with hyperuricemia or gout. METHODS: Thirty-five alcoholic beverages were analyzed. Blindly labeled samples of each alcoholic beverage were degassed and frozen. The sample preparation prior to HPLC followed the methods of Japanese researchers. HPLC was performed to analyze adenine, guanine, hypoxanthine, and xanthine content in the alcoholic beverages. RESULTS: The standard curves were linear for all purines. Purine contents were as follows: beer (42.26~146.39 micromol/L, n=12), medicinal wine (8.2 and 40.41 micromol/L, n=2), rice wine (13.19 micromol/L), Makgeolri (11.71 and 24.72 micromol/L, n=2), red wine (0, 6.03, and 17.9 micromol/L, n=3). No purines were found in fruit wine (n=2), Kaoliang (n=1), white wine (n=1), or distilled alcoholic beverages, such as soju (n=10) or whiskey (n=1). CONCLUSION: Among popular Korean alcoholic beverages, beer contained a considerable amount of purines, whereas distilled alcoholic beverages did not. Patients with either gout or hyperuricemia should avoid alcoholic beverages, especially those containing large amounts of purines.

The Effect of Nutrition Education Program in Physical Health, Nutritional Status and Health-Related Quality of Life of the Elderly in Seoul

This study was performed to investigate the effects of nutrition education program in physical health, nutritional status and health-related quality of life (HRQoL )of the Elderly in Seoul. Nutrition education program was consisted of healthy eating, prevention and diet therapy of obesity, diabetes, cardiovascular disease, and osteoporosis. Seventy eight free-living elderly people (13 male, 65 female ), aged > or =60 years participated in this program. Before and after nutri-tion education program, we surveyed the general characteristics, physical health, general health, nutrition status, and health-related quality of life to the subjects. All the subjects were divided into program completers (N =47 )and non-completers (N =31 ). All the data were analyzed by student t-test, chi-square test, paired t-test, and marginal homo-geneity test using SPSS 9.0 version at p <0.05. After nutrition education program, physical activity and ADL maintained, however IADL improved in program noncompleters. In eating habits, 'slow eating' significantly improved in program completers in program completers. Nutrition knowledge and recognition scores were significantly increased in both groups, and accuracy score was significantly increased in program completers. However, nutrient-intakes of %RDA were not significantly changed in both groups, and it seemed to be more influenced by other factors such as 'family income' or 'family type' than by the nutrition education program. In HRQoL, social functioning was improved after nutrition education program in both groups (p <0.05 ). The nutrition education program has more effects on the pro-gram completers than on the noncompleters, and it is also needed social supports for the Elderly to fulfill their nutrient requirements.