Pharmacokinetics, safety, and bioequivalence of apixaban tablets in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs). RESULTS: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs). CONCLUSION: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.

Ultrasensitive analysis of glucose in serum by capillary electrophoresis with LIF detection in combination with signal amplification strategies and on-column enzymatic assay.

A highly specific and sensitive method for glucose quantification in human serum samples based on on-column enzymatic assay is described. In this method, the head of the capillary was used as a nanoliter-microreactor, the diluted samples spiked with a novel fluorogenic reagent named 2-[6-(4'-amino) phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF), and the mixed enzyme solutions of glucose oxidase (GOx) and horseradish peroxidase (HRP), were individually injected into the capillary. Hydrogen peroxide (H2 O2 ) generated in situ by catalytic reaction between GOx and glucose, activates APF in the presence of HRP to form a highly fluorescent product, which was electrophoretically separated from the unreacted APF and detected by the LIF detector. The proposed method allowed the determination of glucose down to 10 nM in real samples, with RSD values lower than 3.5%, which also has the potential for measurements of multicomponents in many other systems including measurement of α-glucosidase activity and screening for its inhibitors.

Simultaneous determination of pharmacologically active ingredients in Rhodiola by capillary chromatography with electrochemical detection.

Rhodiola, in which there are abundant pharmacologically active ingredients, is one of the functional adaptogenic agent that aid specific bodily functions to adapt to the changes and stress of life in addition to being tonic. In an attempt to qualitatively and quantitatively determine the pharmacologically active ingredients in Rhodiola, a new method based on capillary electrophoresis with electrochemical detection (CE-ED) has been developed. The effects of working electrode potential, pH and concentration of running buffer, separation voltage, applied potential and injection time on CE-ED were investigated. Under the optimum conditions, the analytes could be well separated within 24 min at the separation voltage of 18 kV in a 80 mmol L(-1) borax running buffer (pH 9.0). Good linear relationship was established between peak current and concentration of analytes over two orders of magnitude with detection limits (S/N=3) ranged from 3.16 x 10(-7) to 1.11 x 10(-7)g mL(-1) for all target ingredients. This proposed method has been successfully applied for the analysis of real samples, with satisfactory results.

Determination of pharmacologically active ingredients in sweet potato (Ipomoea batatas L.) by capillary electrophoresis with electrochemical detection.

Sweet potato (Ipomoea batatas L.), in which vitamin C, chlorogenic acid, caffeic acid, quercetin, and rutin are abundant, is one of the functional food products aimed at introducing human dietary ingredients that aid specific body functions in addition to being nutritious. A method based on capillary electrophoresis with electrochemical detection (CE-ED) to qualitatively and quantitatively determine the pharmacologically active ingredients in sweet potato has been developed by our group. The effects of working electrode potential, pH and concentration of running buffer, separation voltage, applied potential, and injection time on CE-ED were investigated. Under the optimum conditions, the analytes could be well-separated within 20 min at the separation voltage of 18 kV in a 60 mmol L(-1) Borax running buffer (pH 9.0). A good linear relationship was established between peak current and concentration of analytes over 2 orders of magnitude with detection limits (S/N = 3) ranging from 7.14 x 10(-7) to 2.88 x 10(-7) g mL(-1) for all target ingredients. The satisfactory results show that this method is very successful and effective for the analysis of real samples.

[Determination of bioactive components in Semencustae by capillary electrophoresis with electrochemical detection].

A method of high performance capillary electrophoresis with electrochemical detection (CE-ECD) has been developed for the determination of five bioactive components in Semencustae, namely rutin, hyperoside, kaempferol, p-coumaric acid and quercetin. The effects of several factors such as the acidity and concentration of the running buffer, the separation voltage, the applied potential and the injection time on CE-ECD were investigated. Under the optimized conditions, these five components can be separated in a 50.0 mmol/L borax running buffer (pH 9.0) within 19 minutes. A 300 microm diameter carbon disk electrode was used as the working electrode positioned carefully opposite to the outlet of the capillary in a wall-jet configuration at potential of + 950 mV (vs. saturated calomel electrode as reference electrode, SCE). Good linear relationships were established between the peak current and concentration of analytes over two orders of magnitude. The detection limits (S/N = 3) were 1.93 x 10(-5), 3.55 x 10(-4), 3.65 x 10(-5), 1. 73 x 10(-5) and 1.46 x 10(-4) g/L for rutin, hyperoside, kaempferol, p-coumaric acid and quercetin, respectively. The method has been successfully applied to the determination of these analytes in Semencustae samples after a relatively simple extraction procedure, and the assay results were satisfactory.

Determination of antioxidants in cosmetics by micellar electrokinetic capillary chromatography with electrochemical detection.

A new and efficient method for the determination of antioxidants [Propyl gallate (PG), tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT)] in cosmetics has been established by using micellar electrokinetic capillary chromatography with electrochemical detection (MECC-ED). Under the optimum conditions of the method, all analytes were successfully separated within 13 min at the separation voltage of 18 kV in a 20 mmol/L borate running buffer (pH 7.4) containing 25 mmol/L sodium dodecyl sulfate. The excellent linearity was obtained in the concentration range from 5.0 x 10(-4) to 2.0 x 10(-6) mol/L and the detection limits (S/N = 3) of PG, TBHQ, BHA, and BHT range from 3 x 10(-7) to 3 x 10(-6) mol/L.

Determination of uric acid and p-aminohippuric acid in human saliva and urine using capillary electrophoresis with electrochemical detection: potential application in fast diagnosis of renal disease.

The monitoring of uric acid (UA) and p-aminohippuric acid (PAH) levels in biological samples is routinely carried out in clinical laboratories as an indication of renal disease. With the aim of investigation of the correlation between the trace amounts of UA and PAH in human saliva or urine and renal diseases, we carried out the determination of UA and PAH in human saliva and urine by using capillary electrophoresis with electrochemical detection (CE-ED) in this work. Under the optimum conditions, UA, PAH and three coexisting analytes could be well separated within 21 min at the separation voltage of 14 kV in 80 mmol/L borax running buffer (pH 9.2). Good linear relationship was established between peak current and concentration of analytes over two orders of magnitude with detection limits (S/N = 3) ranged from 5.01 x 10(-7) to 2.00 x 10(-6) mol/L for all analytes. The result shows that this proposed method could be successfully applied for the study on the correlation between the levels of UA and PAH in human saliva and urine and renal diseases, and provide an alternative and convenient method for the fast diagnosis of renal disease.

Fast determination of sugars in Coke and Diet Coke by miniaturized capillary electrophoresis with amperometric detection.

The fast separation capability of a novel miniaturized capillary electrophoresis with amperometric detection (CE-AD) system was demonstrated by determining sugar contents in Coke and diet Coke with an estimated separation efficiency of 60,000 TP/m. Factors influencing the separation and detection processes were examined and optimized. The end-capillary 300 microm Cu wire amperometric detector offers favorable signal-to-noise characteristics at a relatively low potential (+0.50 V vs. Ag/AgCl) for detecting sugars. Three sugars (sucrose, glucose, and fructose) have been separated within 330 s in a 8.5 cm length capillary at a separation voltage of 1000 V using a 50 mM NaOH running buffer (pH 12.7). Highly linear response is obtained for the above compounds over the range of 5.0 to 2.0 x 10(2) microg/mL with low detection limit, down to 0.8 microg/mL for glucose (S/N = 3). The injection-to-injection repeatability for analytes in peak current (RSD < 3.6%) and for migration times (RSD < 1.4%) was excellent. The new miniaturized CE-AD system should find a wide range of analytical applications involving assays of carbohydrates as an alternative to conventional CE and micro-CE.

Determination and differentiation of Flos Chrysanthemum based on characteristic electrochemical profiles by capillary electrophoresis with electrochemical detection.

A high-performance capillary electrophoresis with electrochemical detection (CE-ED) method has been developed for the analysis of bioactive ingredients in Flos Chrysanthemum in this work. The effects of several factors such as the acidity and concentration of running buffer, the separation voltage, the applied potential, and the injection time were investigated. Under the optimum conditions, the eight analytes could be well separated within 20 min at the separation voltage of 14 kV in a 50 mmol/L Borax running buffer (pH 9.2). A 300 microm diameter carbon disk electrode has a good response at a potential of +950 mV (vs SCE) for all analytes. Good linear relationship was established over 3 orders of magnitude with detection limits (S/N = 3) that ranged from 1.9 x 10(-7) to 3.0 x 10(-8) g/mL. This proposed method has been successfully applied for the determination and differentiation of six kinds of popular Flos Chrysanthemum samples based on their characteristic electrochemical profiles, and the results are satisfactory.

Determination of uric acid in human saliva by capillary electrophoresis with electrochemical detection: potential application in fast diagnosis of gout.

The clinical manifestations of gout result from the formation and deposition of uric acid (UA) crystals. The monitoring of UA level in less invasive biological samples such as saliva is suggested for diagnosis and therapy of gout, hyperuricemia and the Lesch-Nyhan syndrome. In order to investigate the correlation between trace amounts of UA in human saliva and urine and explore the potential application in fast diagnosis of gout, capillary electrophoresis with electrochemical detection (CE-ED) was applied for the determination of UA in human saliva and urine in this work. Under the optimum conditions, UA and three coexisting analytes could be well separated within 14 min at the separation voltage of 14 kV in 80 mmol L(-1) borax running buffer (pH 7.8). A good linear relationship was established between peak current and concentration of analytes over two orders of magnitude with detection limits (S/N = 3) ranging from 1.09 x 10(-7) to 5.0 x 10(-7) mol L(-1) for all analytes. This proposed method has been successfully applied for study of the correlation between the UA content of human saliva and urine, providing an alternative and convenient method for rapid diagnosis of gout.