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Beta-blockers have been prohibited by the World Anti-Doping Agency (WADA) in certain sports, but insufficient research data make it difficult to distinguish between therapeutic uses or misuses. This study aimed at investigating the urinary excretion pattern following beta-blocker ophthalmic drops and the potential risk of constituting an adverse analytical finding (AAF) in sports. Prescribed timolol and carteolol ophthalmic drops were used in healthy participants and glaucoma patients. The urine samples were then collected to investigate the urinary excretion pattern following acute and chronic administration of the above beta-blocker ophthalmic drops. The liquid chromatograph-tandem mass spectrometry method was applied for measuring urinary beta-blockers. Our results demonstrated that the levels of both urinary timolol and carteolol exceeded the minimum reporting levels (MRL) following acute and chronic administration. The highest levels of urinary timolol and carteolol observed in the present study were 255.7 and 923.8 ng/ml, respectively. Regarding the acute administration of timolol ophthalmic drop, 26.19 (11/42) of urine samples were detected with timolol higher than the MRL in timed and random sampling. In contrast, the acute administration of carteolol ophthalmic drops made the carteolol levels higher than the MRL among most urine samples. On the other hand, 36.36% (4/11) of urine samples were detected with beta-blockers higher than the MRL during the chronic administration of timolol and carteolol ophthalmic drops. In the context of receiving ophthalmic beta-blocker medications, the present study has highlighted the potential risk of constituting an AAF in specific sports and suggests strengthening athletes' awareness of therapeutic use exemptions.

Triamcinolone (T) is a glucocorticoid commonly used to relieve inflammation and treat arthritis, severe allergies, and asthma; however, it is banned by the World Anti-Doping Agency in competition for athletes when administered orally, intravenously, intramuscularly, or rectally. The minimum required performance limit (MRPL) for urinary T is 30 ng/mL. However, the data about the urinary excretion of T after oral administration is limited. We investigate the elimination profile and determine whether single-dose administration of T would cause a positive doping result. Twelve healthy volunteers received a single-dose of 4-mg T rally, and urine samples were collected for 24 hours. A validated liquid chromatography-tandem mass spectrometry method was used to determine urinary T levels. Non-compartmental modeling was used to estimate the pharmacokinetic parameters. All the urinary T concentrations were much higher than the MRPL. The peak urinary T concentration was 3211.4 ± 860.3 ng/mL (mean ± SD), time to peak concentration was 1.7 ± 0.9 hours, and the estimated elimination half-life was 4.4 ± 2.8 hours. About 27.76% of the consumed dose was eliminated via urine within 24 hours of intake. After a single-dose oral administration, urinary T concentrations still exceeded the MRPL after 24 hours. This information could be useful for limiting the misuse of T. Athletes should be aware when using T in competition and acquire approval for a therapeutic use exemption prior to use. Moreover, the elimination profile of orally administered T may be crucial information for distinguishing different dosage routes.

Hemp nuts are mature cannabis seeds obtained after hulling and stir-frying that are commonly used in traditional Chinese medicine for treating functional constipation. In this work, we screened hemp nut products, classified them, and verified the legality of consuming them. A total of 18 products were purchased from Taiwan, China and Canada. Validated high-performance liquid chromatography with tandem mass spectrometry methods were developed for analyzing the cannabinoid (i.e., Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol) content of the products and the concentration of urinary 11-nor-9-carboxy-THC. Chemometric techniques, namely hierarchical clustering analysis (HCA) and principal component analysis (PCA), were applied for rapidly classifying 11 concentrated powder products in Taiwan. A pilot human study comprising single and multiple administrations of a product with 1.5 µg/g of THC was conducted to examine the urinary 11-nor-9-carboxy-THC concentration. Through optimization of 32 full factorial design, using 60% isopropanol as the extraction solvent exhibited the highest yield of cannabinoids and was applied as the optimal condition in further analysis. The results of HCA and PCA on quality evaluation were in well agreement; however, the tested products possessed distinct CBD-to-THC ratios which ranged widely from 0.1:1 to 46.8:1. Particularly, the products with CBD-to-THC ratios higher than 1:1 were the majority in Taiwan. Our data suggested that all the tested hemp nut products met the Taiwan restriction criteria of 10 µg/g of THC. We propose a usual consumption amount of hemp nut products in Taiwan would unlikely to violate the cut-off point of 15 ng/mL of urinary 11-nor-9-carboxy-THC. This article is protected by copyright. All rights reserved.

The purpose of the study was to investigate the effects of swimming on the pharmacokinetic and insulin sensitivity of metformin in insulin resistant rats. Rats with fructose-induced insulin resistance were assigned into four groups: control group (C, n=8), metformin group (M, n=8), swimming group (S, n=8) and metformin with swimming group (MS, n=8). After 12 h of fasting, the S and MS group swam for 45 min, while the M and C groups were placed in 4 cm deep water for the same time period. The first blood samples were withdrawn from the tail 60 min after the four groups had left the water. An oral glucose loading was performed in all groups and metformin was administered to the M and MS groups after the first blood sample. Blood samples were collected at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10 and 12 h. The results showed that the MS group increased the time to the maximum concentration, the time to half-life concentration and enhanced insulin sensitivity. This study suggests that swimming before administration of metformin significantly improved insulin sensitivity and the rate of metformin absorption. Copyright © 2008 John Wiley & Sons, Ltd.

Cat's claw is a large woody vine with hook-like thorns, and has been traditionally used to treat inflammatory disorders in South and Central America. In this study, a rapid, validated high-performance liquid chromatographic (HPLC) method using a silica monolithic column was developed for the simultaneous determination of oxindole alkaloids, namely rhynchophylline, pteropodine, isomitraphylline and isopteropodine, in cat's claw. The ionic liquid-based microwave-assisted extraction (ILMAE), considered as an environmentally friendly and powerful tool, was first applied in the extraction of oxindole alkaloids. To optimize the HPLC method, the stationary phases, pH values of mobile phase and flow rates were investigated. The validated HPLC method using a Monolithic RP18e column (100 × 4.6 mm) enables these analytes to be separated almost twice as fast as with a conventional particulate column (~16 vs ~30 min) with limits of quantification and detection of 0.5 and 0.15 μg/mL, respectively. The ILMAE conditions were optimized by the Taguchi orthogonal array design. In comparison with conventional water boiling extraction, ILMAE offers almost four times higher yields within an extremely short extraction time. The developed HPLC coupled with ILMAE method could be efficient and practical for rapid determination of oxindole alkaloids in cat's claw.