Bergés R, Segura J, Ventura R, Fitch K D, Morton A R, Farré M, Mas M, de La Torre X
Pharmacology Research Unit, Institut Municipal d'Investigació Mèdica (IMIM), Doctor Aiguader 80, 08003 Barcelona, Spain.
Clin Chem. 2000 Sep;46(9):1365-75.
The administration of salbutamol is permitted only by inhalation by the International Olympic Committee (IOC) for the management of asthma and exercise-induced asthma in athletes. The establishment of criteria to distinguish between the (IOC) authorized use (inhaled) and the (IOC) prohibited use (oral) of salbutamol appeared possible using simultaneous evaluation of variables based on the concentration of nonconjugated enantiomers of salbutamol excreted in urine.
Urine was collected from asthmatic and nonasthmatic swimmers who had received various preexercise doses of oral (five doses of 4 mg) or inhaled (two doses of 100 microgram) salbutamol. Urine was also obtained from subjects who had received the maximum dosage of inhaled salbutamol advisable for competing athletes to provide protection from exercise-induced asthma and treatment of asthma (1600 microgram in 24 h, 800 microgram being in the last 4 h). All samples were analyzed to determine the total amount of unchanged salbutamol excreted in urine and the ratio between the S: and R: enantiomers.
The discriminant function D = -3.776 + 1.46 x 10(-3) ([S:(+)] + [R:(-)]) + 1.012 ([S:(+)]/[R(-)]) can be used to classify data into two groups, inhaled and oral. The confirmatory criterion suggested (cutoff at D = 1.06, 4 SD from the mean D value of the inhaled distribution) has been verified in different sets of samples showing suspicious concentrations by conventional screening procedures in doping control. An 11.8% false-negative (oral classified as inhaled) rate is assumed with the confirmatory criterion proposed, but virtually no false positives (inhaled classified as oral) are obtained (<1 in 33 000).
The overall procedure recommended is to screen all samples and to apply the confirmation criterion proposed to samples showing free racemic salbutamol concentrations >500 microgram/L by gas chromatography-mass spectrometry or free + conjugated racemic salbutamol concentrations >1400 microgram/L by ELISA.
国际奥委会（IOC）仅允许通过吸入方式使用沙丁胺醇来治疗运动员的哮喘和运动诱发的哮喘。通过同时评估基于尿中排泄的沙丁胺醇非共轭对映体浓度的变量，似乎有可能建立区分国际奥委会授权使用（吸入）和国际奥委会禁止使用（口服）沙丁胺醇的标准。
从接受过各种运动前口服（五剂4毫克）或吸入（两剂100微克）沙丁胺醇剂量的哮喘和非哮喘游泳运动员中收集尿液。尿液还取自接受了对参赛运动员预防运动诱发哮喘和治疗哮喘建议的最大吸入剂量沙丁胺醇的受试者（24小时内1600微克，最后4小时内800微克）。分析所有样本以确定尿中排泄的未变化沙丁胺醇总量以及S：和R：对映体之间的比例。
判别函数D = -3.776 + 1.46×10⁻³（[S：(+)] + [R：(-)]）+ 1.012（[S：(+)] / [R(-)]）可用于将数据分为吸入和口服两组。所建议的确认标准（D = 1.06时截断，距吸入分布的平均D值4个标准差）已在不同组的样本中得到验证，这些样本通过兴奋剂检测中的常规筛查程序显示出可疑浓度。采用所提出的确认标准时，假阴性率（口服误分类为吸入）为11.8%，但几乎没有假阳性（吸入误分类为口服）（每33000例中少于1例）。
推荐的总体程序是筛查所有样本，并将所提出的确认标准应用于通过气相色谱 - 质谱法显示游离外消旋沙丁胺醇浓度>500微克/升或通过酶联免疫吸附测定法显示游离 + 共轭外消旋沙丁胺醇浓度>1400微克/升的样本。
