Potentiometric sensor based on novel flowered-like Mg-Al layered double hydroxides/multiwalled carbon nanotubes nanocomposite for bambuterol hydrochloride determination.

Nowadays, development of highly efficient potentiometric sensors attracts the attention of many researchers over the world; due to the great expansion of portable analytical devices. This study aims to apply a current development to the construction and sense of carbon paste sensors based on flowered-like Mg-Al layered double hydroxides/multiwalled carbon nanotubes (FLLDH/MWCNTs) (sensor І), FLLDH/titanate nanotubes (TNTs) (sensor ІІ) and MWCNTs/TNTs (sensor ІІІ) nanocomposites for bambuterol hydrochloride analysis; to enhance the potentiometric response towards determination of the drug. The sensors exhibited excellent Nernstian slopes 58.8 ±â€¯0.5, 58.5 ±â€¯0.8 and 57.4 ±â€¯0.7 mV/decade with linear working ranges of 1.0 × 10-7-1.0 × 10-2, 1.0 × 10-6-1.0 × 10-2 and 1.0 × 10-7-1.0 × 10-2 mol L-1, detection limits 2.3 × 10-8, 2.5 × 10-7and 7.5 × 10-8 mol L-1 and quantification limits of 7.6 × 10-8, 8.3 × 10-7and 2.5 × 10-7 mol L-1 for sensor І, ІІ and ІІІ, respectively. The selectivity behaviour of the investigated sensors was tested against biologically important blood electrolytes (Na+, K+, Mg2+, Ca2+). The proposed analytical method was successfully applied for BAM determination in pure drug, pharmaceutical products, surface water, human plasma and urine samples with excellent recovery data (99.62, 99.10 and 98.95%) for the three sensors, respectively.

Terbutaline Accumulates in Blood and Urine after Daily Therapeutic Inhalation.

PURPOSE: This study investigated pharmacokinetics of terbutaline after single and seven consecutive days of inhalation in exercising trained men. METHODS: Twelve healthy trained men underwent two pharmacokinetic trials comparing single dose (2 mg) and seven consecutive days (2 mg·d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 55%-65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Maximum serum concentration of terbutaline (Cmax) (6.4 ± 1.2 vs 4.9 ± 1.2 ng·mL, P = 0.01) (mean ± 95% confidence interval) and area under serum concentration-time curve from 0 to 4 h after inhalation (AUC0-4) (16 ± 3 vs 13 ± 2 ng·mL·h, P ≤ 0.005) were higher after 7 d of inhalation compared with the first day. Seven days of terbutaline inhalation resulted in accumulation of terbutaline in urine, in which total urine excretion of terbutaline was higher after 7 d of inhalation compared with the first day (274 ± 43 vs 194 ± 33 µg, P ≤ 0.001). These differences were partly attributed to systemic accumulation of terbutaline after consecutive days of inhalation, in that baseline serum and urine samples revealed incomplete elimination of terbutaline. CONCLUSION: Terbutaline accumulates in serum and urine after consecutive days of inhalation. For doping control purposes, these observations are of relevance if a urine threshold and decision limit is to be introduced for terbutaline on the World Anti-Doping Agency's list of prohibited substances because asthmatic athletes may use their bronchorelievers for consecutive days.

Molecularly imprinted phloroglucinol-formaldehyde-melamine resin prepared in a deep eutectic solvent for selective recognition of clorprenaline and bambuterol in urine.

A new molecularly imprinted phloroglucinol-formaldehyde-melamine resin (MIPFMR) was synthesized in a deep eutectic solvent (DES) using phenylephrine as a dummy template. The MIPFMR was used as a solid phase extraction (SPE) sorbent for the selective isolation and recognition of clorprenaline (CLP) and bambuterol (BAM) in urine. Phloroglucinol and melamine were used as double functional monomers that introduced abundant hydrophilic groups (such as hydroxyl groups, imino groups, and ether linkages) into the MIPFMR, making it compatible with aqueous solvents. In addition, the formation of DES by combining the quaternary ammonium salt of choline chloride with ethylene glycol as a hydrogen bond donor was an environmentally safe alternative to toxic organic solvents such as chloroform and dimethylsulfoxide that are typically used in the preparation of most molecularly imprinted polymers (MIPs). Moreover, MIPFMR-based SPE of CLP and BAM in urine resulted in higher recoveries and purer extracts than those obtained by using other SPE materials (e.g., SCX, C18, HLB, and non-imprinted phloroglucinol-formaldehyde-melamine resin (NIPFMR)). The optimized MIPFMR-SPE-HPLC-UV method had good linearity (r2 ≥ 0.9996) ranging from 15.0 to 3000.0 ng mL-1 for CLP and BAM, and the recoveries at three spiked levels ranged from 91.7% to 100.1% with RSDs ≤7.6%. The novel MIPFMR-SPE-HPLC-UV method is simple, selective, and accurate, and can be used for the determination of CLP and BAM in urine samples.

Influence of exercise in normal and hot ambient conditions on the pharmacokinetics of inhaled terbutaline in trained men.

This study investigated the pharmacokinetics of inhaled terbutaline at rest and after exercise in normal and hot ambient conditions with respect to doping analysis. Thirteen trained young men participated in the study. Urine and blood samples were collected after inhalation of 4 mg terbutaline during three trials: exercise in hot ambient conditions (30-35 °C) (EXH), exercise in normal ambient conditions (20-25 °C) (EX), and rest (20-25 °C) (R). Exercise consisted of 130 min at various intensities. Adjustment of urine concentrations of terbutaline to a specific gravity (USG) of 1.02 g/mL was compared with no adjustment. Area under the serum concentration-time curve within the first 6 h was higher for EX (27 ± 3 ng/mL/h) (P ≤ 0.01) and EXH (25 ± 4 ng/mL/h) (P ≤ 0.05) than for R (20 ± 3 ng/mL/h). When unadjusted for USG, urine concentrations of terbutaline after 4 h were different in the order EXH > EX > R (P ≤ 0.01). When unadjusted for USG, urine concentrations of terbutaline were 299 ± 151 ng/mL higher (P ≤ 0.001) after 4 h compared with adjusted concentrations in EXH. Excretion rate of terbutaline was higher (P ≤ 0.001) for EX than for EXH and R within the first 0-1½ h. In conclusion, EXHs results in higher urine concentrations of terbutaline. This should be considered when evaluating doping cases of terbutaline.

Terbutaline: level the playing field for inhaled ß2-agonists by introducing a dosing and urine threshold.

Terbutaline, a short-acting ß2-agonist similar to salbutamol, is widely used in Europe in the treatment of asthma and exercise-induced bronchoconstriction. Unlike salbutamol, terbutaline requires therapeutic use exemption (TUE) for therapeutic inhaled use in competitive sport. There is now compelling evidence that supratherapeutic use of terbutaline is performance enhancing, via oral dosing and inhalation. It is likely that the ergogenic effects of terbutaline are class specific for all ß2-agonists. The World Anti-Doping Agency (WADA) has introduced dosing and urine threshold and decision limits for other common ß2-agonists. This allows athletes to use these drugs for therapeutic purposes while minimising the potential for doping and administrative burden of TUEs. However, no such threshold limits currently exist for terbutaline. For terbutaline, athletes can be granted a TUE, then administer the drug via inhalation at supratherapeutic doses with impunity. The introduction of threshold dosing and urine limits for terbutaline should be a high priority, given the drug's demonstrated ergogenic effects.

A sensitive LC-MS/MS method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine with application to a clinical pharmacokinetic study.

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine was established. The inhibition for the biotransformation of R-bambuterol in plasma was fully investigated. Plasma samples were prepared on ice and neostigmine metilsulfate added as a cholinesterase inhibitor immediately after sample collection. All samples were extracted with ethyl acetate and separated on a C18 column under gradient elution with a mobile phase consisting of methanol and water containing 5 mm ammonium acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma. In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R-bambuterol and R-terbutaline, respectively. The intra- and inter-day precisions were <12.7 and <8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min per sample made this method suitable for high-throughput determination. The validated method has been successfully applied to the human pharmacokinetic study of R-bambuterol involving 10 healthy volunteers.

Pharmacokinetics of terbutaline in chronic kidney disease.

PURPOSE: In healthy individuals upwards of 90 % of an injected dose of terbutaline is excreted in the urine. The purpose of this study is to determine the pharmacokinetic properties of terbutaline in patients with severe renal impairment as defined by a glomerular filtration rate (GFR) below 30 mL/min. METHODS: Ten patients were included in the study. GFR was measured with Cr-EDTA clearance. They were given an intravenous injection of 0.500 mg of terbutaline. Blood samples were collected at intervals for 60 h and urine samples were collected for 96 h. The concentration of terbutaline in the blood and in the urine was used to calculate pharmacokinetic parameters. RESULTS: In patients with normal renal function the total clearance of terbutaline is 2.23-3 mL/min/kg. In our population the total clearance of terbutaline was found to be 1.72 (SD: 0.49) mL/min/kg of which approximately 15 % (0.25 mL/min/kg) was renal clearance. We calculated a distribution volume at steady state of 0.74 (SD: 0.22) L/kg with a terminal half-life of 7.93 (SD: 4.06) hours. The mean residence time (MRT) was 8.35 (SD: 4.93) hours. CONCLUSIONS: In healthy individuals the excretion of terbutaline is foremost renal but this study shows that severe renal impairment does not lower the total clearance of terbutaline to a degree that might be expected from the Cr-EDTA clearance. However, more research is needed to determine if dosage adjustment is warranted in patients with CKD.

Detection of main urinary metabolites of ß2-agonists clenbuterol, salbutamol and terbutaline by liquid chromatography high resolution mass spectrometry.

Clenbuterol, terbutaline and salbutamol are B2-agonists drugs included in the list of banned substances of the World Anti Doping Agency (WADA) prohibited in and out of competition. In this article, the excretion of urinary metabolites of clenbuterol, terbutaline and salbutamol have been studied using liquid chromatography electrospray time-of-flight mass spectrometry (LC-TOFMS), after a single therapeutic dose administration in rats. Urine collected was processed with solid-phase extraction prior to LC-TOFMS analyses using electrospray in the positive ion mode and pseudo MS/MS experiments from in-source collision induced dissociation (CID) fragmentation (without precursor ion isolation). The strategy applied for the identification of metabolites was based on the search of typical biotransformations with their corresponding accurate mass shift and the use of common diagnostic fragment ions from the parent drugs. The approach was satisfactory applied, achieving the identification of 11 metabolites (5 from clenbuterol, 4 from salbutamol and 3 from terbutaline), 4 of them not previously reported in urine. Novel metabolites identified in rat urine included N-oxide-salbutamol, hydroxy-salbutamol, methoxy-salbutamol glucuronide and terbutaline N-oxide, which are all reported here for the first time.

Urine and serum concentrations of inhaled and oral terbutaline.

We examined urine and serum concentrations after therapeutic use of single and repetitive doses of inhaled and supratherapeutic oral use of terbutaline. We compared the concentrations in 10 asthmatics and 10 healthy subjects in an open-label, cross-over study with 2 mg inhaled and 10 mg oral terbutaline on 2 study days. Further, 10 healthy subjects were administrated 1 mg inhaled terbutaline in 4 repetive doses with total 4 mg. Blood samples were collected at baseline and during 6 h after the first inhalations. Urine samples were collected at baseline and during 12 h after the first inhalations. Median (IQR) urine concentrations peaked in the period 0-4 h after inhalation with Cmax 472 (324) ng/mL in asthmatics and 661 (517) ng/mL in healthy subjects, and 4-8 h after oral use with Cmax 666 (877) ng/mL in asthmatic and 402 (663) ng/mL in healthy subjects. In conclusion we found no significant differences in urine and serum concentrations between asthmatic and healthy subjects. We compared urine and serum concentrations after therapeutic inhaled doses and supratherapeutic oral doses and observed significant statistical differences in both groups but found it impossible to distinguish between therapeutic and prohibited use based on doping tests with urine and blood samples.

Chemiluminescence determination of terbutaline sulfate in bovine urine and pharmaceutical preparations based on enhancement of the 2-phenyl-4, 5-di (2-furyl) imidazole-potassium ferricyanide system.

In this paper, a novel chemiluminescence (CL) system, 2-phenyl-4, 5-di (2-furyl) imidazole (PDFI)-potassium ferricyanide, for the determination of terbutaline sulfate was described. The method was based on enhancement of CL emission of PDFI-potassium ferricyanide system in the presence of terbutaline sulfate. Under the optimum conditions, the enhanced chemiluminescence intensity is linearly related to the concentration of terbutaline sulfate. The proposed method has been successfully applied to the determination of terbutaline sulfate in bovine urine and pharmaceutical preparations with satisfactory results. Furthermore, the possible mechanism of chemiluminescence reaction was also discussed briefly.

The relative lung and systemic bioavailability of terbutaline following nebulisation in non-invasively ventilated patients.

Nebulising a bronchodilator during non-invasive ventilation (NIV) is effective but there is a lack of consensus on the system to use because comparator in vivo studies in these patients are difficult. Urinary pharmacokinetic methodology post inhalation could provide this information. Chronic obstructive pulmonary disease patients requiring NIV received randomised study doses of either 2mg terbutaline nebulised from an Aeroneb Pro (AERO) or 5mg from a Sidestream (SIDE) on days 1 and 3 of admission. Urine samples were provided at 30 min then pooled up to 24h post inhalation and amounts of urinary terbutaline (UTER0.5 and UTER24; indices of relative lung and systemic bioavailability, respectively) were determined. Twelve consenting patients receiving NIV mean (SD) age and weight of 74.8 (8.2) years and 61.0 (10.7)kg completed the study. The mean (SD) UTER0.5 following AERO and SIDE was 9.4 (3.7) and 10.4 (4.1) µg with a mean ratio (90% confidence interval) of 89.7 (87.8, 92.3)%. UTER24 was 192.3 (52.4) and 205.3 (58.0)mcg with a mean ratio (90% CI) of 93.7 (113.5, 77.3)%. This urinary pharmacokinetic method to identity relative lung and systemic bioavailability between two nebuliser systems was easy to perform and is a useful and simple in vivo method to compare different nebulisers in patients receiving non-invasive ventilation.

Relative bioavailability of terbutaline to the lung following inhalation, using urinary excretion.

AIMS: The aim of the study was to determine the relative lung and systemic bioavailability of terbutaline. METHODS: On separate days healthy volunteers received 500 µg terbutaline study doses either inhaled from a metered dose inhaler or swallowed as a solution with and without oral charcoal. Urine samples were provided at timed intervals post dosing. RESULTS: Mean (SD) urinary terbutaline 0.5 h post inhalation, in 12 volunteers, with (IC) and without (I) oral charcoal and oral (O) dosing was 7.4 (2.2), 6.5 (2.1) and 0.2 (0.2) µg. I and IC were similar and both significantly greater than O (P<0.001). Urinary 24 h terbutaline post I was similar to IC + O. The method was linear and reproducible, similar to that of the urinary salbutamol method. CONCLUSIONS: The urinary salbutamol pharmacokinetic method post inhalation applies to terbutaline. Terbutaline study doses can replace routine salbutamol during these studies when patients are studied.

[Determination of fifteen beta-agonists in animal urine by high performance liquid chromatography-tandem mass spectrometry].

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS) method was established for the determination of fifteen beta-agonists (clenbuterol, ractopamine, salbutamol, cimaterol, mabuterol, tulobuterol, bambuterol, mapenterol, cimbuterol, zilpaterol, formoterol, clorprenaline, terbutaline, penbutolol and brombuterol) in animal urine. Perchloric acid solution was used to acidify the sample and precipitate protein in the sample. The sample was purified and concentrated by an HLB mini-column. The separation of the beta-agonist was performed on an Agilent 1100 HPLC system with a Eclipse XDB-C18 column by using gradient elution with methanol and water (containing 0.1% (v/v) formic acid) as the mobile phases at a flow rate of 1 mL/min. Qualitative and quantitative analysis of the fifteen beta-agonists, which were ionized by electrospray ionization interface (ESI), were carried out in multiple reaction monitoring (MRM) mode with API 4000 tandem mass spectrometry. The calibration curves showed good linearity in the mass concentration range of 0.25 - 20 microg/L with the correlation coefficients r > or = 0.999 5. The recoveries of the fifteen beta-agonists ranged from 62.1% to 107% at the spiked levels of 0.25, 1.0 and 10 microg/L. The relative standard deviations (n = 10) were between 3.5% and 9.9%. The limits of quantification (S/N > 10) were 0.25 microg/L for all the analytes. This method is simple, rapid, sensitive and accurate.

Emitted dose and lung deposition of inhaled terbutaline from Turbuhaler at different conditions.

Turbuhaler has a very high resistance hence patient inhalation flow when using it would be low. The total emitted dose (TED) of 500microg terbutaline sulphate from a Bricanyl Turbuhaler was determined using a range of inhalation flows (10-60L min(-1)) with inhalation volume of 2 and 4L using a DPI sampling apparatus after one and two inhalations. The relative lung and systemic bioavailability of terbutaline from Bricanyl Turbuhaler when used by healthy subjects and COPD patients were determined after one and two inhalations at slow and fast inhalation flows using a novel urinary terbutaline pharmacokinetic method. The TED resulted from the one and two inhalations increased significantly (p<0.05) with the increase of the inhalation flow at both 2 and 4L inhalation volumes. The relative lung and systemic bioavailability after one inhalation at fast inhalation flow were significantly higher (p<0.01) than at slow inhalation flow in both healthy subjects and patients. Also the healthy subjects results were significantly higher (p<0.05) than the COPD patients after one inhalation. However after two inhalations there was no significant difference between slow and fast inhalation flow or healthy subjects and COPD patients. Hence it is essential to inhale twice and as deep and hard as possible from each dose of Turbuhaler for patients with low inspiratory flow and limited inhalation volume as they may not receive much benefit from one inhalation.

Determination of terbutaline sulfate by capillary electrophoresis with chemiluminescence detection.

A novel capillary electrophoresis (CE) with chemiluminescence (CL) detection method for determination of terbutaline sulfate has been developed. This method is based on the chemiluminescence reaction of potassium ferricyanide with luminol in sodium hydroxide medium sensitized by terbutaline sulfate. With the peak height as a quantitative parameter applying optimum working conditions, terbutaline sulfate is determined over the range of 7.0 x 10(-8) to 3.6 x 10(-6)M with a detection limit of 3.0 x 10(-8)M. The relative standard deviation (RSD) was 4.6% for 6.0 x 10(-7)M terbutaline sulfate (n=11). The proposed method has been applied to determination of terbutaline sulfate in commercial terbutaline sulfate drug and spiked in human urine with satisfactory results.

Terbutaline sulfoconjugate: characterization and urinary excretion monitored by LC/ESI-MS/MS.

Terbutaline is a fast-acting beta(2)-adrenergic agonist used in the treatment of obstructive pulmonary diseases. Doping control for beta(2)-agonists, which are forbidden in sports by the World Anti-doping Agency (WADA), is performed in screening by liquid chromatography/mass spectrometry after hydrolysis of phase-II metabolites. In this study, the mono-sulfoconjugated phase-II metabolite of terbutaline was synthesized and the chemical structure was characterized by (1)H-nuclear magnetic resonance spectrometry and high resolution/high accuracy Orbitrap mass spectrometry. The metabolite was designated as the phenolic esterified compound, which has been mentioned in most literature reports but has not been verified so far. The benzylic esterified compound was also synthesized and characterized by high-resolution/high accuracy Orbitrap mass spectrometry but was not detectable in urine samples from an excretion study performed after a single application of one terbutaline capsule (7.5 mg terbutaline sulfate salt). The phenolic sulfate of terbutaline was detected for two to four days after administration, whereas the unchanged terbutaline was detected for four to five days. A glucuronidated, disulfated or trisulfated phase-II metabolite of terbutaline was not found. The measurement of phase-II metabolites is planned to be incorporated into existing screening procedures to allow a faster sample preparation.

Electrostacking online sample pre-concentration capillary electrophoresis with amperometric detection for beta2-agonists in human urine.

A simple, rapid, sensitive and specific method using capillary electrophoresis (CE) coupled with electrostacking and amperometric detection (AD) has been developed for the simultaneous separation and determination of clenbuterol (CLB), terbutaline (TER), salbutamol (SAL) and formoterol (FMT). In this paper, the CE separation and AD conditions were investigated in detail. The optimum conditions were: pH 8.6 Na(2)B(4)O(7)-H(3)BO(3) buffer solution (20.0 mmol/L), 9 kV for the separation voltage, and 1000 mV (versus Ag/AgCl) for the detection potential. When the sample which was dissolved in 70% ACN-water mixture solution was injected 60 s by 15 kV electrokinetic injection, the best stacking effects was obtained. Under the optimum conditions, the enhancement factors of these beta(2)-agonists had been greatly improved more than 5500-fold compared with the conventional electrokinetic injection. And then an excellent linear response was obtained with LODs (S/N = 3) of 0.098, 0.024, 0.063 and 0.920 pmol/L for CLB, TER, SAL and FMT in urine, respectively. The precision was determined in both intra-day (n = 5) and inter-day (n = 15) assays, and the RSDs were not more than 2.1 and 3.4% for migration time and peak current, respectively. The proposed method has been applied to analyze human urine samples successfully.

[Simultaneous determination of nine beta2-agonists residues in urines by ultra performance liquid chromatography-electrospray tandem mass spectrometry].

OBJECTIVE: To study the determination method of nine beta2-agonists residues in urine. METHODS: Urine samples were duconjugated with beta-glucuronidase/arylsulfatase enzyme in acetate buffer and deproteinized by perchloric acid, and then adjusted pH4.0. Sample concentration and purification were performed by Oasis HLB, Oasis MCX. The separation was performed on a Waters ACQUITY UPLCTM BEH C18 column (100mm x 2.1mm i.d., 1.7microm) with gradient elution using methanol and water (containing 0.1% formic acid) at a flow rate of 0.3ml/min. RESULTS: The limits of detection (LOD) of the method were from 0.002 to 0.025ng/ml and the limits of quantification (LOQ) ranged from 0.007 to 0.08ng/ml. Average recoveries for nine beta2-agonists at the spiking levels of 0.1, 0.5 and 2ng/ml ranged from 77.4% to 101.7% with relative standard deviations between 3.4% and 18% . CONCLUSION: The method can be used to determine the residues of nine beta2-agonists in urines.

Determination of terbutaline enantiomers in human urine by capillary electrophoresis using hydroxypropyl-beta-cyclodextrin as a chiral selector.

A method for the determination of terbutaline enantiomers in human urine by capillary electrophoresis has been developed. Optimum resolution was achieved using 50 mM phosphate buffer, pH 2.5, containing 15 mM of hydroxypropyl-beta-cyclodextrin as a chiral selector. Urine samples were prepared by solid-phase extraction with Sep-pak silica, followed by CE. The assay was linear between 2-250 ng/mL (R = 0.9998 for (S)-(+)-terbutaline and R = 0.9999 for (R)-(-)terbutaline) and detection limit was 0.8 ng/mL. The intra-day variation ranged between 6.3 and 14.5% in relation to the measured concentration and the inter-day variation was 8.2-20.1%. It has been applied to the determination of (S)-(+)terbutaline and (R)-(-)-terbutaline in urine from healthy volunteer dosed with racemic terbutaline sulfate.

Quantification of terbutaline in urine by enzyme-linked immunosorbent assay and capillary electrophoresis after oral and inhaled administrations.

The International Olympic Committee and World AntiDoping Agency restricts the use of beta2-agonists and only the inhaled administration of terbutaline, salbutamol, formoterol and salmeterol is permitted for therapeutic reasons. The aim of this study was to develop a test for the quantitation of terbutaline in urine and evaluate different parameters to distinguish between oral and inhaled administration of the drug. Urine samples were collected from asthmatic and non-asthmatic recreational swimmers who had received repeated doses of oral (3x2.5 mg plus 1x5 mg during 24 h) and inhaled (12x0.5 mg in 24 h with half of it being in the last 4 h) racemic terbutaline, and single oral (5 mg) or single inhaled doses (1 mg). Total terbutaline concentrations (free+conjugated) were determined by enzyme-linked immunosorbent assay. Results showed that after oral administrations urinary terbutaline concentrations were higher than those detected after inhalation. For confirmation purposes, a chiral capillary electrophoretic procedure was established and validated. A solid-phase extraction with Bond-Elut Certify cartridges was undertaken, separation performed using a 50 mM phosphate buffer (pH 2.5) containing 10 mM of (2-hydroxypropyl)-beta-cyclodextrin as running buffer and diode-array UV detection set at 204 nm. The proposed procedure is rapid, selective and sensitive allowing quantitation of free terbutaline enantiomers in urine. No statistical differences were found between total free terbutaline concentrations [S-(+)+R-(-)] in urine collected after oral and inhaled administrations of the drug. After oral doses enantiomeric [S-(+)]/[R-(-)] ratios lower than those obtained after inhalation were observed probably due to an enantioselective metabolism that take place in the intestine, but differences between both routes of administration were not statistically significant. Although different trends were observed after oral and inhaled doses in total terbutaline, total free terbutaline concentrations and in ratios between its enantiomers, differences observed were not sufficiently significant to establish cut-off values to clearly distinguish between both routes of administration.