Salbutamol In Plasma Research Articles

Green potentiometric electrode for determination of salbutamol in biological samples

Clinical drug analyses and identification of pharmaceuticals in biological samples are highly crucial for therapeutic drug monitoring, pharmacokinetic studies, and screening of illicit drugs. Various analytical tools, such as potentiometric electrodes, are used to conduct these investigations. These potentiometric electrodes are superior to other techniques in terms of greenness and cost efficacy, and thus present a good alternative for researchers. In this study, we develop an advanced electrode for the in-situ monitoring of salbutamol in plasma, this electrode was synthesized using multiwalled carbon nanotubes (MWCNT) as hydrophobic conductive substance and copper oxide nanoparticle (CuO NP) as a surface modifier, the developed electrode was compared to traditional liquid contact electrode as well as solid contact electrode and proved its superiority. The use of MWCNT improved the stability of the electrode via preventing the formation of this water layer and the CuO NP improved the sensitivity due to its high surface area and rich electronic properties. CuO NP modified electrode was used for the determination of salbutamol with a Nernstian slope of 57.4 over a linearity range of range 1.0 × 10−7- 1.0 × 10−2 M, and a detection limit of 4.0 × 10−7 M. The proposed electrode was effectively applied for the determination of the cited drug in rat plasma without interference and compared with chromatographic reported method. The proposed method is economic as it has a low sample analysis cost, time saving and needs fewer manipulation steps and a simple convenient device. It also proved to be a greener method when compared with chromatographic methods using an eco-scale metric system.

Model-based meta-analysis of salbutamol pharmacokinetics and practical implications for doping control.

Salbutamol was included in the prohibited list of the World Anti‐Doping Agency (WADA) in 2004. Although systemic intake is banned, inhalation for asthma is permitted but with dosage restrictions. The WADA established a urinary concentration threshold to distinguish accordingly prohibited systemic self‐administration from therapeutic prescription by inhalation. This study aimed at evaluating the ability of the WADA threshold to differentiate salbutamol therapeutic use from violation of antidoping rules. Concentration‐time profile of salbutamol in plasma and its excretion in urine was characterized through a model‐based meta‐analysis of individual and aggregate data collected after administration of a large range of doses following different modes of administration and under a variety of conditions. The developed model adequately fitted salbutamol plasma and urine concentration‐time profiles of the 13 selected studies. Model‐based simulations confirmed that a wide range of salbutamol urine concentrations might be measured after drug intake. Although violation of the WADA Code can be strongly suspected in individuals showing very high salbutamol urine concentrations, uncertainty remains for values close to the WADA threshold as they can be compatible with both permitted therapeutic use and violation. Although not entirely discriminant, the current WADA rule is globally supported by our appraisal. It could be further improved by a slight and reasonable adjustment of inhaled daily dosages allowed for therapeutic use. Our model might help antidoping experts in the evaluation of suspected doping cases through confronting the athlete's urine measurements with their allegations about salbutamol treatment.

Salbutamol Residue in Plasma and Urine of Balinese Calves after Single-Dose Administration

Salbutamol, a short-acting β2-adrenergic receptor agonist, due to illegal use in animal feed, is very dangerous for the safety of animal origin products. The purpose of this study is to determine the residue of salbutamol in plasma and urine of balinese calf after a single-dose administration. Three calves were given of feed fortification of salbutamol (10 mg/kg body weight). The salbutamol concentrations were measured in the plasma and urine. Samples were extracted with perchloric acid and purified by cation exchange solid phase extraction (SPE), then analyzed by High-Performance Liquid Chromatography (HPLC) with a photodiode array detector using an RP C18 column with a mixed mobile phase of purified water pH 3.0 (adjusted with phosphoric acid) and acetonitrile (90:10, v/v). The highest salbutamol concentration in the plasma sample was 0.28±0.15 μg/mL at 12 hours and decreased after 24 hours after feeding. The highest concentration of salbutamol in urine was 15.85±4.42 μg/mL at 18 hours and decreased gradually starting at 24 hours. This result concluded that salbutamol residues mostly excreted in the urine, and the highest salbutamol residues in plasma samples formed faster but also decreased more rapidly than residues formed in urine. The residue formed in plasma is lower than that in the urine.

Development and Validation of Salbutamol, Bromhexine, Ambroxol and Guauaifenesin Determination in Human Plasma by HPLC-MS/MS Method

Introduction. Multicomponent oral drugs containing salbutamol, bromhexine, ambroxol and guaifenesin have a mucolytic, expectorant and bronchodilator effect. The development method for determination substances in biological fluids is a main procedure for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs. There is no published data of the determination of bromhexine, ambroxol and guaifenesin, but there a lot of published methods for divided determination analytes in a biological fluid. This study presents the development and validation of a method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human blood plasma by high performance liquid chromatography with tandem mass spectrometric detection. A sample preparation was perfomed by solid-phase extraction. Deuterated derivatives were used as internal standards.Aim. The aim of the study is to develop a method for the quantitative determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection for performing the analytical part of pharmacokinetic studies.Materials and methods. Determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection. A sample was prepared using solid-phase extraction.Results and discussion. The method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over and stability.Conclusion. The method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma was developed and validated by HPLC-MS/MS. The analytical range of the was 0.1–20 ng/mL in plasma for salbutamol, 0.25–25 ng/mL in plasma for bromhexine, 0.075–3 ng/mL in plasma for ambroxol, and 10–2000 ng/mL in plasma for guaifenesin. Method could be applied to determination of salbutamol, bromhexine, ambroxol and guaifenesin in plasma for PK and BE studies.

Identification of the major metabolites of (R)-salbutamol in human urine, plasma and feces using ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

(R)-Salbutamol is a selective β2-adrenoreceptor agonist, which produces a short-acting bronchodilator effect and is widely used for the treatment of respiratory diseases in humans. Drug metabolism and identification of the metabolites play an essential role in the evaluation of the overall efficacy and safety of the drugs in clinical practices. There are few reports on the identification of major metabolites of (R)-salbutamol in humans, and the number of identified metabolites is very limited. In this research, a method of ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was developed for the discovery and identification of (R)-salbutamol and its major metabolites in human biological samples. Totally, twelve metabolites of (R)-salbutamol were found and identified and all the metabolites could be found in urine, one metabolite in plasma and two metabolites in feces. Among all the metabolites, eight metabolites have never been reported before. The results indicated that (R)-salbutamol was mainly metabolized through isomerization, oxidation, reduction, glucuronidation, and sulfation pathways in vivo. The possible metabolic pathways of (R)-salbutamol were subsequently presented in this study, which contribute to a better understanding of the metabolism of (R)-salbutamol in humans.

The use of hair as a long‐term indicator of low‐dose β2 agonist treatments in cattle: Implications for growth‐promoting purposes monitoring

The objective of this study was to assess the feasibility of using hair as a long-term indicator of cocktail (low-dose β2 agonists) treatments in cattle. Six male Simmental cattle were treated with a mixture of low-dose clenbuterol, ractopamine, and salbutamol at dosages of 5.3, 223.3, and 50.0μg/kg, respectively. The trial lasted for 112days and included 28days of treatment and 84days of withdrawal. Plasma and urine samples taken during the treatment period contained the highest residues, with maximum concentrations of clenbuterol, ractopamine, and salbutamol in plasma of 1.49ng/mL (Day 21), 43.78 (Day 14) ng/mL, and 8.07ng/mL (Day 7), respectively, and in urine of 62.40ng/mL (Day 28), 3995.77ng/mL (Day 28), and 503.72ng/mL (Day 1), respectively. On day 42 of withdrawal, the residues of all three β2 agonists in plasma were below the limit of quantification (LOQ; 0.3ng/mL for clenbuterol, and 0.5ng/mL for ractopamine and salbutamol), and in urine samples were below or near the LOQ (the highest being ractopamine at 1.10ng/mL). The highest concentrations of clenbuterol, ractopamine, and salbutamol in hair were 88.36, 1351.92, and 100.58ng/g, respectively, on day 14 of withdrawal; and the residues were long-lasting, with 7.64, 28.55, and 8.77ng/g, respectively, on day 84 of withdrawal. The results of this study demonstrate that hair could be utilized as a long-term indicator of the use of a combination of low-dose β2 agonists in cattle, which could have implications for growth-promoting purposes monitoring.

Simultaneous determination of salbutamol and clenbuterol in human plasma using liquid chromatography coupled to tandem mass spectrometry

Simultaneous determination of salbutamol and clenbuterol in human plasma using liquid chromatography coupled to tandem mass spectrometry

Simultaneous determination of ambroxol and salbutamol in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry assay method was developed for simultaneous determination of ambroxol and salbutamol in human plasma using citalopram hydrobromide as internal standard (IS). The sample was alkalinized with ammonia water (33:67, v/v) and extracted by single liquid-liquid extraction with ethyl acetate. Separation was achieved on Waters Acquity UPLC BEH C18 column using a gradient program at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 378.9 → 263.6 (ambroxol), m/z 240.2 → 147.7 (salbutamol) and m/z 325.0 → 261.7 (IS). The total analytical run time was relatively short (3 min). Calibration curves were linear in the concentration range of 0.5-100.0 ng/mL for ambroxol and 0.2-20.0 ng/mL for salbutamol, with intra- and inter-run precision (relative standard deviation) <15% and accuracy (relative error) ranging from 97.7 to 112.1% for ambroxol and from 94.5 to 104.1% for salbutamol. The method was successfully applied in a clinical pharmacokinetic study of the compound ambroxol and salbutamol tablets.

Identification of Major Metabolites of Salbutamol in Swine Urine and Plasma Using Ultra-High Performance Liquid Chromatography-Electrospray Time of Flight Mass Spectrometry

The excretion of urinary and plasmic metabolites of salbutamol was studied using ultra performance liquid chromatography electrospray ionization quadrupole time-of-flight tandem mass spectrometry, after a single intragastric gavaged dose administration with salbutamol. The software of Agilent Mass Hunter Metabolite ID was employed to find and identify the chemical structure of metabolites of salbutamol. Five metabolites from salbutamol were identified. The metabolites identified in swine urine included glucuronide conjugate salbutamol, N-oxide-salbutamol, hydroxyl-salbutamol, methoxyl-salbutamol and dehydrated hydroxyl-salbutamol. Whereas, only the parent drugs, glucuronide conjugate salbutamol and N-oxide salbutamol were observed in plasma.

Rapid Immunoassay Method for the Determination of Clenbuterol and Salbutamol in Blood

The aim of the study was to evaluate the adequacy of enzyme-linked immunosorbent assay (ELISA) in the post-exposure determination of the β-agonists clenbuterol and salbutamol in animal plasma and serum. Experimental guinea pigs (n = 20) were treated with two doses (0.25 and 2.5 mg/kg) of clenbuterol (n = 10) and salbutamol (n = 10) for seven days, whereas the control animal group (n = 10) was left untreated. Validation of the applied method yielded acceptable recovery (mean > 70%) and repeatability rates, showing ELISA to be applicable for the semi-quantitative determination of both analytes in both matrices, preferably in plasma. In both matrices, clenbuterol concentrations were proven to be significantly (14-fold) higher than those of salbutamol. Concentrations of both analytes were higher in plasma than in serum. The application of a 10-fold higher clenbuterol and salbutamol dose (2.5 mg/kg) resulted in concentrations 3- to 4-fold higher for clenbuterol and 2- to 3-fold higher for salbutamol, indicating a different release rate of these two β-agonists.

Determination of Salbutamol in Pharmaceutical and Serum Samples by Adsorptive Stripping Voltammetry on a Carbon Paste Electrode Modified by Iron Titanate Nanopowders

AbstractThis study introduces a fast and direct electrochemical method for the determination of salbutamol using an iron titanate nanopowder‐modified carbon paste electrode. The electrochemical behavior of salbutamol was studied by differential pulse adsorptive stripping voltammetry. Factors affecting the performance of the adsorptive stripping such as the modifier percent, the electrolyte pH and accumulation time and potential were optimized. The resulting electrode exhibited a linear response in the range of 0.2–25 nM of salbutamol with a detection limit of 90 pM. The proposed method was successfully applied to determine salbutamol in pharmaceutical formulations and human blood plasma.

High Performance Liquid Chromatographic Method Development and Its Validation for Salbutamol

Aims: A simple and sensitive high performance liquid chromatographic (HPLC) method was developed for quantification of salbutamol in rat plasma. Terbutaline was used as an internal standard (IS). Study Design: Validation study. Methodology: The present method used solid phase extraction of salbutamol from rat plasma. Chromatographic separation achieved isocratically on reversed-phase c18 column (250 × 4.6 mm, 5μ) and the column effluent was monitored by uv detector at 276 nm. The mobile phase used was acetonitrile: 50mm ammonium acetate (ph 7.0), (80: 20 % v/v) at a flow rate of 1.0 ml/min. Results and Discussion: This method was linear over the range of 50.0 – 1000.0 ng/ml with regression coefficient greater than 0.99. Conclusion: The method was found to be precise, accurate and specific during the study. The simplicity of the method allows for application in laboratories that lack sophisticated analytical instruments such as LC–MS/MS or GC–MS/MS that are complicated, costly and time consuming rather than a simple HPLC–UV method. The method was successfully applied for pharmacokinetic study of salbutamol in rats.

High Performance Liquid Chromatographic Method Development and Its Validation for Salbutamol

Aims: A simple and sensitive high performance liquid chromatographic (HPLC) method was developed for quantification of salbutamol in rat plasma. Terbutaline was used as an internal standard (IS). Study Design: Validation study. Methodology: The present method used solid phase extraction of salbutamol from rat plasma. Chromatographic separation achieved isocratically on reversed-phase c18 column (250 × 4.6 mm, 5μ) and the column effluent was monitored by uv detector at 276 nm. The mobile phase used was acetonitrile: 50mm ammonium acetate (ph 7.0), (80: 20 % v/v) at a flow rate of 1.0 ml/min. Results and Discussion: This method was linear over the range of 50.0 – 1000.0 ng/ml with regression coefficient greater than 0.99. Conclusion: The method was found to be precise, accurate and specific during the study. The simplicity of the method allows for application in laboratories that lack sophisticated analytical instruments such as LC–MS/MS or GC–MS/MS that are complicated, costly and time consuming rather than a simple HPLC–UV method. The method was successfully applied for pharmacokinetic study of salbutamol in rats.

Determination of salbutamol in human plasma and urine using liquid chromatography coupled to tandem mass spectrometry and its pharmacokinetic study

A sensitive and selective liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of salbutamol in human plasma and urine, and successfully applied to the pharmacokinetic study of salbutamol in Chinese healthy volunteers after inhalation of salbutamol sulfate aerosol. Salbutamol and the internal standard (IS) acetaminophen in plasma and urine were extracted with ethyl acetate, separated on a C(18) reversed-phase column, eluted with mobile phase of acetonitrile-ammonium acetate (5 m m; 30:70, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor → product ions of m/z 240.2 → 148.1 for salbutamol and 152 → 110 for the IS. The lower limits of quantitation of salbutamol in human plasma and urine by this method were 0.02 and 1 ng/mL, respectively. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision and several stabilities were validated for salbutamol in human plasma and urine. In conclusion, the validation results showed that this method is robust, specific and sensitive, and can successfully fulfill the requirement of clinical pharmacokinetic study of salbutamol in healthy Chinese volunteers.

Simultaneous determination of ipratropium and salbutamol in rat plasma by LC–MS/MS and its application to a pharmacokinetic study

A novel, sensitive and specific LC–MS/MS method with silica-based solid-phase extraction was developed for simultaneous determination of ipratropium (IPR) and salbutamol (SAL) in rat plasma. Chromatographic separation was achieved on a Shiseido Capcell Pak CR column (SCX:C 18 = 1:4, 150 mm × 2.0 mm, 5 μm) with a mobile phase consisting of methanol/water (85:15, v/v) containing 20 mmol/L ammonium formate and 0.1% formic acid at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via multiple reaction monitoring (MRM) under positive ionization mode. This method was validated in terms of specificity, linearity, accuracy (within ±115.4%), intra- and inter-day precision (<11.4%) over the concentration range of 8–1612 pg/mL for IPR and 50–10,000 pg/mL for SAL. In addition, stability and matrix effects of IPR and SAL in plasma were evaluated. This method has been successfully applied to the pharmacokinetic study of compound ipratropium bromide aerosol mainly containing ipratropium bromide (IB) and salbutamol sulphate (SS) after inhalation in rats.

Determination of salbutamol in human plasma and urine by gas chromatography—mass spectrometry

Determination of salbutamol in human plasma and urine by gas chromatography—mass spectrometry

Determinação das concentrações plasmáticas de salbutamol pós-nebulização em serviço de emergência pediátrica

OBJETIVOS: Validar parcialmente a metodologia para determinação do salbutamol em plasma humano por cromatografia líquida de alta eficiência (detecção por fluorescência). Analisar as concentrações plasmáticas de salbutamol em um grupo de pacientes pediátricos com indicação de nebulizações em sala de emergência. MÉTODO: Estudo transversal, analítico, prospectivo, do tipo série de casos. Foram selecionados consecutivamente 15 pacientes com idade entre 12 e 37meses, com diagnóstico de crise aguda de asma, atendidos no Serviço de Emergência Pediátrica do Hospital da Criança Santo Antônio - Complexo Hospitalar Santa Casa, Porto Alegre, Brasil. Os pacientes foram tratados conforme a rotina da unidade para manejo de crise aguda de asma: nebulização (fluxo 6-8 L/min) com salbutamol (0,15 mg/kg) diluídosem4mL de NaCL 0,9%. A nebulização era administrada seqüencialmente, em intervalos de 20 minutos, por três vezes. Concomitantemente às nebulizações, todos os pacientes recebiam prednisolona via oral (1 mg/kg). RESULTADOS: As concentrações plasmáticas evidenciaram grande variabilidade em portadores de crise aguda de asma que receberam três nebulizações com salbutamol (0,15 mg/kg). Níveis plasmáticos médios foram de 12,09±10,8 ng/mL, com mediana de 8,9 (IQ25-75% 2,75-17,65) e coeficiente de variação da amostra de 92,4%. CONCLUSÕES: As concentrações plasmáticas após inalação de salbutamol apresentam grande dispersão na população pediátrica, a exemplo de outros estudos. As possíveis causas e implicações relacionadas ao achado permanecem alvo de controvérsias e avaliações complementares.

Determination of plasma salbutamol concentrations after nebulization in a pediatric emergency department

To partially validate the methodology for determining salbutamol in human plasma through high-efficiency liquid chromatography and fluorescence detection. To analyze plasma salbutamol concentrations in a group of pediatric patients with indication for nebulization in the emergency room. Analytical, prospective cross-sectional case series. Fifteen patients aged 12 to 37 months with a diagnosis of acute asthma crisis were selected at the Pediatric Emergency Service at Hospital da Criança Santo Antônio - Complexo Hospitalar Santa Casa, Porto Alegre, Brazil. The patients were treated following the unit's routine for the management of acute asthma crises: nebulization with salbutamol (flow rate of 6-8 L/min) (0.15 mg/kg) suspended in 4 mL of 0.9% saline solution. Nebulization was administered sequentially, three times, at 20 minute intervals. All patients were given prednisolone orally (1 mg/kg) concurrently with the nebulizations. Plasma concentrations exhibited great variability in acute asthma crisis patients given three nebulizations of salbutamol (0.15 mg/kg). The mean level in plasma was 12.09 +/- 10.8 ng/mL, with a median of 8.9 ng/mL (IQ25-75% 2.75-17.65). The sample's coefficient of variation was 92.4%. Post-inhalation plasma salbutamol concentrations exhibit great variation in the pediatric population, as seen in other studies. The possible causes and implications of this finding remain the subject of disagreements and of further assessments.

Fast determination of salbutamol, abused by athletes for doping, in pharmaceuticals and human biological fluids by square wave voltammetry

The determination of salbutamol, used for doping, has been carried out at nano gold particles modified indium tin oxide (NGITO) electrode using Osteryoung square wave voltammetry. The NGITO electrode exhibited an effective catalytic response towards salbutamol oxidation as compared to bare ITO and bulk gold electrodes. The peak current was also found to be significantly increased. The determination was carried out in phosphate containing electrolyte in the pH range 4.0–10.0 and two well-defined peaks were noticed. The first peak was found to be linearly dependent on concentration of salbutamol in the concentration range 50–2000 ng/ml with a detection limit of 75 ng/ml, whereas the second peak was due to adsorption of product. The product of oxidation corresponding to first peak was found to be C–C linked dimer and peak II was due to strong adsorption of dimer. The proposed method has been applied to determine the concentration of salbutamol in pharmaceutical formulations and human blood plasma and urine samples. A comparison of salbutamol concentration determined by proposed method and GC–MS indicated a good agreement. It is believed that the method is simple, rapid and can be easily used in determining this drug in case of its abuse in doping.

Determination of salbutamol in human plasma and urine by high-performance liquid chromatography with a coulometric electrode array system.

A method is developed to determine salbutamol in human plasma and urine using high-performance liquid chromatography (HPLC) with a coulometric electrode array system, based on the electrochemical behavior of salbutamol at graphite electrode. The mobile phase component A is 30 mM sodium dihydroxy phosphate-30 mM triethylamine and is adjusted to pH 6.0 with 20% phosphate acid. The mobile phase component B is methanol. The optimized mobile phase composition was A and B in the proportion of 90:10 (v/v). Paracetamol is selected as the external standard. The human plasma and urine samples are pretreated using solid-phase extraction cartridges (Sep-Pak Silica), and the eluting solution is monitored by the coulometric electrode array system. The electrode potentials are set at 300, 400, 550, and 650 mV, respectively. Calibration curves show good linearity, and the recovery of salbutamol proves to be constant and unaffected by the concentration of the drug. This method, developed using HPLC-electrochemical detection, is reproducible and sensitive enough for the determination of salbutamol in human plasma and urine.