Quantitative 1H-NMR became an increasingly important issue in pharmaceutical analytical chemistry. This study used NMR spectroscopy to assay the bronchodilator drug terbutaline sulfate and its pro-drug bambuterol hydrochloride in pure form and pharmaceutical preparations. The technique proceeded using deuterium oxide (D2O) as an 1H-NMR solvent and phloroglucinol anhydrous as an internal standard (IS). Comparatively, to the phloroglucinol signal at 5.9 ppm, the resulting quantitative signals of the studied drugs were corrected. The terbutaline singlet signal at 6.3 ppm was chosen for quantification, while the bambuterol quantitative singlet signal was at 2.9 ppm. The two drugs were rectilinear over the concentration range of 1.0-16.0 mg/mL. LOD values were 0.19 and 0.21 mg/mL while LOQ values were 0.58 and 0.64 mg/mL for terbutaline and bambuterol respectively. The developed method has been validated according to the International Conference of Harmonization (ICH) regarding linearity, accuracy, precision, specificity, and robustness. A greenness profile assessment was applied, and the method proved to be green. The method enables the assay of the two drugs in pure drug and pharmaceutical preparations. The method also enables the assay of the two drugs in the presence of each other; thus, it is considered a stability-indicating method where terbutaline is an acid degradation product of bambuterol.

Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer\'s disease. In this work, one rivastigmine-bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC50(AChE) > 100,000 nM, IC50(BChE) = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood-brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer\'s disease.

Silver nanoparticles (AgNPs) were found to significantly quench the fluorescence of bambuterol hydrochloride (BAM) and its active metabolite terbutaline sulfate (TER). The intrinsic fluorescence intensity of each of BAM (at 264/292 nm) and TER (at 276/306 nm) decreased by the gradual addition of AgNPs. Quenching of the steady state fluorescence of BAM and TER probably resulted from the energy transfer to the photo-excited state of AgNPs. The estimated Stern-Volmer quenching constant at several temperature settings proved that the quenching mechanism of the two drugs was dynamic quenching in case of BAM while it was static quenching in case of TER. The number of binding sites, binding constants, and corresponding thermodynamic parameters depending on the interaction system were estimated at 293, 313, and 333 °K and the results obtained were interpreted.

Sensitive, simple and green analytical methodology for simultaneous estimation of bambuterol and montelukast as a combined medication based on their native fluorescence character was developed. The method relies on synchronous spectrofluorimetry to solve the problem of the overlapping emission spectra of the studied drugs. Using second derivative synchronous spectra enabled the simultaneous quantitation of bambuterol and montelukast without interference. The peak amplitudes of the aqueous solutions at Δλ = 20 nm were estimated at 284 and 304 nm for bambuterol and at 374 and 384 nm for montelukast. A linear relationship was achieved over the concentration range of 0.2-1.00 µg ml-1 for bambuterol and 0.4-2.00 µg ml-1 for montelukast. All factors and parameters were carefully studied to obtain the highest sensitivity and good precision of the proposed method. Additionally, the validation criteria were assessed in accordance with International Council of Harmonization (ICH) guidelines. The method was used for the estimation of both drugs in their raw materials, synthetic mixtures as well their combined tablets with good agreement between its results and those from the comparison method.

A green, sensitive and cost-effective method is introduced in this research for the determination of bambuterol and its main degradation product, terbutaline, simultaneously, relying on the synchronous spectrofluorimetric technique. First derivative synchronous spectrofluorimetric amplitude is measured at Δλ = 20 nm, so bambuterol can be quantitated at 260 nm, and terbutaline can be measured at 290 nm, each at the zero crossing point of the other. The amplitude-concentration plots were linear over the concentration ranges of 0.2-6.0 µg ml-1 and 0.2-4.0 µg ml-1 for both bambuterol and terbutaline, respectively. Official guidelines were followed to calculate the validation parameters of the proposed method. The low values of limits of detection of 0.023, 0.056 µg ml-1 and limits of quantitation of 0.071, 0.169 µg ml-1 for bambuterol and terbutaline, respectively, point to the sensitivity of the method. Bambuterol is a prodrug for terbutaline, and the latter is considered its degradation product so the established method could be regarded as a stability-indicating one. Moreover, the proposed method was used for the analysis of bambuterol and terbutaline in their single ingredient preparations and the results revealed statistical agreement with the reference method. The suggested method, being a simple and low-cost procedure, is superior to the previously published methods which need more sophisticated techniques, longer analysis time and highly toxic solvents and reagents. It could be considered as an eco-friendly analytical procedure.

Bambuterol (BAM) and terbultaline (TER) are well known and effective bronchodilators. In this article highly sensitive, green and cost-effective spectrofluorimetric methods are designed to determine low concentrations of such drugs. The proposed methods are based on an investigation of the native fluorescence properties of aqueous solutions of BAM at 298 nm after excitation at 263 nm and of TER at 313 nm after excitation at 275 nm. Under optimum conditions, the plots of the relative fluorescence intensity versus concentration were rectilinear over the range 0.1-1.2 μg/mL for BAM and 0.05-0.5 μg/mL for TER with a limit of quantitation of 0.067 μg/mL for BAM and 0.018 μg/mL for TER. The methods are simple and hence suitable for application to the quantification of BAM and TER in syrups and tablets without interference from common excipients. Furthermore, based on United States Pharmacopeia (USP) guidelines, the application was extended to determine the content uniformity of the cited drugs in low dose tablets. The developed methods were fully validated according to the guidelines of the International Conference on Harmonization (ICH).

We have described a continuous flow ATR-FTIR method for measuring some of the Butyrylcholinesterase enzyme kinetics (Km and Vmax). This is done by developing a circulating system to be close as much as possible to the human circulation using human serum as a source of the enzyme with adjusted pH, isotonicity and temperature to give the maximum affinity of the enzyme towards its substrate (bambuterol). The experiment was running continuously for 90 min to monitor the production of terbutaline from the zero time of its appearance with a measured spectrum in each minute using ZnSe prism. The method was selective and successful for determination of Vmax to be 8.16 × 10-8 mol/min/ml and Km to be 2.28 × 10-5 mol, showing high affinity of the enzyme towards its prodrug substrate Bambuterol. This study critically probes the quantitative ability of the ATR-FTIR method for terbutaline, which was validated according to ICH guidelines showing high accuracy 100.39% and high selectivity towards the produced terbutaline, as the produced spectrums considered as fingerprint of each compound.

In this study, an enantioselective analytical method based on microwave-assisted chiral derivatization coupled with ultra high performance liquid chromatography and tandem mass spectrometry was developed for the determination of bambuterol enantiomers in human plasma. The chiral derivatization reaction was greatly accelerated by microwave irradiation. Under the optimized conditions, both the derivatization time and separation time on column was only 3 min, and the lower limit of quantification was 2.5 pg/mL. The recoveries were in the range of 90.1-93.0% without significant matrix effect. Compared with the conventional heating chiral derivatization, microwave-assisted chiral derivatization obtained higher chiral derivatization yields with much shorter time due to the effect of microwave irradiation. Furthermore, the racemization during the derivatization reaction was systematically investigated. The results showed the concentration of acetic acid and the reaction time had significant effects on the racemization, which could be well controlled during microwave-assisted chiral derivatization for the short reaction time. Finally, this novel approach was demonstrated by determining bambuterol in human plasma of a clinical pharmacokinetic study in eight healthy volunteers. On the basis of the results, microwave-assisted chiral derivatization coupled with ultra high performance liquid chromatography and tandem mass spectrometry as a simple and effective enantioselective analysis technique for the determination of chiral drugs in complex biological samples showed great promise.

An increase activity of butyrylcholinesterase is believed to contribute to Alzheimer\'s disease. Bambuterol is a known potent inhibitor of butyrylcholinesterase, but it has undesired cardiac effects and less lipophilicity. Thirteen bambuterol analogues were synthesized using 1-(3, 5-dihydroxyphenyl) ethanone as a starting material. In-vitro cholinesterase assay established that the majority of the compounds are specific butyrylcholinesterase inhibitors. Out of the 13 compounds, two bambuterol derivatives, BD-6 and BD-11 exhibited similar efficacies in inhibiting butyrylcholinesterase with fewer effects on heart and enhanced possibilities of permeating through the blood-brain barrier as compared to bambuterol. These bambuterol analogues may provide better alternatives for treatments of Alzheimer\'s disease.

(R)-Bambuterol, a selective β2-adrenoceptor agonist, has been approved as a new drug for the treatment of asthma and chronic obstructive pulmonary disease by the China Food and Drug Administration and is currently under phase I clinical trials. In this study, a combined method based on ultra high performance liquid chromatography with triple quadrupole mass spectrometry and ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was employed for the identification of the major metabolites of (R)-bambuterol in human plasma and urine after an oral dose of 10 mg. The metabolites were separated by gradient elution program and different sample preparation methods were compared. Totally, 12 metabolites of (R)-bambuterol were identified, including four metabolites in plasma and all 12 metabolites in urine. Among these, four metabolites are reported for the first time. The possible metabolic pathways of (R)-bambuterol were subsequently proposed. The results indicated that (R)-bambuterol was metabolized via hydrolysis, demethylation, oxygenation, glucuronidation, and sulfation pathways in vivo. This study revealed that this combined method was accurate and sensitive to identify the possible metabolites and to better understand the metabolism of (R)-bambuterol in vivo.