Development and validation of a UPLC-ESI-MS/MS method for the determination of N-butylscopolamine in human plasma: Application to a bioequivalence study

作者：Jann Favreto Wagner Alex; Pugens Pinto Ana Maria; Manfio Joselia Larger; Fiametti Karina Graziella; Percio Maycon Fernando; dos Santos Mauricio Bedim

来源：Drug Testing and Analysis, 2012, 4(3-4): 215-221.

DOI：10.1002/dta.403

• N-butylscopolamine
• UPLC-ESI-MS
• MS
• plasma
• protein precipitation
• bioequivalence

A sensitive and fast ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method for measurements of N-butylscopolamine in plasma was developed and validated. A single protein precipitation was proposed for the clean up of the plasma and N-methylhomatropine was added as internal standard (IS). The analyses were carried out using a C18 column and mobile phase of acetonitrile: 5?mM ammonium acetate?+?0.1% formic acid (90:10, v/v). The triple quadrupole mass spectrometer equipped with an electrospray source in positive mode, was set up in selective reaction monitoring, to detect precursor???product ion 360.0???194.0?m/z and 290.3???138.0?m/z transitions, for N-butylscopolamine and IS, respectively. The method was linear in 0.03 (lower limit of quantitation; LLOQ) 10.00?ng/ml range for N-butylscopolamine. Satisfactory selectivity, linearity, precision, accuracy, and robustness were obtained for the UPLC-ESI-MS/MS method. The proposed method was successfully applied to a pharmacokinetic study of healthy human volunteers; the results showed that the two scopolamine butylbromide formulations tested are not bioequivalent in rate and extent of absorption.

• 出版日期2012-4