Quantitation of Solifenacin in Human Plasma using a Specific and Sensitive Liquid Chromatography-Tandem Mass Spectrometry Technique

Purpose: The current work validated a high performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) bioassay method developed in-house for the quantitation of solifenacin in human plasma.Methods: Solifenacin was extracted from plasma by a liquid-liquid extraction (LLE) technique using tertbutyl methyl ether. The dry extract was then reconstituted with 200 μL of the mobile phase (acetonitrilewater (80:20, v/v)). Solifenacin-d5 was the internal standard (IS). Elution was carried out on a C18 column at a flow rate of 1 mL/min. The MS/MS employed turbo-ion spray ionization in the positive ion mode. Solifenacin and IS were monitored at a mass to charge ratio (m/z) of 363.4 and 368.4, respectively. Bioassay validation followed International Bioanalytical Method Validation Guidelines.Results: The validated calibration curves were linear over a range of 0.5 – 60.0 ng/mL (regression factors ≥ 0.9994). Method specificity was established in 6 different human plasma batches. Intra- and inter-day precision and accuracy were within ± 20 % (for lower limit of quantitation (LLOQ)) and ± 15 % (for low, mid and high quality control (QC) levels). Short- and long-term stability was within accepted range.Conclusion: A specific, accurate and precise HPLC-MS/MS method has been validated for the determination of solifenacin in human plasma.Keywords: Liquid extraction, Mass spectrometry, Solifenacin, Validatio

Education on Correct Inhaler Technique in Pharmacy Schools: Barriers and Needs

Purpose: To investigate the effectiveness of a standard educational module on pharmacy students’ inhaler technique demonstration skills.Methods: This investigational study was conducted during the Clinical Pharmacy and Therapeutics tutorial classes in 2011. All fifth-year students were given placebo inhaler devices and information leaflets explaining the use of these devices. Students were then shown, by demonstration, the correct technique for each of the inhalers. All the students were assessed on the use of each of the inhalers two weeks following the tutorial. A validated questionnaire regarding the students’ barriers to demonstrate the correct inhaler technique was completed by all the students. The inhaler techniques  emonstratedwere Accuhaler (ACC), Turbuhaler (TH) and metered-dose inhaler (MDI).Results: Students scored significantly better with ACC with a score of 4.38 ± 1.81 (out of 9.00) than with TH (3.96 ± 1.75 out of 9.00); p = 0.004, and MDI (2.69 ± 1.76 out of 8.00); p < 0.001, based on Friedman test 2 weeks following training. The majority of students (78 %) believed that lack of practice with the devices was the primary barrier to correct inhaler use.Conclusion: Standard educational training may not be the most appropriate method of teaching students the correct use of inhalers. Clearly, there is a practice element missing which needs to be addressed in a feasible way.Keywords: Inhaler technique, Pharmacy education, Hands-on training, Training barrie

Objective Assessment of Patient Inhaler User Technique Using an Audio-Based Classification Approach

Abstract Many patients make critical user technique errors when using pressurised metered dose inhalers (pMDIs) which reduce the clinical efficacy of respiratory medication. Such critical errors include poor actuation coordination (poor timing of medication release during inhalation) and inhaling too fast (peak inspiratory flow rate over 90 L/min). Here, we present a novel audio-based method that objectively assesses patient pMDI user technique. The Inhaler Compliance Assessment device was employed to record inhaler audio signals from 62 respiratory patients as they used a pMDI with an In-Check Flo-Tone device attached to the inhaler mouthpiece. Using a quadratic discriminant analysis approach, the audio-based method generated a total frame-by-frame accuracy of 88.2% in classifying sound events (actuation, inhalation and exhalation). The audio-based method estimated the peak inspiratory flow rate and volume of inhalations with an accuracy of 88.2% and 83.94% respectively. It was detected that 89% of patients made at least one critical user technique error even after tuition from an expert clinical reviewer. This method provides a more clinically accurate assessment of patient inhaler user technique than standard checklist methods