Stacy D. Brown

Active-Learning Processes Used in US Pharmacy Education

Objective. To document the type and extent of active-learning techniques used in US colleges and schools of pharmacy as well as factors associated with use of these techniques. Methods. A survey instrument was developed to assess whether and to what extent active learning was used by faculty members of US colleges and schools of pharmacy. This survey instrument was distributed via the American Association of Colleges of Pharmacy (AACP) mailing list. Results. Ninety-five percent (114) of all US colleges and schools of pharmacy were represented with at least 1 survey among the 1179 responses received. Eighty-seven percent of respondents used active-learning techniques in their classroom activities. The heavier the teaching workload the more active-learning strategies were used. Other factors correlated with higher use of active-learning strategies included younger faculty member age (inverse relationship), lower faculty member rank (inverse relationship), and departments that focused on practice, clinical and social, behavioral, and/or administrative sciences. Conclusions. Active learning has been embraced by pharmacy educators and is used to some extent by the majority of US colleges and schools of pharmacy. Future research should focus on how active-learning methods can be used most effectively within pharmacy education, how it can gain even broader acceptance throughout the academy, and how the effect of active learning on programmatic outcomes can be better documented.

A process-oriented guided inquiry approach to teaching medicinal chemistry.

Objective. To integrate process-oriented guided-inquiry learning (POGIL) team-based activities into a 1-semester medicinal chemistry course for doctor of pharmacy (PharmD) students and determine the outcomes. Design. Students in the fall 2007 section of the Medicinal Chemistry course were taught in a traditional teacher-centered manner, with the majority of class time spent on lectures and a few practice question sets. Students in the fall 2008 and fall 2009 sections of Medicinal Chemistry spent approximately 40% of class time in structured self-selected teams where they worked through guided-inquiry exercises to supplement the lecture material. Assessment. The mean examination score of students in the guided-inquiry sections (fall 2008 and fall 2009) was almost 3 percentage points higher than that of students in the fall 2007 class (P < 0.05). Furthermore, the grade distribution shifted from a B-C centered distribution (fall 2007 class) to an A-B centered distribution (fall 2008 and fall 2009 classes). Conclusions. The inclusion of the POGIL style team-based learning exercises improved grade outcomes for the students, encouraged active engagement with the material during class time, provided immediate feedback to the instructor regarding student-knowledge deficiencies, and created a classroom environment that was well received by students.

Potential Toxicity of Caffeine when Used as a Dietary Supplement for Weight Loss

ABSTRACT Background: Caffeine is added to dietary supplements to increase energy and suppress appetite. Many people take dietary supplements for weight loss. Patients may be unaware that supplements can contain caffeine, even if caffeine is not listed as an ingredient. Commonly used herbal dietary supplement ingredients, such as guarana, are natural sources of caffeine. Objective: To describe a case of possible caffeine-induced seizure in a patient taking an over-the-counter weight loss supplement. Case Report: A previously healthy 38-year-old female experienced blurring of vision and a new onset grand mal seizure. The patient had a two-month history of taking the dietary supplement, Zantrex - 3™. Zantrex - 3™ is advertised as a weight loss supplement which may provide rapid weight loss and extreme energy in one “power packed pill.” Conclusions/Summary: After discontinuation of Zantrex - 3™, the patient experienced no further seizure activity. Outpatient follow up at 2 and 6 weeks was noncontributory with follow up MRI and EEG both within normal limits.

A case-based toxicology elective course to enhance student learning in pharmacotherapy.

Objective. To assess the impact of a case-based toxicology elective course on student learning in related required courses and student performance on the Pharmacy Curriculum Outcomes Assessment (PCOA) examination. Design. A case-based clinical toxicology elective course that contained topics from 2 required courses, Pharmacology III and Pharmacotherapy II, was offered in the spring 2009 to second- and third-year pharmacy students. Assessment. Scores on the Toxicology subsection of the PCOA of students enrolled in the elective were higher than those of students not enrolled (91.3% ± 4.1 vs. 67.2% ± 5.7). Enrollment in the elective was related to increased examination scores among Pharmacotherapy II students (89.5% ± 2.0 vs. 83.9% ± 1.8). Students indicated on course survey instruments that they were satisfied with the new elective offering. Conclusions. A toxicology elective provided a clinically relevant, active-learning experience for pharmacy students that addressed a curricular need within the college and increased examination scores.

The impact of phospholipids and phospholipid removal on bioanalytical method performance

Phospholipids (PLs) are a component of cellmembranes, biological fluids and tissues. These compounds are problematic for the bioanalytical chemist, especially when PLs are not the analytes of interest. PL interference with bioanalysis highly impacts reverse-phase chromatographic methods coupled with mass spectrometric detection. Phospholipids are strongly retained on hydrophobic columns, and can cause significant ionization suppression in the mass spectrometer, as they outcompete analyte molecules for ionization. Strategies for improving analyte detection in the presence of PLs are reviewed, including in-analysis modifications and sample preparation strategies. Removal of interfering PLs prior to analysis seems to be most effective atmoderating thematrix effects fromthese endogenous cellular components, and has the potential to simplify chromatography and improve column lifetime. Products targeted at PL removal for sample pre-treatment, as well as products that combine multiplemodes of sample preparation (i.e. Hybrid SPE), show significant promise inmediating the effect on PL interference in bioanalysis.

Quantification and validation of HPLC-UV and LC-MS assays for therapeutic drug monitoring of ertapenem in human plasma.

Rapid and simple HPLC-UV and LC-MS methods were developed and validated for the quantification of ertapenem (Invanz™) in human plasma. Ertapenem is a unique drug in that current dosing recommendations call for a 1 g dose for normal renal function patients, despite body weight. These assays, which involve a protein precipitation followed by liquid-liquid extraction, allow for fast therapeutic drug monitoring of ertapenem in patients, which is especially useful in special populations. Both methods were sufficient to baseline resolve meropenem (internal standard) and ertapenem, and were validated over 3 days using a six-point calibration curve (0.5-50 µg/mL). Validation was collected using four different points on the calibrations curve yielding acceptable precision (<15% inter-day and intra-day; <20% for lower limit of quantitation, LLOQ) as well as accuracy (<15% inter-day and intra-day; <20% for LLOQ). The lower limit of detection (LOD) was determined to be 0.1 and 0.05 µg/mL for the HPLC-UV and LC-MS methods, respectively. The developed HPLC-UV and LC-MS methods for ertapenem quantification are fast, accurate and reproducible over the calibration range and can be used to determine ertapenem plasma concentrations for monitoring clinical efficacy.

The Fate of Sulfamethazine in Sodium-Hypochlorite-Treated Drinking Water: Monitoring by LC-MS (n) -IT-TOF.

Pharmaceutical compounds represent a rapidly emerging class of environmental contaminants. Such compounds were recently classified by the U.S. Geological Survey, including several antibiotics. An LC-MS/MS screening method for the top five antibiotics in drinking water was developed and validated using a Shimadzu LC-MS-IT-TOF. The separation was performed using a Waters Acquity UPLC BEH C18 column with a gradient elution. Sulfamethazine was exposed to conditions intended to mimic drinking water chlorination, and samples were collected and quenched with excess sodium sulfite. Kinetics of sulfamethazine degradation was followed as well as the formation of the major chlorinated byproduct (m/z 313). For the screening method, all five antibiotic peaks were baseline resolved within 5 minutes. Additionally, precision and accuracy of the screening method were less than 15%. Degradation of sulfamethazine upon exposure to drinking water chlorination occurred by first order kinetics with a half-life of 5.3 × 104 min (approximately 37 days) with measurements starting 5 minutes after chlorination. Likewise, the formation of the major chlorinated product occurred by first order kinetics with a rate constant of 2.0 × 10−2. The proposed identification of the chlorinated product was 4-amino-(5-chloro-4,6-dimethyl-2-pyrimidinyl)-benzenesulfonamide (C12H13N4O2SCl) using MSn spectra and databases searches of SciFinder and ChemSpider.

Quantification of Lansoprazole in Oral Suspension by Ultra-High-Performance Liquid Chromatography Hybrid Ion-Trap Time-of-Flight Mass Spectrometry

An LC-MS/MS method was developed and validated to be used as a stability indicating assay for the study of a 3 mg/mL lansoprazole oral suspension. The method utilizes a UPLC (ultra-performance liquid chromatography) column and unique mass spectrometric detection (ion-trap time-of-flight (IT-TOF)) to achieve a sensitive (LOD 2 ng/mL), accurate, and reproducible quantification of lansoprazole. This method reports an intraday and interday coefficient of variation of 2.98 ± 2.17% (n = 5 for each concentration for each day) and 3.07 ± 0.89% (n = 20 for each concentration), respectively. Calibration curves (5–25 μg/mL) were found to be linear with an R2 value ranging from 0.9972 to 0.9991 on 4 different days. Accuracy of the assay, expressed as % error, ranged from 0.30 to 5.22%. This method is useful for monitoring the stability of lansoprazole in oral suspension.

UHPLC-MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma

Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC-MS/MS method using solid-phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were <15% for each validated concentration. Our data establishes a 2 week maximum freezer storage window in order to achieve the most accurate cord plasma concentrations of these analytes. Additionally, we found that the umbilical cord tissue analysis was less sensitive compared with analysis with umbilical cord blood plasma, indicating that this may be a more appropriate matrix for determination of buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy.

Comparison of three generic vancomycin products using liquid chromatography–mass spectrometry and an online tool

PURPOSE Three different generic vancomycin products were compared using liquid chromatography-mass spectrometry (LC-MS) and open-access metabolomic tools. METHODS Single-lot samples of vancomycin hydrochloride from three different manufacturers (Hospira, APP Pharmaceuticals, and Pfizer) were reconstituted and injected into a high-resolution LC-MS system. The mass spectral fingerprints were compared for similarity of nonvancomycin B components using the XCMS Online system through Scripps University. Significance was defined as a p of ≤0.01 and a fold change of ≥1.5. The concentration of vancomycin B in each product was also measured using LC-MS on days 0, 1, 2, 4, 7, 10, and 14. RESULTS Qualitative comparisons of the products using the XCMS Online interface indicated the presence of significant differences among the products at the time of reconstitution; however, these variations seemed to converge after 14 days of storage. The concentration profiles of vancomycin B during refrigerated storage did not differ significantly among the three products. XCMS Online analyses revealed that the Pfizer and Hospira products were the most similar to each other. CONCLUSION While there were no significant differences found in the concentration of vancomycin B among Pfizer, APP, and Hospira products, there were differences in their initial mass spectral analysis after reconstitution. Liquid chromatography-tandem mass spectrometry profiles of the ions or isotopes present in the three products showed significant differences in impurities such as crystalline degradation product (CDP)-1 and CDP intermediate. After 14 days of refrigerated storage, the differences among the products converged, and fewer distinct features could be detected.