One year monitoring of potency change in commercial ibuprofen products stored in a household setting exposed to normal day-to-day temperature and humidity fluctuations
Location
Ballroom
Start Date
4-12-2019 9:00 AM
End Date
4-12-2019 2:30 PM
Poster Number
41
Faculty Sponsor’s Department
Pharmaceutical Sciences
Name of Project's Faculty Sponsor
Dr. Stacy Brown
Type
Poster: Competitive
Project's Category
Chromatography, Mass Spectrometry, Chemical Effects, Safety
Abstract or Artist's Statement
Introduction.Most over the counter (OTC) medications are labeled for storage in a room temperature environment (68 – 77oF) under dry conditions, i.e. kept away from moisture. Despite this, many households store medications in the bathroom, where both temperature and humidity extremes may be experienced during the course of the day. In this project, we sought to investigate the effect that long-term storage in a household bathroom had on potency of OTC ibuprofen (IBU) products. One degradation product, 4-isobutylacetophenone (4-IBP), has been shown to possess toxic properties. As such, the emergence of this breakdown product was also monitored.
Methods. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the quantitative determination of IBU and 4-IBP in aqueous samples. The assay utilized a UCT C18 column (2.1 x 100 mm; 1.8 micron) with acetonitrile as the organic phase and water as the aqueous phase, run in isocratic mode (15% A: 85% B). Ibuprofen was ionized in negative electrospray mode (-ESI) using m/z 205.09 and 4-IBU in +ESI mode at m/z 177.15. Calibration curves were created in the ranges of 0.1 – 2 mg/mL (IBU) and 2 – 100 mg/mL. Three brands each of IBU tablets (200mg) and suspensions (100mg/5mL) were purchased and assayed for IBU concentration at the initiation of the study. The samples were stored in a household bathroom, while temperature and humidity were continuously recorded using Extech Instruments RHT10 data-logger. Three tablets were removed from each bottle, and three 5-mL aliquots were removed from each suspension, for analysis each month. The samples were digested in 0.1M HCl for 1hr using sonication, and diluted to assay concentration (2 mg/mL for tablets; 0.2 mg/mL for suspensions) using acetonitrile. Each sample was assayed in triplicate and percent recovery was calculated against freshly prepared standards of IBU.
Results. Acceptable potency range was defined as 90 – 110% of the labeled concentration. All tablets maintained acceptable average strength through three months, and a statistically significant change from initial concentration (as determined by a 2-way ANOVA, p = 0.05) was detected after 6 – 7 months. After ten months of storage, the average tablet strength was 74% of initial potency. All suspensions maintained acceptable average strength through five months, with statistically significant changes from initial concentration emerging after seven months storage. After 10 months of storage, the average suspension strength was 84% of initial potency. During the duration of the study, the average storage temperature was (20.9° C) and the average relative humidity was (65.7). The 4-IBU was not detected in any of the product samples during the duration of the study.
Conclusions.These data indicate that, while the toxic degradation product, 4-IBU, has not been detected following bathroom storage of commercial IBU products, significant changes in product potency can negatively affect product efficacy. The container-closure systems used in OTC ibuprofen products do not protect against the effects of ongoing fluctuations in environmental temperature and humidity. Data indicate that suspension products are more resistant to temperature and humidity fluctuations, at least to the degree that would be present in a household bathroom.
One year monitoring of potency change in commercial ibuprofen products stored in a household setting exposed to normal day-to-day temperature and humidity fluctuations
Ballroom
Introduction.Most over the counter (OTC) medications are labeled for storage in a room temperature environment (68 – 77oF) under dry conditions, i.e. kept away from moisture. Despite this, many households store medications in the bathroom, where both temperature and humidity extremes may be experienced during the course of the day. In this project, we sought to investigate the effect that long-term storage in a household bathroom had on potency of OTC ibuprofen (IBU) products. One degradation product, 4-isobutylacetophenone (4-IBP), has been shown to possess toxic properties. As such, the emergence of this breakdown product was also monitored.
Methods. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the quantitative determination of IBU and 4-IBP in aqueous samples. The assay utilized a UCT C18 column (2.1 x 100 mm; 1.8 micron) with acetonitrile as the organic phase and water as the aqueous phase, run in isocratic mode (15% A: 85% B). Ibuprofen was ionized in negative electrospray mode (-ESI) using m/z 205.09 and 4-IBU in +ESI mode at m/z 177.15. Calibration curves were created in the ranges of 0.1 – 2 mg/mL (IBU) and 2 – 100 mg/mL. Three brands each of IBU tablets (200mg) and suspensions (100mg/5mL) were purchased and assayed for IBU concentration at the initiation of the study. The samples were stored in a household bathroom, while temperature and humidity were continuously recorded using Extech Instruments RHT10 data-logger. Three tablets were removed from each bottle, and three 5-mL aliquots were removed from each suspension, for analysis each month. The samples were digested in 0.1M HCl for 1hr using sonication, and diluted to assay concentration (2 mg/mL for tablets; 0.2 mg/mL for suspensions) using acetonitrile. Each sample was assayed in triplicate and percent recovery was calculated against freshly prepared standards of IBU.
Results. Acceptable potency range was defined as 90 – 110% of the labeled concentration. All tablets maintained acceptable average strength through three months, and a statistically significant change from initial concentration (as determined by a 2-way ANOVA, p = 0.05) was detected after 6 – 7 months. After ten months of storage, the average tablet strength was 74% of initial potency. All suspensions maintained acceptable average strength through five months, with statistically significant changes from initial concentration emerging after seven months storage. After 10 months of storage, the average suspension strength was 84% of initial potency. During the duration of the study, the average storage temperature was (20.9° C) and the average relative humidity was (65.7). The 4-IBU was not detected in any of the product samples during the duration of the study.
Conclusions.These data indicate that, while the toxic degradation product, 4-IBU, has not been detected following bathroom storage of commercial IBU products, significant changes in product potency can negatively affect product efficacy. The container-closure systems used in OTC ibuprofen products do not protect against the effects of ongoing fluctuations in environmental temperature and humidity. Data indicate that suspension products are more resistant to temperature and humidity fluctuations, at least to the degree that would be present in a household bathroom.