This study examined the photodegradation of the pharmaceutical ranitidine when exposed to solar light in various concentrations of humic acid solutions. Ranitidine degraded more quickly with higher humic acid concentrations, with half-lives ranging from 95 minutes in pure water to 7 minutes in a 20 ppm humic acid solution. High performance liquid chromatography and mass spectrometry identified potential photodegradation products and helped determine degradation rates. Future work will further characterize degradation products through additional analysis.

1. Photodegradation of Ranitidine
Louis Terry, Dr. Wendy Cory
Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424
Abstract Results
Future work will include further identification of potential photodegradants of RAN.
Further qualitative analysis using the LC-MS is also needed to concretely identify the
products of degradation. Once all of the degradation products have been identified, MS/
MS will be used to confirm the identity and structure for products of degradation.
Conclusions
Future Work
We would like to thank the following for supporting our research:
• The Department of Chemistry and Biochemistry
• Summer Undergraduate Research with Faculty (SURF) grant
• The National Science Foundation for the purchase of the UHPLC-ESI-MS
This material is based upon work supported by the National Science Foundation
under CHE-0821426 and NSF-RUI grant CBET-1236266
We would like to thank the following for their help:
• Logan Herbert
• Adam Jenkins
• Jessica Ramirez
• Aliya Dumas
• Sam Elcik
Experimental Methods
To effectively resemble the natural water conditions, we added various
concentrations of humic acid. HA is a complex acid that is naturally
abundant in the environment. The HA acted as the biodegradant of
dead organic matter that is found in surrounding leaves, soil, and
water.
Solutions of 1 ppm RAN with no HA, 1 ppm RAN with 1 ppm HA, 1
ppm RAN with 10 ppm HA, and 1 ppm RAN with 20 ppm HA were
prepared for photoexposure in the solar simulator at 40,000 lx to
replicate natural solar conditions. These aqueous samples placed in
quartz vials were photoexposed at different durations to accurately
determine each half-life.
The 1 ppm RAN with no HA was exposed for three hours where time
samples were taken every half hour. The 1 ppm RAN with 1 ppm HA
was exposed for one hour with taken samples taken every ten
minutes. Both the 1 ppm RAN with 10 ppm HA and 1 ppm RAN with 20
ppm HA were taken every five minutes for a total exposure of thirty
minutes.
HPLC Method and Analysis
An important aspect of understanding how pharmaceutical drugs that find
their way into natural waters affect the environment is by examining the
degradation process that these compounds undergo. Existing compounds
need to be investigated to assess the threat they pose on aquatic and
human life. Ranitidine (RAN) is an H2 receptor antagonist widely used in
the treatment of gastric ulceration while preventing the secretion of
gastrointestinal acid. In this research project, we examined the solar
photodegradation of RAN, the active ingredient in Zantac, to ultimately
investigate the environmental fate of this commonly used over the counter
drug. Performed studies included various concentrated aqueous solutions
of RAN photoexposed to a Luzchem Solar Simulator. To accurately
determine and measure the rate of degradation and identification of
degradation products during photoexposure, we used high performance
liquid chromatography (HPLC) and liquid chromatography with mass
spectrometry (LC-MS)
The following conditions were used on a High-Pressure Liquid
Chromatography (HPLC) instrument to determine the rate of
degradation:
Agilent Technologies LC1200 Series HPLC with diode array detection
Column: Eclipse Plus C18, 4.6 mm x 150 mm, 3.5 µm
Mobile Phase: Isocratic using 0.1 M Ammonium Acetate and Methanol
Flow rate: 1.0 mL/min
Injection volume: 100 µL
Detection: UV absorption at 230 nm
Once the samples were photoexposed and analyzed by the HPLC, integrated
peak areas were recorded. The area of the RAN peaks were used to
determine the rates of degradation while the appearance of new peaks
indicates the formation of potential photodegradation products. Two
chromatograms of a 1 ppm RAN without HA solution are displayed below.
Ranitidine
Exact Mass: 314.75
Acknowledgements
Reference
Rates of Photodegradation
Latch, DE. Photochemical Fate of Pharmaceuticals in the Environment: Cimetidine and
Ranitidine Environmental Science and Technology. v. 37. no. 15. (2003): 3342-3350.
Once photoexposed, each sample was analyzed by HPLC to calculate the rate
of degradation of RAN. Using first order rate law and the corresponding half-life
equation, we effectively determined the half-life of the samples containing no
HA along with the three different concentrations.
Samples exposed to solar simulator half-life
1 ppm RAN with no Humic Acid: 95 minutes
1 ppm RAN with 1 ppm Humic Acid: 73 minutes
1 ppm RAN with 10 ppm Humic Acid: 16 minutes
1 ppm RAN with 20 ppm Humic Acid: 7 minutes
Qualitative Analysis
Using a similar mobile phase as the HPLC, only with aqueous phase slightly increased, a
standard solution of 1 ppm RAN without HA and no UV exposure was analyzed by
UHPLC-ESI-MS. Below is the chromatogram of the analyzed sample with its
corresponding m/z value, with potential degradants and impurities due to possible
hydrolysis reactions.
Ranitidine degrades quickly in aqueous solution when exposed to sunlight with a half life
of 95 minutes. The rate of degradation is increased by the use of HA, serving as the
dissolved organic matter naturally found in the environment. The HA acted as a
photosensitizer for the solar photodegradation for RAN, where increasing concentrations
of HA caused increased degradation rates.
Figure A
Figure B
Figure A. 1 ppm RAN without HA and no UV exposure.
Figure B. Same sample exposed in solar simulator for 180 minutes.
RAN
Potential Degradant
RT: 2.3 min
RAN
331.18 m/z
365.13 m/z
176.08 m/z
349.15