Drug Content Uniformity: Quantifying Loratadine in Tablets Using a Created Raman Excipient Spectrum.

Raman spectroscopy has proven valuable for determining the composition of manufactured drug products, as well as identifying counterfeit drugs. Here we present a simple method to determine the active pharmaceutical ingredient (API) mass percent in a sample that does not require knowledge of the identities or relative mass percents of the inactive pharmaceutical ingredients (excipients). And further, we demonstrated the ability of the method to pass or fail a manufactured drug product batch based on a calculated acceptance value in accordance with the US Pharmacopeia method for content uniformity. The method was developed by fitting the Raman spectra of 30 Claritin® tablets with weighted percentages of the Raman spectrum of its API, loratadine, and a composite spectrum of the known excipients. The mean loratadine mass of 9.79 ± 40 mg per 100 mg tablet compared favorably to the 10.21 ± 0.63 mg per 100 mg tablet determined using high-performance liquid chromatography, both of which met the acceptance value to pass the 10 mg API product as labelled. The method was then applied to a generic version of the Claritin product that employed different excipients of unknown mass percents. A Raman spectrum representative of all excipients was created by subtracting the API Raman spectrum from the product spectrum. The Raman spectra of the 30 generic tablets were then fit with weighted percents of the pure loratadine spectrum and the created excipient spectrum, and used to determine a mean API mass for the tablets of 10.12 ± 40 mg, again meeting the acceptance value for the 10 mg API product. The data suggest that this simple method could be used to pass or fail manufactured drug product batches in accordance with the US Pharmacopeia method for content uniformity, without knowledge of the excipients.

Quantitative Measurements of Codeine and Fentanyl on a Surface-Enhanced Raman-Active Pad Test.

The USA is in the midst of an opioid crisis that included over 60,000 overdose fatalities in 2017, mostly unintentional. This is due to excessive use of prescription opioids and the use of very strong synthetic opioids, such as fentanyl, mixed with illicit street drugs. The ability to rapidly determine if people or packages entering the country have or contain drugs could reduce their availability, and thereby decrease the use of illicit drugs. In an effort to address this problem, we have been investigating the ability of surface-enhanced Raman spectroscopy to detect trace amounts of opioids on clothing and packages. Here, we report the measurement of codeine and fentanyl at 100 ng/mL for 5 min on a pad impregnated with gold colloids, as well as a preliminary measurement of 500 pg of fentanyl on a glass surface using one of these pads. The calculated limit of detection for this measurement was 40 pg. This data strongly suggests that these pads, used with portable Raman analyzers, would be invaluable to airport security, drug raids, crime scenes, and forensic analysis.