Direct standard-free quantitation of Tamiflu and other pharmaceutical tablets using clustering agents with electrospray ionization mass spectrometry.
Accurate and rapid quantitation is advantageous to identify counterfeit and substandard pharmaceutical drugs. A standard-free electrospray ionization mass spectrometry method is used to directly determine the dosage in the prescription and over-the-counter drugs Tamiflu, Sudafed, and Dramamine. A tablet of each drug was dissolved in aqueous solution, filtered, and introduced into solutions containing a known concentration of l-tryptophan, l-phenylalanine, or prednisone as a clustering agent. The active ingredient(s) incorporates statistically into large clusters of the clustering agent where effects of differential ionization/detection are substantially reduced. From the abundances of large clusters, the dosages of the active ingredients in each of the tablets were determined to typically better than 20% accuracy even when the ionization/detection efficiency of the individual components differed by over 100x. Although this unorthodox method for quantitation is not as accurate as using conventional standards, it has the advantages that it is fast, it can be applied to mixtures where the identities of the analytes are unknown, and it can be used when suitable standards may not be readily available, such as schedule I or II controlled substances or new designer drugs that have not previously been identified.
Flick
Tawnya G
TG
Leib
Ryan D
RD
Williams
Evan R
ER
D000596:Amino Acids / Q000737:chemistry*; D004111:Dimenhydrinate / Q000032:analysis* / Q000737:chemistry; D053139:Oseltamivir / Q000032:analysis* / Q000737:chemistry; D054199:Pseudoephedrine / Q000032:analysis* / Q000737:chemistry; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets
D000596:Amino Acids; D012996:Solutions; D013607:Tablets; D053139:Oseltamivir; D054199:Pseudoephedrine; D004111:Dimenhydrinate