Determination of active ingredient within pharmaceutical preparations using flow injection mass spectrometry.

Two separate pharmaceutical blends, one containing 2% caffeine by weight, the other containing 2% creatine by weight, and 200 mg caffeine tablets were examined in this study. The purpose of the analyses was to determine the feasibility of using flow injection mass spectrometry for the quantitative analysis of active ingredient within a drug product or other form of pharmaceutical preparation. For more precise and accurate measurements, it was necessary to incorporate an internal reference within the samples. Further, flow injection analysis showed to provide quicker, more facile method development than the application of chromatographic separation. Samples were analyzed over an analyte concentration range of 5.0-15.0 microg/mL. Analyte selectivity was obtained through the observance of the (M+H)(+) ions generated by positive electrospray ionization of each of the analytes (m/z 195 for caffeine and m/z 132 for creatine), and accurate quantitation was achieved by determining the ratio of the analyte response versus the response of the incorporated reference compound. Sample-to-sample precision in these measurements was less than 3%, recovery values were shown to be accurate to within +/-3% of the actual values, and both analytical methods proved to be linear over the assay range (R(2)> or =0.999). Due to the excellent selectivity and low detection limits available to mass spectrometric detection, flow injection mass spectrometric analysis could be particularly applicable for analysis of formulations that contain either low doses of active ingredient, active ingredient with low solubility, or active ingredient that does not possess a strong chromophore. Additionally, this type of methodology shows to be conducive for rapid method development.

Silylation of an OH-terminated self-assembled monolayer surface through low-energy collisions of ions: a novel route to synthesis and patterning of surfaces.

Using a multi-sector ion-surface scattering mass spectrometer, reagent ions of the general form SiR(3) (+) were mass and energy selected and then made to collide with a hydroxy-terminated self-assembled monolayer (HO-SAM) surface at energies of approximately 15 eV. These ion-surface interactions result in covalent transformation of the terminal hydroxy groups at the surface into the corresponding silyl ethers due to Si--O bond formation. The modified surface was characterized in situ by chemical sputtering, a low-energy ion-surface scattering experiment. These data indicate that the ion-surface reactions have high yields (i.e. surface reactants converted to products). Surface reactions with Si(OCH(3))(3) (+), followed by chemical sputtering using CF(3) (+), yielded the reagent ion, Si(OCH(3))(3) (+), and several of its fragments. Other sputtered ions, namely SiH(OCH(3))(2)OH(2) (+) and SiH(2)(OCH(3))OH(2) (+), contain the newly formed Si--O bond and provide direct evidence for the covalent modification reaction. Chemical sputtering of modified surfaces, performed using CF(3) (+), was evaluated over a range of collision energies. The results showed that the energy transferred to the sputtered ions, as measured by their extent of fragmentation in the scattered ion mass spectra, was essentially independent of the collision energy of the projectile, thus pointing to the occurrence of reactive sputtering.A set of silyl cations, including SiBr(3) (+), Si(C(2)H(3))(3) (+) and Si(CH(3))(2)F(+), were similarly used to modify the HO-SAM surface at low collision energies. A reaction mechanism consisting of direct electrophilic attack by the cationic projectiles is supported by evidence of increased reactivity for these reagent ions with increases in the calculated positive charge at the electron-deficient silicon atom of each of these cations. In a sequential set of reactions, 12 eV deuterated trimethylsilyl cations, Si(CD(3))(3) (+), were used first as the reagent ions to modify covalently a HO-SAM surface. Subsequently, 70 eV SiCl(3) (+) ions were used to modify the surface further. In addition to yielding sputtered ions of the modified surface, SiCl(3) (+) reacted with both modified and unmodified groups on the surface, giving rise not only to such scattered product ions as SiCl(2)OH(+) and SiCl(2)H(+), but also to SiCl(2)CD(3) (+) and SiCl(2)D(+). This result demonstrates that selective, multi-step reactions can be performed at a surface through low-energy ionic collisions. Such processes are potentially useful for the construction of novel surfaces from a monolayer substrate and for chemical patterning of surfaces with functional groups.

Surface modification and patterning using low-energy ion beams: Si-O bond formation at the vacuum/adsorbate interface.

Modification of hydroxyl-terminated self-assembled monolayer (HO-SAM) surfaces by collision of low-energy (15 eV) hyperthermal Si(CH3)3+ ions is shown to lead to Si-O bond formation and terminal trimethylsilyl ether formation. Modification was verified by in situ mass spectrometry using chemical sputtering with CF3+ ions (70 eV), ex situ secondary ion mass spectrometric analysis (12 kV Ga+ primary ion beam), and through X-ray photoelectron spectroscopy by monitoring Si (2s). The nature of the surface modification was further established by analysis of synthetic SAM surfaces made up of mixtures of the trimethylsilyl-11-mercapto-1-undecane ether and various proportions of the hydroxyl-terminated mercaptan (11-mercapto-1-undecanol). These mixed surfaces, as well as the spectroscopic data, indicate that ca. 30% of the hydroxyl chains are covalently modified at saturation coverage. Analogous surface transformations are achieved using Si(CH3)2F+ and Si(CH3)2C6H5+.