No abstract

No abstract

No abstract

High-performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) using an electrospray ionization (ESI) interface provides a sensitive method for the quantitative analysis of peptide drugs in complex biological matrixes. ESI HPLC-MS was applied to the analysis of a pentapeptide drug (IRI-514) in rabbit and human plasma. Prior to analysis, the plasma samples were prepared using protein precipitation followed by solid-phase extraction. The lower limit of quantitation using selected ion monitoring was determined to be 2 ng/mL, when 8 mL of human plasma spiked with 1-40 ng/mL was extracted. Rabbit plasma (1 mL) samples spiked with 10-40,000 ng of authentic drug/mL gave a linear response when a deuterated peptide analog was employed as an internal standard. A commercial ESI interface was modified to permit higher flow rates (10-20 microL/min) to enter the mass spectrometer source. The revised interface provided a 10-fold increase in sensitivities and permitted the use of standard HPLC columns (2.0-mm i.d.) and HPLC instrumentation. ESI HPLC-MS analysis was automated to provide unattended, precise, and sensitive detection of small peptides in both human and rabbit plasma. Using this methodology, a toxicokinetic study of intravenously administered IRI-514 at three dose levels indicated that the area under the curve values were dose proportional.

119Sn nuclear magnetic relaxation times were measured for the two symmetric top chloroiodides of tin in the liquid state using pulsed nuclear magnetic resonance. The temperature and magnetic field dependence of TI and T2 of 119Sn in SnCl 3 1 and Snl3Cl were studied to identify and separate relaxation mechanisms. The longitudinal relaxation rates were found to arise from competing scalar and spin-rotation interactions, while the transverse rates are completely scalar dominated. Tl's of both SnlCl 3 and SnCl 3 1 show evidence of a maximum in (Tl)~~lar when Tl 127 1) equals the difference of the 119Sn and 1271 Larmor frequencies. This behavior is predicted by Abragam's "scalar relaxation of the second kind." The maximum occurs near the melting points in a 5 kG field and was used indirectly to determine 1271 relaxation times. A least·squares analysis of these results permitted direct determination of three tin-halogen scalar coupling constants: JC19Sn_1271) = 1638 Hz for SnC1 3 1. JCI9Sn_1271) = 1097 Hz for Sn1 3 Cl. and J( II9 Sn_ 35 Cl) = 421 Hz for Snl3CI.Rotational correlation times and halogen relaxation times were also measured as a function of temperature. The analysis failed to reveal a TI component due to chemical shift anisotropy for any of the compounds at or below 13.3 kG. A comparison of molecular rotational correlation times with those of the unmixed tetrahalides. SnCI. and Snl •• indicates that electric dipole forces and shape effects associated with deviations from tetrahedral symmetry are less important determinants of the rotational diffusion tensor than is intermolecular rotational friction resulting from London dispersion forces. The effect on rotational diffusion constants of varying the composition of the medium was examined and found to be small.