Quantification of the heterocyclic aromatic amine DNA adduct N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline in livers of rats using capillary liquid chromatography/microelectrospray mass spectrometry: a dose-response study.

Capillary liquid chromatography/microelectrospray-mass spectrometry (capillary LC/muESI-MS) was used to quantify DNA adducts of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of male Fischer-344 rats. Animals received a single oral dose of either 0.05, 0.50, 1.0, or 10 mg/kg IQ and were sacrificed 24 h following treatment. The major lesion identified at all doses was N-(deoxyguanosine-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ). The capillary LC/muESI-MS method provided the means for quantifying 17.5 fmol of dG-C8-IQ (2.0 adducts in 10(8) nucleosides) (S/N 10) in 300 microg of liver DNA with an intra- and interday precision of 3.5 and 6.6% (RSD), respectively. dG-C8-IQ was quantified with a mean intra- and interday accuracy of 105 +/- 26 and 106 +/- 28 (SD) based on back-calculated adduct masses from five standard curves analyzed over a four-week period. This is the first report on development of a capillary LC/muESI-MS method to quantify dG-C8-IQ adducts in liver DNA of rats following dosing with IQ at different levels. Furthermore, the ability to accurately and precisely quantify dG-C8-IQ at a level of 2.0 adducts in 10(8) nucleosides in vivo makes this method well suited for use in future studies relating carcinogen exposure to risk in humans.

Malignant ectomesenchymoma. Case report and review of the literature.

Malignant ectomesenchymoma is an uncommon neoplasm composed of neuroectodermal elements and one or more mesenchymal neoplastic elements. It is believed to arise from remnants of migratory neural crest cells (ectomesenchyme). The authors report the clinical and pathological findings of a 3-year-old girl with malignant ectomesenchymoma of the CNS. Embryogenesis of this tumor is discussed, and a review of the literature with 39 other cases is done.

Assay for the quinocarmycin analog DX-52-1 in human plasma using high-performance liquid chromatography with automated column switching and low wavelength ultraviolet detection.

The hydrocyanated derivative of the antitumor antibiotic quinocarmycin, DX-52-1 (I), exhibits impressive activity against human melanoma xenograft models in vivo. Phase I clinical trials to evaluate this compound as an antineoplastic agent have been initiated by the US National Cancer Institute. We have developed an HPLC assay for the determination of I in human plasma involving automated column switching and UV detection at 210 nm. The preparation of samples for chromatographic analysis entails the preliminary removal of plasma proteins by precipitation with acetonitrile, acidifying the clear supernatant to pH 4.5, then extracting twice with tert.-butyl methyl ether to recover the drug. A heart-cutting procedure employing two HPLC columns with contrasting retention characteristics under isocratic reversed-phase conditions was used to achieve the selectivity required for low wavelength UV detection of the analyte. The sample extract was initially loaded onto a column packed with a cyanopropyl stationary phase. During the predetermined time interval that I eluted from this column, a fully automated six-position switching valve was used to direct the effluent onto an octadecylsilane analytical column. The assay has been thoroughly validated with regard to linearity, inter- and intra-day accuracy and precision, recovery, selectivity and specificity. Using a sample volume of 1.0 ml, the lowest concentration of I quantified with acceptable day-to-day reproducibility was found to be 2.56 ng/ml (R.S.D. 18.9%, n=21, 4 months). This proved to be sufficiently sensitive for pharmacokinetic drug level monitoring in cancer patients treated with a 6-h continuous intravenous infusion of I, even at the starting dose of 3 mg/m2. The successful performance and reliability of the assay has been demonstrated through extensive application to the routine analysis of plasma specimens acquired during a phase I clinical trial of the drug.

Conductivity detection in capillary electrophoresis--a powerful tool in ion analysis.

Conductivity detection in CE has recently become available in a commercial CE instrument. The new conductivity cell is based on an end-capillary concept. The conductivity sensor and the detection end of the fused-silica capillary are permanently encapsulated in two individually modified coupling connectors (ConTip, ConCap [both from Orion Research, Boston, MA, U.S.A.]). This open-architecture cell permits interchangeability of sensors and capillaries, while maintaining a precisely defined detection volume between those two components when inserted into the detector cell block. The detector's performance is evaluated for sensitivity, linearity, and reproducibility using low-mobility electrolytes. Electropherograms comprising a variety of ionic class separations including inorganic and organic anions, organic surfactants, alkali metals, alkaline earths, transition metals, and organic amines are shown along with separations of actual samples.