• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.101-107
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• 2010

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of N-(-4-Chlorophenyl)-6-hydroxy-7-methoxy-2-chromanecarboxamide (KAL-1120), a novel anti-inflammation agent, in the rat plasma. The method was applied to analyze the compound in the biological fluids such as bile, urine and tissue homogenates. After liquid-liquid extraction, the compound was analyzed on an HPLC system with ultraviolet detection at 275 nm. HPLC was carried out using reversed-phase isocratic elution with a $C_{18}$ column, a mobile phase of a mixture of acetonitril (40 v/v%) at a flow rate of 1.0 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma was linear over the concentration range of 0.05-50 ${\mu}g$/mL. The intra- and inter-day assay accuracies of this method ranged from 0.06% to 9.33% of normal values and the precision did not exceed 6.28% of relative standard deviation. The plasma concentration of KAL-1120 decreased to below the quantifiable limit at 1.5 hr after the i.v. bolus administration of 2-10 mg/kg to rats ($t_{1/2,({\alpha})}$ and $t_{1/2,({\beta})$ of 2.15 and 26.7 min at a dose of 2 mg/kg, 3.91 and 33.0 min at a dose of 10 mg/kg, respectively). The steady-state volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) were not significantly altered in rats given doses from 2 to 10 mg/kg. Of the various tissues tested, KAL-1120 was mainly distributed in the lung and heart after i.v. bolus administration. KAL-1120 was detected in the bile by 30 min after its i.v. bolus administration. However, the concentration in the urine after i.v. bolus administration became too low to measure, suggesting that KAL-1120 is mostly excreted in the bile. In conclusion, this analytical method was suitable for the preclinical pharmacokinetic studies of KAL-1120 in rats.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.282-292
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• 1994

Brain perfusion SPECT shows typical regional perfusion abnormalities in Alzheimer's disease(AD) and is useful for its diagnosis. However, there is also arguement that these patterns show significant overlap with other causes, and the accuracy for SPECT in differentiating AD has shown conflicting results. We postulate that the variation in re-ported results are partly due to a difference in patient or control selection with special reference to the mixture of ischemic cerebral disease in the studied population. To deter-mine the effect of ischemic lesions and the nature of control subjects on SPECT studies for AD, we performed $^{99m}Tc$-HMPAO single photon emission computed tomography (SPECT) in 11 probable AD patients with a low (<4) Hachinski ischemic score and 12 non-demented age matched controls. Magnetic resonance imaging(MRI) disclosed ischemic cerebral lesions in 27% (3/11) of the PAD group and 25% (3/12) of the control group. Regional perfusion indices were quantitated from the SPECT images as follows and the distribution of perfusion indices from both groups were compared. This was repeated with controls after excluding those with significant ischemic lesions by MRI : regional perfusion index = average regional count/average cerebellar count All PAD patients showed perfusion abnormality in SPECT. However, 53% (10/12) of controls also showed perfusion at-normalities, and no pattern could reliably differentiate the two groups. After excluding controls with significant cerebral ischemia, the difference in temporal and parietal perfusion index was increased. A decreased tempore-parietal and any parietal or temporal per-fusion index had a sensitivity of 18% and 36% in detecting AD, respectively. When using a separate group of normal age mathced controls, the indices showed an even more difference in the temporal and parietal lobes and the sensitivity of a decreased tempore-parietal and any parietal or temporal perfusion index had a sensitivity of 36% and 55% in detecting AD, respectively. Thus, the type of control with special reference to the pres-once of ischemic cerebral lesions contribute significantly to the accuracy of perfusion SPECT in diagnosing AD. This nay have particular importance in the diagnosis of AD in populations where the prevalance of cerebrovascular disease is high.