A new, simple procedure is described for the direct gas chromatographic determination of sphingolipid bases as their trimethylsilyl derivatives. This method is used to study the nature of the mixture of bases produced by acidic methanolysis of ceramides, sphingomyelins, free sphingolipid bases, andN‐acetyl derivatives of the latter. Cleavage of sphingolipids with anhydrous methanolic hydrogen chloride results in the production of considerable quantities of secondary products from sphingosine, such as theO‐methyl ethers, which are not formed during methanolysis of free sphingosine. A modified reagent for methanolysis, containing methanol, water and hydrochloric acid, reduces the yield of these by‐products to low levels. Preliminary purification of the sphingolipid bases, before gas chromatography, is achieved by chromatographic procedures. Evidence is presented for the occurrence of C16‐sphingosine in sphingomyelin from human blood plasma.
Carboplatin was administered i.v. to four groups of three male beagle dogs at doses of 3, 6, 12, and 24 mg/kg (60-580 mg/m2). Plasma samples were obtained at appropriate times and protein-free plasma ultrafiltrates (PU) were generated with Amicon Centrifree micropartition systems. Urine was collected at 24-h intervals for 96 h. PU and urine samples were analyzed for carboplatin by HPLC and for total platinum by atomic absorption spectrophotometry. Carboplatin accounted for about 90% of the free platinum in plasma. The Cmax and AUCinf values for carboplatin and for free platinum increased linearly with dose. The terminal elimination half-life and mean residence times for carboplatin and free platinum were each about 1 h. Total-body clearances for carboplatin (5.6 l/h per m2) and free platinum (5.1 l/h per m2) were constant over the dose range studied, as were the respective volumes of distribution (5.7 and 5.0 l/m2). A mean of 46% of the dose was excreted as carboplatin in 24-h urine; and by 72 h, 70% of the platinum administered was excreted in the urine. Free platinum was cleared by both renal and non-renal processes. These results show that a dose of carboplatin is rapidly excreted in the urine and that carboplatin and plasma-free platinum exhibit linear pharmacokinetics in the beagle dog.
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