Wilson J. Yasaka

Validation of HPLC stability-indicating method for Vitamin C in semisolid pharmaceutical/cosmetic preparations with glutathione and sodium metabisulfite, as antioxidants.

HPLC stability-indicating method was validated for Vitamin C (ascorbic acid) in semisolid pharmaceutical/cosmetic formulations containing glutathione and sodium metabisulfite, as antioxidants. The described procedure included a reliable, precise, accurate and specific method determination employing a 250mm x 4.6mm C(18) column, 0.2% metaphosphoric acid/methanol/acetonitrile (90:8:2, v/v/v) as the mobile phase and detection at 254nm. Nicotinic and ascorbic acids were employed as standards, both presenting purity of 99.0%. Linearity was established for the ascorbic acid concentrations ranging form 1.0 to 12microg mL(-1), accuracy/recovery percentage was 95.46-101.54%, precision values were 0.38 (intra-day) and 1.22% (inter-days), and LOD and LOQ were found to be 0.05 and 0.17microg mL(-1), respectively. The working mobile phase elevated the ascorbic acid retention time to approximately 3.5min at a flow rate of 1.0mL min(-1) and provided resolution of the active from the nicotinic acid (internal standard), degradation product (oxalic acid) and other excipients from the pharmaceutical/cosmetic preparations.

Inhibitory effects of beryllium chloride on rat liver microsomal enzymes.

A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

Lymphatic transport of salicylates in dogs.

1. Pharmacokinetic parameters were determined for acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma and lymph following the intravenous or oral administration of a water-soluble preparation of lysine-acetylsalicylic acid to dogs. 2. By both routes of administration, ASA but not SA, tended to be deposited in lymph, as indicated by the ratio between the area under the concentration-time curve constructed for the parent compound and its metabolite in lymph and plasma. 3. A reduced conversion of ASA to SA by esterases in lymph, and lymphatic absorption of ASA following the oral administration might be factors responsible for the accumulation of the compound in the lymphatic system. 4. It is suggested that the lymphatic system might serve as a temporary reservoir compartment for ASA.

Some characteristics of acute inflammation induced by econazole

Aqueous suspension of econazole nitrate injected into subplantar region of rat foot induces a sharp and long-lasting inflammation. The econazole-induced edema is characterized by the existence of two phases of accelerated evolution, with peak values at 2nd and 12th hr after injection. Only the second phase of econazole-induced edema is selectively inhibited by either steroidal or non-steroidal anti-inflammatory drugs.

Effect of praseodymium chloride on liver microsomal enzymes of rats.

A single i.v. dose (5 mg/kg) of a light lanthanon, praseodymium, prolonged the duration of hexobarbital-induced sleep and zoxazolamine-induced paralysis, as well as it modified pharmacokinetic parameters of hexobarbital and zoxazolamine, in rats. Half-lives (t1/2) and area under the curve (AUC) were increased, while elimination coefficient (beta) and clearance (Cl) were decreased. However, in daily doses of 1 mg/kg i.p. for 15 days, praseodymium did not alter pharmacological effects and pharmacokinetic parameters. The in vitro hydroxylation of hexobarbital and zoxazolamine by liver microsomes was inhibited when the animals were treated previously with a single i.v. dose (5 mg/kg) of praseodymium chloride. In these animals, the amount of cytochromes P-450 and b5 were reduced significantly, whereas that of NADPH-cytochrome c reductase remained unchanged. The pretreatment of animals with phenobarbital normalized the microsomal enzyme impairment caused by praseodymium.