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Second derivative spectrophotometric determination of partition coefficients of chlorpromazine and promazine between lecithin bilayer vesicles and water

✍ Scribed by Keisuke Kitamura; Noriyuki Imayoshi; Takashi Goto; Hiroto Shiro; Takako Mano; Yuko Nakai


Publisher
Elsevier Science
Year
1995
Tongue
English
Weight
512 KB
Volume
304
Category
Article
ISSN
0003-2670

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✦ Synopsis


Absorption spectra of chlorpromazine and promazine in the presence of lecithin (egg yolk) bilayer vesicles were measured against the reference solutions containing the same amount of lecithin vesicles alone and their second derivative spectra were obtained by the Savitzky-Golay method. The residual background signal effects by the lecithin vesicles observed in the absorption spectra were entirely eliminated and both drugs clearly showed three derivative isosbestic points.

The derivative intensity change (AD) induced by the addition of the lecithin vesicles was measured at the A,,, of each drug, and from the relationship between the AD value and the lipid concentration, the partition coefficients (K,s) were calculated. The fractions of partitioned chlorpromazine and promazine calculated by using the obtained K, values agreed well with the experimental values. For the drugs which have the nature of metachromasy between the lipid vesicles and water, and even whose absorption bands overlap with the background signals by the lipid vesicles, the proposed method can be applied to the determination of their partition coefficients without disturbing the equilibrium conditions by separation procedures.


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Phosphatidylcholine (PC)-cholesterol (0 -30 mol%) unilamellar vesicles of several sizes (20 -600 nm) were prepared in buffer (pH 7.4) solutions by sonication or extrusion methods. The vesicle size was measured by a dynamic light-scattering method. Absorption spectra of chlorpromazine (CPZ) and trifl