Enantioseparation in capillary electrophoresis using 2-O-(2-hydroxybutyl)-beta-CD as a chiral selector

The resolving ability of 2-O-(2-hydroxybutyl)-beta-CD (HB-beta-CD) with different degrees of substitution (DS = 2.9 and 4.0) as a chiral selector in CZE is reported in this work. Fourteen chiral drugs belonging to different classes of compounds of pharmaceutical interest such as beta-agonists, antifungal agents, ageneric agents, etc., were resolved. The effects of the DS of HB-beta-CD on separations were also investigated. The chiral resolution (R(s)) was strongly influenced by the concentrations of the CD derivative, the BGE, and the pH of the BGE. Under the conditions of 50 mmol/L Tris-phosphate buffer at pH 2.5 containing 5 mmol/L HB-beta-CD, all 14 analytes were separated. The very low concentration necessary to obtain separation was particularly impressive. The DS had a significant effect on the resolution of the chiral drugs and the ionic strength of the separation media; hence, the use of a well-characterized CD derivative is crucial.     

Separation of enantiomers in capillary electrophoresis with contactless conductivity detection

Contactless conductivity detection is successfully demonstrated for the enantiomeric separation of basic drugs and amino acids in capillary electrophoresis (CE). Derivatization of the compounds or the addition of a visualization agent as for indirect optical detection schemes were not needed. Non-charged chiral selectors were employed, hydroxypropylated cyclodextrin (CD) for the more lipophilic basic drugs and 18-crown-6-tetracarboxylic acid (18C6H4) for the amino acids. Acidic buffer solutions based on lactic or citric acid were used. The detection limits were determined as 0.3 microM for pseudoephedrine as an example of a basic drug and were in the range from 2.5 to 20 microM for the amino acids.     

符合经典构效关系的抗肿瘤铂类药物

综述了自顺铂、卡铂后符合经典构效关系的铂类抗肿瘤药物的发展概况，按载体配基和离去基团的结构特征进行了分类，总结了各类配合物的构效关系和临床进展，其中重点对手性二胺配体的铂(Ⅱ)配合物进行了介绍。并讨论了顺铂、卡铂、奥沙利铂的作用机理。     

Micellar Liquid Chromatography Study of Quantitative Retention–Activity Relationships for Antihypertensive Drugs

Use of micellar mobile phases in reversed-phase liquid chromatography (RPLC) results in hydrophobic and electrostatic sites for interaction. Modified stationary phases in micellar liquid chromatography (MLC) are structurally similar to biomembranes. To confirm this we focused on the effects of the type and concentration of surfactant (Brij 35, SDS, and CTAB) and mobile phase pH on the retention of antihypertensive drugs on modified C₁₈ stationary phases. Quantitative retention-activity relationships are proposed for the drugs and the different surfactants and compared with those obtained using aqueous–organic mobile phases. Finally, a correlation was obtained between the logarithm of retention factors (log k) and the toxicity (LD₅₀) of antihypertensive drugs. Revised: 14 September 2005 and 4 April 2006     

Magnetic microcapsules for targeted delivery of anticancer drugs

To achieve targeted distribution of anticancer drugs with sustained activity, ferromagnetic ethylcellulose microcapsules containing an anticancer drug, mitomycin C (FM-MMC-mc), were prepared by a method based on phase separation principles. Two prototypes of FM-MMC-mc were made: one with the drug as the core and zinc ferrite on its capsular surface (outer type); the other with both the drug and zinc ferrite as the core (inner type). Both preparations provided a sustained-release property and a sensitive response to conventional magnetic force, although certain differences in the release rate of drug, magnetic responsiveness, and particle size were found between the two dosage forms. Animal studies showed that the magnetic microcapsules could be magnetically controlled in the artery and urinary bladder. VX2 tumors in the rabbit hind limb and urinary bladder were successfully treated with magnetic control of FM-MMC-mc. Pharmacokinetic study revealed that the targeting of the microcapsules markedly enhanced the drug absorption into the surrounding tissues for a prolonged period of time. The results indicate the feasibility and effectiveness of the magnetic microcapsules as a targeted drug delivery system.     

Cationic vesicles as chiral selector for enantioseparations of nonsteroidal antiinflammatory drugs by micellar electrokinetic chromatography

A vesicle-forming chiral cationic surfactant (1R,2S)-(-)-N-dodecyl-N-methyl-ephedrinium bromide was evaluated as a pseudo-stationary phase in micellar electrokinetic chromatography (MEKC) for enantioseparation of eight non-steroidal anti-inflammatory drugs e.g., carprofen, flurbiprofen, fenoprofen, ibuprofen, indoprofen, ketoprofen, naproxen and suprofen by capillary electrophoresis. The effects of varying experimental conditions such as pH and concentration of surfactant in the running buffer on the enantiomer separation of the drugs are reported. A mixture of five of the above drugs was separated and each enantiomeric pair was also separated simultaneously in a single run by use of the surfactant. The strong electrostatic interactions between the analytes and the vesicles seemed to have a major role in the enantiomeric separation of the profens.     

Speciation analysis of platinum antitumoral drugs in impacted tissues

Chemical compounds containing platinum have been employed since 1978 as drugs to beat certain type of tumours. Nevertheless, besides of their exceptional antitumoral properties, these drugs also have important deleterious side effects, such as, nephrotoxicity and ototoxicity.A study of Pt accumulation and a speciation analysis has been performed by ICP-MS in samples from kidney and inner ear in a controlled population of Wistar rats treated with, either, cisplatin, carboplatin or oxaliplatin. The results on Pt accumulation point out to drug structure and not only to Pt content as the responsible for the alteration of organ functionality.Speciation studies in the samples from kidney and inner ear were performed coupling two-dimensional liquid chromatography (2D-LC) to ICP-MS. Size exclusion (SEC) and anion exchange fast protein liquid chromatography (FPLC) was employed for 2D orthogonal separation. After these separations, free drug peaks were not observed in any of the samples.The binding of Pt to biomolecules was demonstrated by SEC and, independently of the drug used, Pt eluted as two main bands with molecular weights of 12 kDa and 25-65 kDa for inner ear samples, and as two different bands with 20 kDa and 50-60 kDa in the samples from kidney. However, the relative band intensity presented important differences for the three drugs. Using the same chromatographic conditions, it was shown that a metallothionein (MT) standard eluted in the same position as some of the cytosolic Pt-biomolecules.High Pt-containing fractions eluting from the SEC column were analysed by anion exchange FPLC after a preconcentration step. Among the different preconcentration methods tested, sample focusing on the head of the FPLC column shows main advantages. In this way, the separation by 2D chromatography of the high molecular Pt-species has been considerably improved.     

Sequential injection spectrophotometric determination of phenylephrine hydrochloride in pharmaceutical preparations

A fully automated sequential injection spectrophotometric method for the determination of phenylephrine hydrochloride in pharmaceutical preparations is reported. The method is based on the condensation reaction of the analyte with 4-aminoantipyrine in the presence of potassium ferricyanide. The absorbance of the condensation product was monitored at 503 nm. A linear relationship between the relative peak height and concentration was obtained in the range 0.5-17.5 mg l⁻¹. The detection limit (as 3σ value) was 0.09 mg l⁻¹ and repeatability was 0.8 and 0.6% at 2.5 and 5 mg l⁻¹, respectively. Results obtained by this method agreed very well with those obtained by the AOAC official method.