Enantioselective analysis of pheniramine in rat using large volume sample stacking or cation-selective exhaustive injection and sweeping coupled with cyclodextrin modified electrokinetic chromatography.

For the aim of simultaneously performing the enantioseparation and determination of the trace enantiomers in plasma samples, enantioseparation by HPLC using five kinds of chiral stationary phases were initially investigated. But unfortunately, enantioseparation could not be detected in reversed mobile phase mode with all the five columns. For this reason, two simple, economical and highly efficient online preconcentration methods, large volume sample stacking and sweeping (LVSS-sweeping) and cation-selective exhaustive injection and sweeping (CSEI-sweeping) both followed by the cyclodextrin modified electrokinetic chromatography (CDEKC) were examined in the present work. Parameters affecting the enantioseparation and enhancement efficiency of these two injection modes were monitored in detail, and migration order of the two enantiomers was identified by circular dichroism (CD) and HPLC. Upon optimization, two enantiomers were best separated with the improvement of sensitivity reaching 160-fold and 4000-fold respectively for LVSS-sweeping and CSEI-sweeping comparing with the normal CDEKC separation. Then the optimal condition of CSEI-sweeping-CDEKC was validated and showed high sensitivity (10 ng/mL for lower limit of quantification, LLOQ), satisfactory accuracy (96.8-111.6%) and precision (relative standard deviation, RSD within 9.4%). This demonstrated it to be a suitable strategy for the rapid enantioselective determination and quantitative analysis of pheniramine enantiomers in plasma samples. Therefore, the method was further applied in the enantiomeric analysis of pheniramine in rat pharmacokinetics and plasma protein binding investigations. Stereoselectivity in pharmacokinetics as well as plasma protein binding were observed, suggesting that the stereoselective protein binding might be responsible for the stereoselectivity in pharmacokinetics.

Trace analysis of three antihistamines in human urine by on-line single drop liquid-liquid-liquid microextraction coupled to sweeping micellar electrokinetic chromatography and its application to pharmacokinetic study.

A rapid and efficient dual preconcentration method of on-line single drop liquid-liquid-liquid microextraction (SD-LLLME) coupled to sweeping micellar electrokinetic chromatography (MEKC) was developed for trace analysis of three antihistamines (mizolastine, chlorpheniramine and pheniramine) in human urine. Three analytes were firstly extracted from donor phase (4 mL urine sample) adjusted to alkaline condition (0.5 M NaOH). The unionized analytes were subsequently extracted into a drop of n-octanol layered over the urine sample, and then into a microdrop of acceptor phase (100 mM H(3)PO(4)) suspended from a capillary inlet. The enriched acceptor phase was on-line injected into capillary with a height difference and then analyzed directly by sweeping MEKC. Good linear relationships were obtained for all analytes in a range of 6.25 × 10(-6) to 2.5 × 10(-4)g/L with correlation coefficients (r) higher than 0.987. The proposed method achieved limits of detections (LOD) varied from 1.2 × 10(-7) to 9.5 × 10(-7)g/L based on a signal-to-noise of 3 (S/N=3) with 751- to 1372-fold increases in detection sensitivity for analytes, and it was successfully applied to the pharmacokinetic study of three antihistamines in human urine after an oral administration. The results demonstrated that this method was a promising combination for the rapid trace analysis of antihistamines in human urine with the advantages of operation simplicity, high enrichment factor and little solvent consumption.

Five-minute removal of soft lenses prevents most absorption of a topical ophthalmic solution.

PURPOSE: Patients who use topical ophthalmic medications and wear soft contact lenses must remove their lenses before drop instillation to prevent absorption of the medication into the lenses. No previous study has examined how long such a patient should wait before reinserting their lenses. This study was designed to test the hypothesis that waiting 5 minutes before reinsertion of lenses would be sufficient to reduce absorption to a level below what is needed to produce a physiological response. METHODS: Naphcon-A was used as the test solution and pupillary dilation was the physiological response measured. The amount of benzalkonium chloride (BAC) extracted from the lenses was also measured. Twenty-three subjects, none of whom had any significant ocular or systemic abnormalities nor showed pupillary dilation to directly applied Naphcon-A, completed this 3-week study. The study used a 2-period crossover design with a 1-week screening phase. Results were analyzed with a repeated-measure analysis of variance. RESULTS: The pupils averaged 0.316 mm larger when subjects instilled Naphcon-A with lenses in place as compared to when dosing with lenses removed for 5 minutes (P = 0.0008). Nine of 23 subjects showed pupillary dilation greater than 0.5 mm when dosing with lenses in place as compared to none when lenses were removed for 5 minutes. Significantly (P < 0.01) more BAC was extracted from lenses that had been worn during dosing than from lenses removed for 5 minutes (0.9 microgram/lens as compared to no detectible amount). CONCLUSION: Removing soft contact lenses for 5 minutes was sufficient to prevent absorption of clinically significant amounts of Naphcon-A into the lenses.

Determination of loratadine and pheniramine from human serum by gas chromatography-mass spectrometry.

In this work, a method for the determination of the antihistaminic drugs loratadine and pheniramine from human serum is presented. Serum samples are extracted under basic conditions with hexane-n-amyl alcohol (95:5, v/v), the analytes are reextracted into diluted hydrochloric acid and, after basification, are once again extracted into the organic phase. The samples are measured by GC-MS. The limits o detection of the assay are 0.5 ng/ml for loratadine and 2 ng/ml for pheniramine. The R.S.D.s in the day-to-day precision test for loratadine are 7.0% at 20 ng/ml and 12.4% at 2 ng/ml. for pheniramine, the R.S.D. are 6.4% at 300 ng/ml and 10.2% at 20 ng/ml.

[Sudden infant death--fatal poisoning with pheniramine]. / Plötzlicher Säuglingstod--letale Intoxikation mit Pheniramin.

A case of unintentional fatal intoxication of a 10 month-old baby with the anti-histamine Pheniramine (Avil) is reported. On the face value and without an autopsy this case parallels familiar cases of SIDS and had for this reason been certified as such. Autopsy, however, revealed 32 partly dissolved tablets which proved to be Phenyramine. High concentrations of Pheniramine were found in body fluids and various tissues. According to official investigations, the tablets were offered to the baby by his 3 1/2 year old sister who probably believed they were sweets.