Determination of pinostrobin in rat plasma by LC-MS/MS: application to pharmacokinetics.

A rapid and sensitive method for the determination of pinostrobin in rat plasma was developed using liquid chromatography tandem mass spectrometry (LC-MS/MS) for the first time. Isoliquiritigenin was used as an internal standard in rat plasma. Chromatographic separation was performed on an HiQ Sil C(18) column with isocratic elution at a flow rate of 1mL/min. The mobile phase consisted of water and methanol (9:91, v/v) containing 0.1% formic acid. The quantification limit was 10ng/mL within a linear range of 10-1000ng/mL (R=0.9984). The intra- and inter-day assay precision ranged from 3.8-5.3% to 3.2-5.2%, respectively, and the intra- and inter-day assay accuracy was between 93.2-95.1% and 95.5-104.3%, respectively. Our results indicated that the LC-MS/MS method is effective for pharmacokinetic study of pinostrobin in rat plasma.

Quantitative analysis of tiropramide in human plasma by gas chromatography coupled to mass spectrometry for application to a bioequivalence test.

BACKGROUND: Tiropramide is used as an antispasmodic agent. A sensitive, selective and simple gas chromatography coupled to mass spectrometry (GC/MS) was developed for quantification of tiropramide in human plasma using internal standard (ISD, (+/-) alpha-benzoylamino-4-[2-(dimethylamino) ethoxy]-N,N-dipropylbenzenepropanamide). METHODS: Tiropramide and ISD were extracted from plasma by solid-liquid extraction and analyzed on a HP-5MS column with mass selective detector. RESULTS: The retention times of tiropramide and ISD were approximately 9.8 and 10.2 min, respectively. The calibration curve showed good linearity in the concentration range 5-500 ng/ml (r2=0.998) for tiropramide in human plasma and showed good precision with CVs between 0.24% and 7.69%, respectively. The method was showed good accuracy with all intra-day (n=5) and inter-day (n=5) mean concentrations within 87.9-114.1% from nominal. The recovery of tiropramide and ISD were about 75.1% and 71.0% on the average, respectively. This method was successfully applied for the bioequivalence test of 2 formulations of tiropramide in 18 healthy male volunteers who received a single 100 mg dose of each formulation.

The skier's nose: a model of cold-induced rhinorrhea.

Cold-induced rhinorrhea (CIR) is a commonly experienced discomfort not previously addressed in the medical literature. In a 2-part study, we assessed the prevalence and described the characteristics of CIR and evaluated the efficacy of an anticholinergic nasal spray in its treatment. In Part 1, 90 general medical patients at a ski resort clinic were asked to describe their symptoms associated with cold exposure. Ninety-six percent reported some degree of CIR; 48% reported moderate to severe CIR. Fifty percent had some degree of nasal congestion and 33% reported sneezing. Allergic and nonallergic patients described similar degrees of rhinorrhea. In Part 2, 14 ski patrollers were given atropine sulfate in saline (AS/S) nasal spray before cold exposure in double-blinded placebo (P) controlled crossover fashion. Ninety-two percent noted improvement of CIR with AS/S and 8% experienced no change. None of the subjects noted worsening of symptoms, however, one subject reported excessive dryness at the AS/S concentration used. All 14 subjects receiving P experienced no change in CIR. We conclude that CIR is a distinct clinical syndrome frequently seen with cold temperature exposure, presenting primarily as rhinorrhea and sometimes involving nasal congestion and sneezing. Pretreatment with a 0.005% solution AS/S can effectively block CIR with only minimal short-term side effects.