Determination of unlabeled and 13C6-labeled moricizine in human plasma using thermospray liquid chromatography-mass spectrometry.

Moricizine hydrochloride is an orally effective antiarrhythmic agent currently marketed in the Soviet Union and undergoing clinical testing in the United States. To facilitate the simultaneous analysis of unlabeled and 13C6-labeled moricizine in human plasma, a specific and sensitive method employing liquid-liquid extraction followed by thermospray liquid chromatography-mass spectrometry (LC-MS) was developed. Plasma samples, after addition of [2H11]moricizine as an internal standard, were extracted into methylene chloride under alkaline conditions. Extracts were evaporated, reconstituted with mobile phase, and chromatographed on an ODS column. The LC mobile phase consisted of methanol-0.1 M ammonium acetate containing 0.2% triethylamine (65:35) and it was used at a flow-rate of 1.5 ml/min. Under these conditions, moricizine and [13C6]moricizine coeluted at 1.2 min, while [2H11]moricizine eluted slightly earlier. The MS system consisted of a Finnigan 4600 TSQ and a Vestec thermospray interface. Selected ions at m/z 428, 434, and 439 were scanned at 0.2 s per ion. Over a plasma concentration range of 10-800 ng/ml, intra-day precision (n = 3) ranged from 1.8 to 13.3% and intra-day accuracy ranged from 1.9 to 15.8%. This method was successfully used to assay human plasma samples from a pilot moricizine bioavailability study in which tablets and solution containing moricizine hydrochloride and [13C6]moricizine, respectively, were simultaneously administered.

Mass spectral investigations on trichothecene mycotoxins. VIII--Thermospray ionization and collisionally activated dissociation of macrocyclic trichothecenes.

Several structurally similar, biologically active macrocyclic trichothecenes were ionized under thermospray conditions followed by collisionally activated dissociation of the ammonium adducts. Most of the observed daughter ions were formed by bond cleavage at the exocyclic ester bridges. Compounds with similar ester bridges formed several common daughter ions and underwent similar neutral losses. Fragmentation pathways proposed for the dissociation of the adducts were confirmed from the corresponding neutral loss spectra. Simple experiments designed for the sequential monitoring of the characteristic daughter ions were used for the rapid, direct and accurate analysis of macrocyclic trichothecenes in real samples. The primary drawback of the method is its inability to distinguish between isomers.

Mass spectral investigations on trichothecene mycotoxins. VII. Liquid chromatographic-thermospray mass spectrometric analysis of macrocyclic trichothecenes.

Thermally labile, polar toxic roridins and biologically active, isomeric baccharinoids were separated on a reversed-phase high-performance liquid chromatography column and effectively ionized under thermospray ionization conditions. The mass spectra indicated the formation of corresponding molecular ion-ammonium adducts in great abundance. Experiments designed for monitoring specific ions of these analytes at predesignated intervals were utilized for the accurate analysis of these macrocyclic trichothecenes in real, crude samples. A synthetically modified macrocyclic trichothecene, 8-ketoverrucarin A, was used as the internal standard for the detection and quantification of these compounds. Minimum detectable limits, during this first reported method for the unambiguous analysis of these structurally related macrocyclic trichothecenes, were determined to be 2-5 ng.

Confirmatory assay for ivermectin in cattle tissue using chemical ionization mass spectrometry/mass spectrometry (MS/MS).

A method based on direct exposure, positive ion, chemical ionization mass spectrometry/mass spectrometry (ms/ms) was developed for the confirmatory assay of the antiparasitic drug, ivermectin, in animal tissue. Following extraction, column and preparative liquid chromatography, mass spectrometric/mass spectrometric analysis of the drug in liver samples provided reliable detection limits to 8-10 parts-per-billion at a signal: noise of greater than 10:1. Blank tissue consistently displayed no chemical/matrix interference. Besides the development of a confirmatory assay, the study also demonstrates the analytical capability and the role of MS/MS vis-a-vis other applied mass spectrometric techniques.