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TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-β-diacetoxy-2-α-benzoyloxy-5-β-20-epoxy-1,13-α-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a novel semisynthetic taxane derivative. Our previous study suggested that TM-2 is a promising antitumor analogue. In this paper, the metabolism of TM-2 was investigated in rats following intravenous administration. Two different types of mass spectrometry-hybrid linear trap quadrupole orbitrap (LTQ-Orbitrap) mass spectrometry and triple-quadrupole tandem (QQQ) mass spectrometry-were employed to acquire structural information of TM-2 metabolites. A total of 17 components were identified as the metabolites of TM-2 in bile, feces, and urine samples. Accurate mass measurement using LC-LTQ-Orbitrap-MS was used to determine the accurate mass data and elemental composition of metabolites thereby confirming the proposed structures of the metabolites. The metabolites proposed were mainly oxidates of TM-2, including methoxy, hydroxyl, dihydroxy, and trihydroxyl analogues. The major metabolic pathway of TM-2 was the hydroxylation of the taxane ring or the lateral chain. These important metabolic data serve as a useful resource to support further research of TM-2.

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Schisandra chinensis (Turcz.) Baill., a traditional Chinese medicine, has been clinically used for the treatment of insomnia for centuries. The insomnia mechanism and the possible active ingredients of S. chinensis remain largely unknown. The objective of this study was to develop a method to detect its components which could pass through the blood brain barrier (BBB) by determining the brain microdialysate and brain tissue homogenate samples and then obtain the pharmacokinetic profile in brain for comprehensive understanding of its hypnotic clinical efficacy. Therefore, an efficient, sensitive and selective ultra fast liquid chromatography/tandem mass spectrometry method for the simultaneous determination of six sedative and hypnotic lignans (schisandrin, schisandrol B, schisantherin A, deoxyshisandrin, γ-schisandrin and gomisin N) of Schisandra chinensis (Turcz.) Baill. in rat brain tissue homogenate and brain microdialysates has been developed and validated. The analysis was performed on a Shim-pack XR-ODS column (75 mm × 3.0 mm, 2.2 µm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid water. The method was validated in brain homogenate and microdialysate samples, which all showed good linearity over a wide concentration range (r(2)> 0.99), and the obtained lower limit of quantification was 0.1 ng · ml(-1) for the analytes in brain microdialysate samples. The intra- and inter-day assay variability was less than 15% for all analytes. The study proved the six lignans, as sedative and hypnotic ingredients, could pass through the BBB with brain targeting, distributed mainly in the hypothalamus and possessed complete pharmacokinetics process in brain. The results also indicated that significant difference in pharmacokinetic parameters of the analytes was observed between two groups, while absorptions of these analytes in insomniac group were significantly better than those in normal group.

Opioid and ephedra alkaloids known as the active ingredients for Keke capsule, which is used to treat coughs and bronchial asthma, could have potential adverse effects on the central nervous system. Therefore, an efficient, sensitive rapid-resolution LC-MS/MS method for the simultaneous determination of morphine, ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been developed. The method was validated in the plasma and brain tissue samples, showed good linearity over a wide concentration range (r(2) > 0.99). The intra- and interday assay variability was less than 15% for all analytes, and the accuracy was between -8.8 and 5.7%. The study provided the pharmacokinetics profiles and the brain regional distribution of the three active alkaloids after oral administration of Keke capsule. The results also indicated that significant difference in pharmacokinetics parameters of the epimers was observed between ephedrine and pseudoephedrine.

A convenient and efficient method for the synthesis of 2-mercaptobenzothiazoles from disulfide and CS2 was performed by dynamic interchange reaction between a disulfide and a metal sulfide in water.

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A high-performance liquid chromatographic-mass spectrometric method was developed for the simultaneous determination of 10 flavonoids in Viscum coloratum obtained from different host species and different sources. Viscum coloratum was extracted with 50% methanol. The extracts were separated on a C(18) column with a gradient of 0.1% (v/v) formic acid and methanol. The flavonoids in the extracts were detected by negative electrospray ionization mass spectrometry in selective ion monitoring mode. The calibration curves showed good linearity (r>0.998) within the test ranges (homoeriodictyol: 0.149-8.940 µg/ml, homoeriodictyol-7-O-β-D-glycoside: 0.230-13.80 µg/ml, homoeriodictyol-7-O-β-D-apiose (1→2)-β-D-glycoside: 5.000-300.0 µg/ml, homoeriodictyol-7-O-β-D-apiose (1→5)-β-D-apiose (1→2)-β-D-glycoside: 0.835-125.3 µg/ml, rhamnazin-3-O-β-D-glucoside: 0.064-3.840 µg/ml, rhamnazin-3-O-β-D-(6″-β-hydroxy-β-methyglutaryl)-glucoside: 1.435-86.10 µg/ml, isorhamnetin-3-O-β-D-glucoside: 0.930-55.80 µg/ml, 5-hydroxy-3,7,3'-trimethoxyflavone-4'-O-β-D-glucoside: 0.067-4.020 µg/ml, 5,7,4'-trihydroxy-3,3'-dimethoxyflavone: 0.270-16.20 µg/ml, pachypodol: 0.110-6.600 µg/ml). The limits of quantification were between 0.006-0.720 µg/ml. The assay was reproducible and the overall intra- and inter-day variations were less than 4.6%. The recoveries varied from 93.4 to 103.9% at three different concentration levels. The validation method was used to determine the contents of 10 flavonoids in Viscum coloratum. A one-way analysis of variance was applied to evaluate Viscum coloratum-host-source interactions. Compared with the host species, the sample source had a significant impact on the sample content.