Research progress of enhancing quantitative sensitivity by using LC-MS(n) with derivatization method in bio-matrices / 药学学报

Liquid chromatography/mass spectrometry (LC-MS(n)) has been essential to a large number of quantitative analytical applications in drug research, and especially in the drug PK/PD research, due to its high sensitivity and high specificity. But following the appearance of drugs with high activity and low dosage and the especial structural compounds, a number of limitations of LC-MS(n) have been noted. Derivatization changes the structure of drugs and therefore changes their physical and chemical properties, resulting in high ionization efficiency, low matrix effect and low disturbance by inorganic salts and endogenous compounds in LC-MS(n). In this article, recent progress in the research of the chemical derivatization strategy with LC-MS(n) is reviewed on breakthrough of some LC-MS(n) limitations, in particular focusing on the applications involving some drugs in bio-matrices.

Determination of decapeptide LXT-101 in plasma by HPLC-MS/MS and its pharmacokinetics in Beagle dogs / 药学学报

This paper developed a sensitive and specific liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/MS) method for the determination of decapeptide LXT-101 in Beagle dog plasma. Plasma samples spiked with internal standard (IS) were treated with acetonitrile to precipitate the protein. Selected reaction monitoring (SRM) using the precursor --> product ion combinations of m/z 472.1-->587.9 and m/z 502.8-->633.8 were used to quantify LXT-101 and IS, respectively. The linear calibration curves were obtained in the concentration range of 0.5 - 500.0 ng x mL(-1). The limit of quantification (LOQ) was 0.5 ng x mL(-1). The inter-day and intra-day precision (RSD) across three validation run over the entire concentration range was below 10.9%, and the accuracy (RE) was within +/- 1.8%. The main pharmacokinetic parameters of LXT-101 after muscle injection of 20 microg x kg(-1) were as follows, AUC(0-t): (176.8 +/- 116.7) microg x h x L(-1), MRT(0-t): (2.52 +/- 0.53) h, T(1/2): (1.4 +/- 0.3) h; CL: (0.16 +/- 0.09) L x h(-1) x kg(-1), and Vd: (0.30 +/- 0.16) L x kg(-1), respectively. The method is proved to be specific, sensitive and suitable for the investigation of LXT-101 pharmacokinetics in Beagle dog.

Effect of Danxiongfang and its components on experimental liver injury models induced by CCl4 in mice / 中国中药杂志

<p><b>OBJECTIVE</b>The study investigates the protective effect on liver of Danxionfang and its components.</p><p><b>METHOD</b>Mice are injected with CCl4 to establish liver injured model. ALT, AST, serum albumin, globulin in serum and SOD, MDA in liver and liver histological changes were measured to confirm the ability of protecting liver of Danxiongfang.</p><p><b>RESULT</b>The results show Danxiongfang can inhibit obviously the abnormal increase of ALT, AST in serum and MDA in liver, enhance SOD activity in liver, total protein, albumin, globulin in serum, and decrease liver pathological changes, which suggests Danxiongfang can protect injured liver induced by CCl4.</p><p><b>CONCLUSION</b>Danxiongfang showed powerful protective effect against liver damage induced by CCl4.</p>

Anticonvulsant effect of phencynonate hydrochloride on maximal electroshock seizure and the metrazol seizure threshold test in mice / 药学学报

<p><b>AIM</b>To test the antiepileptic effect of phencynonate hydrochloride and investigate its antiepileptic mechanism.</p><p><b>METHODS</b>Through establishment of different epilepsy models, antiepileptic effects of phencynonate hydrochloride and other drugs were examined. Besides, the effect of phencynonate hydrochloride and other compounds against NMDA-induced lethality in mice, NMDA-induced injury in rat primary hippocampal neuronal cultures and NMDA-induced current were also observed.</p><p><b>RESULTS</b>Phencynonate hydrochloride produced a significant anticonvulsant effect on different epilepsy models. Furthermore, phencynonate hydrochloride also exerted its obvious protection against the lethal effects of NMDA in mice, antagonized the NMDA-induced injury in rat primary hippocampal neuronal cultures and blocked NMDA-induced current in a dose-dependent manner.</p><p><b>CONCLUSION</b>Phencynonate hydrochloride had a notable anticonvulsant effect on typical epilepsy models, its antiepileptic mechanism might relate to its antagonism against NMDA receptor.</p>

Screening of traditional Chinese remedies for SARS treatment / 中国中药杂志

The SARS epidemic is breaking out worldwide. To select suitable herbal drugs for clinical uses is important and urgent amongst the controversial treatment proposals. Nine pharmacological experimental models were used to evaluate the comprehensive efficacy of traditional Chinese remedies by cross validation in different institutes. Eight drugs were optimized for controlling different symptoms of SARS.

Identification of the metabolites of penehyclidine hydrochloride raceme in rats by LC-MS/MS and ion cluster / 药学学报

<p><b>AIM</b>To study the metabolites of penehyclidine hydrochloride (PH) raceme, a new anticholinerigic drug invented by the Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences.</p><p><b>METHODS</b>Three healthy rat urine samples were collected within 24 h after a single i.m. dose of PH raceme and PH-d5 [(5 + 5) mg.kg-1] simultaneously. The eight metabolites of PH raceme were identified by the methods of LC-MS/MS, GC-MS, FAB-MS and the stable isotope ion cluster. Mass spectrometry was operated in the positive mode for the method of LC-MS/MS.</p><p><b>RESULTS</b>M1 and M1* were identified as the oxygenated products of PH in the cyclopentyl group; M2 and M2* were as the hydroxylated products of PH in the cyclopentyl group; M3 and M3* were as the oxygented and hydroxylated products of PH at the meta-position of cyclopentyl group; M4 and M4* were identified as the dihydroxylated metabolites of PH, the hydroxylated position were at the cyclopentyl group and quiniuclidinol ring of PH. Among them, M1 and M1*, M2 and M2*, M3 and M3*, M4 and M4* were the isomers of each other.</p><p><b>CONCLUSION</b>These characteristics can be used for future structure elucidation in studies of the metabolites of PH optical isomers. The structure data of PH metabolites provide important information for the clinical use and for developing better anticholinerigic drug.</p>

RP-HPLC determination of loganin in mouse plasma and its pharmacokinetics / 药学学报

<p><b>AIM</b>To develop a method for determination of loganin in mouse plasma by using high-performance liquid chromatography. The method was employed to study pharmacokinetics of loganin.</p><p><b>METHODS</b>An RP-C18 was used as the stationary phase. The mobile phase consisted of methanol-water (30:70), at the flow-rate of 0.8 mL.min-1. The UV absorbance detector was set at 240 nm. Plasma samples were treated with solid phase extraction.</p><p><b>RESULTS</b>The recovery of loganin in mouse plasma was 86.0%-91.5%. The calibration curve in plasma was linear over the range of 0.01-5.00 micrograms.mL-1. The limit of quantitation was 10 ng.mL-1. The RSDs of intra-day and inter-day (n = 5) were less than 15%. The pharmacokinetic parameters were Cmax = 6.8 micrograms.mL-1, Tmax = 30 min, T1/2 alpha = 26.1 min, T1/2 beta = 29.01 min.</p><p><b>CONCLUSION</b>The method is accurate, sensitive and suitable for pharmcokinetic study of loganin. The absorption and elimination of loganin were rapid after ig in mice.</p>