Time course of plasma drug levels during once-daily oral administration of clomipramine

Fourteen depressed in-patients were treated with 150 mg clomipramine (CLO) daily, given as one oral dose. Using a gas-chromatographic method, concentrations of CLO and desmethyl clomipramine (DMCLO) were determined in plasma samples taken at frequent intervals during 24h. The plasma level of each compound 12 h after the dose correlated well with the average value in the same patient, calculated over the whole 24-h period. Levels at other times gave poorer correlations, and at 24 h it was particularly poor. Plasma DMCLO concentrations were usually maximum 4–6 h after the dose. The ratios of maximum to minimum levels averaged only 1.31±0.15 SD. Peak CLO levels occurred 3 or 4 h after the dose. Maximum: minimum ratios averaged 2.72±0.73 SD, contrasting with the much smaller fluctuations of plasma nortriptyline (NT) levels observed in patients given this drug once daily. The difference is not due to a shorter half-life of CLO, but to the absorption and/or distribution behaviour of the two drugs. Although not fully understood, this difference between tertiary and secondary amines appears to hold generally among the tricyclic antidepressants.     

保健食品中非法添加西地那非衍生物的确证

目的：对在保健食品中发现的一种非法添加的西地那非衍生物进行确证。方法：采用高效液相色谱-二极管阵列检测器（HPLC-DAD）技术在日常检测保健食品非法添加时发现一种新型西地那非衍生物。经制备液相法分离纯化得到该化合物,采用高效液相色谱-二级质谱联用（LC-MS/MS）技术获得该化合物准分子离子和碎片离子,并进一步通过核磁共振氢谱确认,结合文献分析,最终确证该化合物。结果：该化合物分子式C₂₃H₃₀N₆O₃,分子量438,结构为去甲基卡波地那非。结论：去甲基卡波地那非在国内未被报道,是一种新型PDE-5抑制剂。     

More and more toxins around–analysis of cyanobacterial strains isolated from Lake Chao (Anhui Province, China)

Lake Chao, China, is highly eutrophicated and experiences recurrent dense cyanobacterial blooms. Its surface water is used as drinking water resource for Hefei city, hence the potential toxicity of those cyanobacteria was of interest. Sixteen isolated strains of Microcystis aeruginosa evidenced that non-toxic, toxic and highly toxic strains coexist in the lake. Microcystin variants within one strain ranged up to 11, the concentration up to 4.799 mg g DW⁻¹. Mass spectrometry analysis confirmed desmethylated microcystin variants.     

Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation

A new method for the simultaneous determination of celecoxib, erlotinib, and its active metabolite desmethyl-erlotinib (OSI-420) in rat plasma, by liquid chromatography/tandem mass spectrometry with positive/negative ion-switching electrospray ionization mode, was developed and validated. Protein precipitation with methanol was selected as the method for preparing the samples. The analytes were separated on a reverse-phase C₁₈ column (50mm×4.6mm i.d., 3μ) using methanol: 2 mM ammonium acetate buffer, and pH 4.0 as the mobile phase at a flow rate 0.8 mL/min. Sitagliptin and Efervirenz were used as the internal standards for quantification. The determination was carried out on a Theremo Finnigan Quantam ultra triple-quadrupole mass spectrometer, operated in selected reaction monitoring (SRM) mode using the following transitions monitored simultaneously: positive m/z 394.5→278.1 for erlotinib, m/z 380.3→278.1 for desmethyl erlotinib (OSI-420), and negative m/z −380.1→ −316.3 for celecoxib. The limits of quantification (LOQs) were 1.5 ng/mL for Celecoxib, erlotinib, and OSI-420. Within- and between-day accuracy and precision of the validated method were within the acceptable limits of < 15% at all concentrations. The quantitation method was successfully applied for the simultaneous estimation of celecoxib, erlotinib, and desmethyl erlotinib in a pharmacokinetic study in Wistar rats.