气相色谱-质谱联用法检测保健品中的违禁药物

近年来,随着社会消费水平的不断提高,保健品市场日益兴旺,但暴露出来的问题也十分严重。假冒配方、虚假广告、任意夸大其功效作用的宣传已为社会与公众所关注,而添加违禁合成药物、假化学成分达到或增加其功效作用的行为更具隐蔽性、欺骗性和危害性,为一般消费者所难以识别。因     

X-ray and Thermal Analysis of Selected Drugs Containing Acetaminophen

Studies carried out by X-ray and thermal analysis confirmed that acetaminophen (paracetamol), declared by the manufacturers as an Active Pharmaceutical Ingredient (API), was present in all studied medicinal drugs. Positions of diffraction lines (2θ angles) of the studied drugs were consistent with standards for acetaminophen, available in the ICDD PDF database Release 2008. |Δ2θ| values were lower than 0.2°, confirming the authenticity of the studied drugs. Also, the values of interplanar distances d_hkl for the examined samples were consistent with those present in the ICDD. Presence of acetaminophen crystalising in the monoclinic system (form I) was confirmed. Various line intensities for API were observed in the obtained diffraction patterns, indicating presence of the preferred orientation of the crystallites in the examined samples. Thermal analysis of the studied substances confirmed the results obtained by X-ray analysis. Drugs containing only acetaminophen as an API have melting point close to that of pure acetaminophen. It was found that presence of other active and auxiliary substances affected the shapes and positions of endothermal peaks significantly. A broadening of endothermal peaks and their shift towards lower temperatures were observed accompanying an increase in the contents of additional substances being “impurities” in relation to the API. The results obtained by a combination of the two methods, X-ray powder diffraction (XRPD) and differential scanning calorimetry/thermogravimetry (DSC/TGA), may be useful in determination of abnormalities which can occur in pharmaceutical preparations, e.g., for distinguishing original drugs and forged products, detection of the presence of a proper polymorphic form or too low content of the active substance in the investigated drug.     

Differential Pulse Voltammetric Simultaneous Determination of Four Anti‐Inflammatory Drugs by Using Soft Modelling

An application of a partial least squares calibration method for the simultaneous voltammetric determination of indomethacin, acemethacin, piroxicam and tenoxicam is suggested. It was shown that it is possible to resolve complex mixtures of analytes even when they have strongly overlapped signals. In order to check the proposed method, statistical analysis of the results was performed by mean of hypothesis tests. The method developed was applied to the electrochemical reduction region of four anti‐inflammatory drugs and allowed the drugs to be quantified at concentrations between 0.52 and 4.09 μg mL^?1 for acemethacin, 0.44 and 3.50 μg mL^?1 for indomethacin, 0.43 and 3.40 μg mL^?1 for piroxicam, and 0.42 and 3.30 μg mL^?1 for tenoxicam with good results. The average absolute value of relative errors was 2.25%, 4.31%, 1.68% and 2.49%, respectively.     

Anticancer Drugs ( Ⅳ )——New Derivatives of Podophyllotoxin

Four new derivatives of podophyllotoxin, N'-podophyllic acid-N-[3-(2, 2, 5, 5-te-tramethyl-pyrrolinenyloxy)] semicarbazide(GP-11, 6), podophyllic acid [3-(2,2,5,5-te-tramethyl-pyrrolinenyloxy)]hydrazone (GP-12, 7), podophyllic acid-[4-(2, 2, 6, 6-tetramethyl-1-hydroxy piperidine)]hydrazone(GP-1-OH, 8) and podophyllic acid[4-(2,2, 6, 6-tetramethyl piperidine)]hydrazone(GP-1-H, 9) were synthesized. The inhibition effect of the four new compounds on L-1210 cells were determined. The antitumor activity and toxicity of GP-1(2), GP-1-OH(8), GP-1-H(9) and VP-16-213(1) were discussed.     

Glutathione modified CdTe quantum dots as a label for studying DNA interactions with platinum based cytostatics

Cisplatin, carboplatin, and oxaliplatin represent three generations of platinum based drugs applied successfully for cancer treatment. As a consequence of the employment of platinum based cytostatics in the cancer treatment, it became necessary to study the mechanism of their action. Current accepted opinion is the formation of Pt‐DNA adducts, but the mechanism of their formation is still unclear. Nanomaterials, as a progressively developing branch, can offer a tool for studying the interactions of these drugs with DNA. In this study, fluorescent CdTe quantum dots (QDs, λ_em = 525 nm) were employed to investigate the interactions of platinum cytostatics (cisplatin, carboplatin, and oxaliplatin) with DNA fragment (500 bp, c = 25 μg/mL). Primarily, the fluorescent behavior of QDs in the presence of platinum cytostatics was monitored and major differences in the interaction of QDs with tested drugs were observed. It was found that the presence of carboplatin (c = 0.25 mg/mL) had no significant influence on QDs fluorescence; however cisplatin and oxaliplatin quenched the fluorescence significantly (average decrease of 20%) at the same concentration. Subsequently, the amount of platinum incorporated in DNA was determined by QDs fluorescence quenching. Best results were reached using oxaliplatin (9.4% quenching). Linear trend (R² = 0.9811) was observed for DNA platinated by three different concentrations of oxaliplatin (0.250, 0.125, and 0.063 mg/mL). Correlation with differential pulse voltammetric measurements provided linear trend (R² = 0.9511). As a conclusion, especially in the case of oxaliplatin‐DNA adducts, the quenching was the most significant compared to cisplatin and nonquenching carboplatin.     

Präparation polykristalliner LiF-Speicherphosphore für die Thermolumineszenzdosimetrie

Zur Ausbildung eines intensiven Glowmaximums der Thermolumineszenz bei 200°C wurden eine Vielzahl von Kationen auf ihre Aktivatorwirkung gegenüber LiF untersucht. Als günstige Aktivatoren erwiesen sich bei der Herstellung des LiF mitgefällte Mg-, Ca- und Ti-Spuren. Die Eigenscaften der präparierten Phosphore werden mit den Analysenergebnissen verglichen und diskutiert.     

Chiral separation and molecular simulation study of six antihistamine agents on a coated cellulose tri-(3,5-dimethylphenycarbamate) column (Chiralcel OD-RH) and its recognition mechanisms

Enantiomeric separation of six antihistamine agents was first systematically investigated on a cellulose-based chiral stationary phase (CSP), that is, cellulose tris-(3,5-dimethyl phenyl carbamate) (Chiralcel OD-RH), under the reversed-phase mode. Orphenadrine, meclizine, terfenadine, dioxopromethazine, and carbinoxamine enantiomers were completely separated under the optimized mobile phase conditions with resolutions of 5.02, 1.93, 1.68, 1.67, and 1.54, respectively. Mequitazine was partially separated with a resolution of 0.77. The influences of type and concentration of buffer salt, the pH of buffer solution, and the type and ratio of organic modifier on the chiral separation were evaluated and optimized. For a better insight into the enantiorecognition mechanisms, molecular docking was carried out via the Autodock software. The lowest binding energy and the optimal conformations of the analytes/CSP complexes were supplied, and the mechanisms of chiral recognition were determined. According to the results, the key interactions for the chiral recognition of these six analytes on CDMPC were π–π interactions, hydrophobic interactions, hydrogen bond interactions, and some special interactions.     

Identification and quantification of the antipsychotics risperidone,aripiprazole, pipamperone and their major metabolites in plasma using ultra‐high performance liquid chromatography–mass spectrometry

The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra‐high performance liquid chromatography–mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra‐high performance liquid chromatography–mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed‐phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli‐Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 μL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9‐OH‐risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run‐time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis of New Tandospirone Analogues Carrying 1-(3-(Trifluoromethyl)phenyl)piperazine

New tandospirone analogues containing a 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) moiety have been synthesized by hydroarylation reactions with Pd(OAc)₂. The perhydroisoindole derivatives were obtained by the reaction of reduced starting material with aryl-(heteroaryl) iodides under the same conditions. Spiro-1,3-indandionolylpyrrolidine derivatives having an array of stereocenters are reported.     

Schistosomiasis Chemotherapy

After malaria, schistosomiasis (or bilharzia) is the second most prevalent disease in Africa, and is occurring in over 70 countries in tropical and subtropical regions. It is estimated that 600 million people are at risk of infection, 200 million people are infected, and at least 200 000 deaths per year are associated with the disease. All schistosome species are transmitted through contact with fresh water that is infested with free‐swimming forms of the parasite, which is known as cercariae and produced by snails. When located in the blood vessels of the host, larval and adult schistosomes digest red cells to acquire amino acids for growth and development. Vaccine candidates have been unsuccessful up to now. Against such devastating parasitic disease, the antischistosomal arsenal is currently limited to a single drug, praziquantel, which has been used for more than 35 years. Because the question of the reduction of the activity of praziquantel was raised recently, it is thus urgent to create new and safe antischistosomal drugs that should be combined with praziquantel to develop efficient bitherapies.