Rapid quantification of amlodipine enantiomers in human plasma by LC‐MS/MS: application to a clinical pharmacokinetic study

A rapid, simple, specific and sensitive LC‐MS/MS method has been developed and validated for the enantiomeric quantification of amlodipine (AML) isomers [R‐amlodipine (R‐AML) and S‐amlodipine (S‐AML)] with 200 μL of human plasma using R‐AML‐d₄ and S‐AML‐d₄ as corresponding internal standards as per regulatory guidelines. A simple liquid–liquid extraction process was used to extract these analytes from human plasma. The total run time was 3.5 min and the elution of R‐AML, S‐AML, R‐AML‐d₄ and S‐AML‐d₄ occurred at 1.62, 2.51, 1.63 and 2.53 min, respectively. This was achieved with a mobile phase consisting of 0.2% ammonia–acetonitrile (20:80, v/v) at a flow rate of 1 mL/min on a Chiralcel OJ RH column. A linear response function was established for the range of concentrations 0.1–10 ng/mL (r >0.998) for each enantiomer. The intra‐ and inter‐day precision values for both enantiomers met the acceptance criteria. Both enantiomers were stable in a set of stability studies, viz. bench‐top, auto‐sampler, freeze–thaw cycles and long‐term. The current assay was successfully applied to a pharmacokinetic study to quantitate AML enantiomers following oral administration of 10 mg AML tablet to humans. Copyright © 2013 John Wiley & Sons, Ltd.     

Binuclear meta‐xylyl‐linked Ag(I)‐N‐heterocyclic carbene complexes of N‐alkyl/aryl‐alkyl‐substituted bis‐benzimidazolium salts: synthesis,crystal structures and in vitro anticancer studies

Salts of meta‐xylyl‐linked N‐ethyl/n‐butyl/benzyl‐substituted bis‐benzimidazolium having hexafluorophosphate counterions have been synthesized. The corresponding binuclear Ag(I)‐N‐heterocyclic carbene complexes were prepared by the reaction of Ag₂O. The N‐heterocyclic carbene (NHC) ligand precursor 7 and Ag(I)–NHC complexes 10 and 11 have been structurally characterized by single‐crystal X‐ray diffraction technique. All of the reported compounds have been tested for their anticancer activity using human colorectal (HCT 116) cancer cell lines. Sterically varied benzimidazolium salts displayed significant activity against HCT 116 cell line, yielding IC₅₀ values in the range 0.1–19.4 µ m , while Ag(I)–carbene complexes showed exceptionally good activity (0.2–1.3 µ m ) against tested cancer cell lines. Copyright © 2013 John Wiley & Sons, Ltd.     

气相色谱电子捕获检测法测定人尿中氟硝西泮的代谢物7-氨基氟硝西泮

采用气相色谱电子捕获检测法测定人尿中氟硝西泮的代谢物 7 氨基氟硝西泮。测定时尿中加入内标 7 氨基硝西泮 ,用β 葡萄糖醛酸苷酶水解及碱性液液萃取 ,再用七氟丁酸酐衍生化。尿中 7 氨基氟硝西泮提取率为 96.8% ;回收率为 98.6± 3 .4% (平均值±SD) ;检出限为 1 .2 μg L ,对口服治疗量氟硝西泮的人尿进行检测 ,可检出服药后 60h尿中的 7 氨基氟硝西泮。     

Quantification of montelukast,a selective cysteinyl leukotriene receptor (CysLT1) antagonist in human plasma by liquid chromatography–mass spectrometry: validation and its application to a human pharmacokinetic study

A highly sensitive, rapid assay method has been developed and validated for the estimation of montelukast (MTK) in human plasma with liquid chromatography coupled to tandem mass spectrometry with electro spray ionization in the positive‐ion mode. Liquid–liquid extraction was used to extract MTK and amlodipine (internal standard, IS) from human plasma. Chromatographic separation was achieved with 10 mm ammonium acetate (pH 6.4): acetonitrile (15:85, v/v) at a flow rate of 0.50 mL/min on a Discovery HS C₁₈ column with a total run time of 3.5 min. The MS/MS ion transitions monitored were 586.10 → 422.10 for MTK and 409.20 → 238.30 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.25 ng/mL and linearity was observed from 0.25 to 800 ng/mL. The intra‐day and inter‐day precisions were 5.97–8.33 and 7.09–10.13%, respectively. This novel method has been applied to a pharmacokinetic study of MTK in humans. Copyright © 2009 John Wiley & Sons, Ltd.     

Development of a liquid chromatography–isotope dilution mass spectrometry method for quantification of fentanyl in human plasma

Fentanyl is a potent analgesic drug in relieving chronic pain in patients. In this report, we present a simple, reliable and sensitive LC–ID/MS method for the quantification of fentanyl in human plasma. LC‐ID/MS analysis was carried out on a triple quadrupole mass spectrometer operated in positive electrospray ionization multiple‐reaction‐monitoring using the transitions m/z 337.6 → 187.9 for fentanyl and m/z 342.6 → 187.9 for the internal standard (D5‐fentanyl). The calibration curve covered the range 0.02–10 ng/mL. The intra‐ and inter‐batch precision were less than 6.739 and 3.126% for fentanyl and IS, with accuracy from 94.16 to 102.0%. The lower limit of quantification was identifiable and reproducible at 0.02 ng/mL. The validated method offered increased sensitivity and wide linear concentration range. This method was successfully adopted for the evaluation of bioequivalence of two fentanyl transdermal preparations after single dose administration to 20 Chinese pain‐patients. Copyright © 2009 John Wiley & Sons, Ltd.     

Marilines A–C: Novel Phthalimidines from the Sponge‐Derived Fungus Stachylidium sp.

A marine‐derived fungus of the genus Stachylidium was isolated from the sponge Callyspongia cf. C. flammea. Chemical investigation of the bioactive fungal extract led to the isolation of the novel phthalimidine derivatives marilines A₁ ( 1 a ), A₂ ( 1 b ), B ( 2 ), and C ( 3 ). The absolute configurations of the enantiomeric compounds 1 a and 1 b were assigned by a combination of experimental circular dichroism (CD) investigations and quantum chemical CD calculations. The skeleton of marilines is most unusual, and its biosynthesis is suggested to require uncommon biochemical reactions in fungal secondary metabolism. Both enantiomers, marilines A₁ ( 1 a ) and A₂ ( 1 b ), inhibited human leukocyte elastase (HLE) with an IC₅₀ value of 0.86 μM .     

Catalytic Determination of Selenium in Human Hair by Polarography Using Glutathione

Abstract

A catalytic polarographic method has been proposed for the accurate determination of selenium in human hair. This method is based on the formation of Se(0)-GSH complex in alkaline medium which gives a catalytic reduction wave in polarography. The current observed is directly proportional to the amount of selenium present. The method has been applied for the determination of selenium in human hair and the recovery of added selenium from hair is found to be 97.5 to 102%. A suitable mechanism for the reduction process involving the catalytic reduction of oxidised glutathione is proposed.     

New Enzyme Immunoassay with Visual Detection Based on Membrane Photoimmobilized Antibodies

Abstract

New method for visual enzyme immunoassay of some model antigens in solution by using covalently photoimmobilized antibodies has been developed. This approach is based on the quantitative photoimmobilization of antibodies on the surface of porous matrixes. It is easy to control the dimensions and shape of the activated zones and the quantity of the active groups on it by this technique. A strip of the membrane impregnated with p-azidobenzaldehyde was illuminated by the light. A s a result, .the quantity of aldehyde groups developed on the surface of membrane is proportional to the time of illumination. After the covalent immobilization of antibodies, the membrane has separate zones with an exact surface concentration of antibodies. The antigens of different types were assayed: human IgG, human chorionic gonadotropin, Shigella Sonnei. The lowest detection limit was 1 μg/ml, 20 U/L 1×10₄ cells/ml. The method allows measure of thyroxire concentrations in the range 50 to 200 nM, the precision of replicate measurements has the coefficient of variation 7%. The reasons for the background signal appearance were accurately analyzed. The choice of support was substantiated, the optimal conditions of it.s pretreatment being defined. This method makes possible the visualization of the results based on comparison the color intensity of zones with the control.     

Hybrid approach to the rational management of machine replacement

The paper analyzes a nonlinear integer-valued optimization problem that describes the optimal machine replacement under improving technology. The problem is extended into the classes of real-valued discrete-time optimization problems and continuous-time optimal control. The results include some qualitative properties of optimal management policies and the construction of an efficient numeric algorithm.