Determination of fendiline in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection.

A sensitive and specific method for the determination of fendiline in human plasma is presented. Fendiline was extracted from human plasma after the addition of phosphate buffer two times with 4 ml of n-hexane. The organic phase was separated and evaporated to dryness at 40 degrees C under a stream of nitrogen. The residue was dissolved and an aliquot was injected into the gas chromatograph. Chromatographic separation was performed with a DB-1 column with helium as carrier gas. Nitrogen-selective detection was performed. Quantification was performed with the signal output. The limit of detection was 1 ng/ml of plasma.     

New electron-capture gas-liquid chromatographic method for the determination of mexiletine plasma levels in man

A method for the determination of mexiletine in human plasma by gas-liquid chromatography with electron-capture detection is described. Plasma samples are extracted at pH 12 with dichloromethane after addition of the internal standard, the 2,4-methyl analogue of mexiletine. A derivative is obtained using heptafluorobutyric anhydride; according to gas chromatography-mass spectrometry it is a monoheptafluorobutyryl compound. The minimum detectable amount of mexiletine is 5 pg. Accurate determinations of human plasma levels were performed after oral or intravenous treatment.     

气相色谱-电子捕获法测定血浆中的雷公藤甲素

 血浆样品经碱化后用乙醚 氯仿 (体积比为 3∶1)混合液提取 ,浓缩的提取物与三氟醋酐进行衍生化反应 ,用气相色谱法分离、63Ni电子捕获检测器测定雷公藤甲素的含量。色谱柱为SE 5 430m× 0 2 5mmi d 交联石英毛细管柱。雷公藤甲素的质量浓度在 1 0 μg/L～ 5 0 0 μg/L范围内与峰面积线性关系良好 (r =0 9990 ) ,在血浆中的平均回收率为 96 3% ,最小检测限为 0 5 μg/L。方法重现性好 ,准确、灵敏 ,无杂质干扰 ,数据准确可靠 ,可用于临床生物样品中雷公藤甲素含量的测定。     

Optimization of a method for the determination of a mustard gas biomarker in human blood plasma by liquid chromatography–high-resolution mass spectrometry

A method for the determination of a mustard gas biomarker (an S-hydroxyethylthioethyl adduct with albumin) in blood plasma was optimized with the use of HPLC with high-resolution tandem mass-spectrometric detection. This method is based on the hydrolysis of this adduct by the proteinase K enzyme with the formation of the following stable tripeptide with cysteine, proline, and phenylalanine: S-[HETE]-Cys- Pro-Phe. The conditions of the sample preparation of human plasma artificially contaminated by mustard gas (the selection of an aliquot portion volume and an enzyme for the hydrolysis), the mass-spectrometric detection (the selection of optimum pairs of ion reactions and high-resolution detection modes), and the gradient elution program in the HPLC separation of an analyzed mixture were optimized. The detection limit of mustard gas in human blood plasma was 1 ng/mL. The approach proposed was tested in the analysis of human blood plasma samples by the standard addition technique and also within the framework of the first official biomedical test carried out by the Organization for the Prohibition of Chemical Weapons (OPCW) in 2016, and it exhibited a good accuracy, reproducibility, and specificity of determination.     

Detection of oxilofrine in plasma and urine by high-performance liquid chromatography with electrochemical detection and comparison with gas chromatography-mass spectrometry

A high-performance liquid chromatographic (HPLC) method with electrochemical detection for the determination of oxilofrine [1-(4-hydroxyphenyl)-2-methylaminopropanol] in human plasma and urine (before and after cleavage of the metabolic conjugates) is described. Isolation from biological fluids is performed batchwise by weak acid cation exchange. Separation of plasma and urine components is achieved on a reversed-phase C18 column as an ion pair with heptanesulphonic acid. For amperometric detection the potential of the electrode was set at 0.95 V versus an Ag/AgCl reference electrode. The detection limit for oxilofrine in plasma is 1 ng/ml and in urine 12.5 ng/ml at a signal-to-noise ratio of 2.0 using 1.0 ml of plasma and 0.02 ml of urine. The method was compared with a gas chromatographic-mass spectrometric method and showed a good concordance for plasma (r = 0.996) and urine (r = 0.994). With the HPLC method it is also possible to determine related sympathomimetic drugs, e.g., etilefrine, norefenefrine or octopamine, after a slight modification of the mobile phase.     

气相色谱法测定溴己新血药浓度及药代动力学研究

 建立了人血浆中溴己新的气相色谱 电子捕获测定法 ,对溴己新胶囊在健康人体内的药代动力学进行了研究。色谱柱为 5 %SE 30 (2m× 3mmi.d .)硅烷化玻璃柱。 5 氯 2 氨基二苯甲酮为内标 ,血浆样品加入磷酸盐缓冲液 (pH 6 0 )后用正己烷 二氯甲烷 (体积比为 9∶1)提取。线性范围为 1 0 μg/L～ 5 0 0 μg/L ,r =0 9994。人血浆中最小检测质量浓度为 0 5 μg/L。方法重现性好 ,日内、日间RSD分别小于 4 5 6 %和 7 11% ,平均回收率 97 5 %。 8名健康志愿者口服 8mg溴己新胶囊后 ,其体内代谢过程符合一房室模型。     

Target metabolic profiling analysis of free amino acids in plasma as EOC/TBDMS derivatives by GC-SIM-MS

Metabolic profiling analysis of free amino acids (AAs) in plasma (20 microL) was performed by gas chromatography-mass spectrometry in selected ion monitoring mode after ethoxycarbonyl/tert-butyldimethylsilyl derivatives. Characteristic fragment ions, including [M - 57](+) ions, permitted sensitive and selective detection of most of the AAs in the presence of co-extracted carboxylic acids, including free fatty acids, at much higher levels. The overall method was linear (r > or = 0.9991), reproducible (relative standard deviation = 2.3-8.8%) and accurate (relative error = -7.3-7.7%) with detection limits of 0.01-1.9 ng/mL. A total of 18 AAs, 15 protein AAs and three nonprotein AAs were quantitatively screened in a normal human plasma sample. This selective and simple method using a minimal sample volume was effective for the quantitation of plasma free AAs.     

Development of capillary zone electrophoresis-electrospray ionization-mass spectrometry for the determination of lamotrigine in human plasma

A method of coupling capillary zone electrophoresis (CZE) with electrospray ionization-mass spectrometry (ESI-MS) detection has been developed for monitoring an antiepileptic drug, lamotrigine (LTG) in human plasma. The CZE-MS was developed in three stages: (i) CZE separation and ESI-MS detection of LTG and tyramine (TRM, internal standard) were simultaneously optimized by studying the influence of CZE background electrolyte (BGE) pH, BGE ionic strength, and nebulizer pressure of the MS sprayer; (ii) sheath liquid parameters, such as pH, ionic strength, organic modifier content, and flow rate of the sheath liquid, were systematically varied under optimum CZE-MS conditions developed in the first stage; (iii) MS sprayer chamber parameters (drying gas temperature and drying gas flow rate) were varied for the best MS detection of LTG. The developed assay was finally applied for the determination of LTG in plasma samples. The linear range of LTG in plasma sample assay was between 0.1-5.0 microg/mL with a limit of detection as low as 0.05 microg/mL and run time less than 6 min. Finally, the concentration-time profile of LTG in human plasma sample was found to correlate well when CZE-ESI-MS was compared to a more established method of high-performance liquid chromatography with ultraviolet detection.     

Combination of ultrasound‐assisted ethyl chloroformate derivatization and switchable solvent liquid‐phase microextraction for the sensitive determination of l‐methionine in human plasma by GC–MS

A green and fast analytical method for the determination of l ‐methionine in human plasma is presented in this study. Preconcentration of the analyte was carried out by switchable solvent liquid phase microextraction after ethyl chloroformate derivatization reaction. Instrumental detection of the analyte was performed by means of gas chromatography–mass spectrometry. N,N‐Dimethyl benzylamine was used in the synthesis of switchable solvent. Protonated N,N‐dimethyl benzylamine volume, volume/concentration of sodium hydroxide, and vortex period were meticulously fixed to their optimum values. Besides, ethyl chloroformate, pyridine, and ethanol volumes were optimized in order to get high derivatization yield. After the optimization studies, limit of detection and quantitation values were attained as 3.30 and 11.0 ng/g, respectively, by the developed switchable solvent liquid phase microextraction gas chromatography–mass spectrometry method that corresponding to 76.7‐folds enhancement in detection power of the gas chromatography–mass spectrometry system. Applicability and accuracy of the switchable solvent liquid phase microextraction–gas chromatography–mass spectrometry method were also checked by spiking experiments. Percent recovery results were ranged from 97.8 to 100.5% showing that human plasma samples could be analyzed for its l ‐methionine level by the proposed method.     

Determination of belfosdil, a new calcium channel blocker, in human plasma by capillary gas chromatography with nitrogen-phosphorus detection

Belfosdil and the internal standard were extracted from human plasma by a double liquid-liquid extraction. After a concentration step, gas chromatographic analysis of the sample was performed using a capillary fused-silica column and a nitrogen-phosphorus detector. The limit of detection of belfosdil was 0.025 ng/ml and the standard curve was linear over the range 0.05-100 ng/ml. The intra-assay and inter-assay precisions were within 7% (relative standard deviation) and the intra-assay and inter-assay accuracy values deviated by less than 5%. The extractability of belfosdil was 79%. The assay method was successfully used for the analysis of plasma samples from clinical studies with dose ranges of 5-100 mg of belfosdil.     

Determination of conjugated linoleic acid in human plasma by fast gas chromatography

A new method for the determination of the main isomers of conjugated linoleic acid (CLA) in human and animal plasma was developed by gas chromatography coupled to flame ionization detection (GC-FID). The new method introduces three main advantages in comparison to the current available methodologies: firstly it does not require previous lipid extraction, secondly the chromatographic separation of CLA isomers was performed on an Rtx-2330 column significantly shorter and thinner than the typical long highly polar capillary columns in use that allows a faster analysis than in current methodologies, and thirdly the amount of sample needed to perform the analyses was substantially lower than the amount used in current routine methodologies. Its application to human plasma and rat plasma showed to be robust and reliable for quick and correct identification of the main CLA isomers in particular, and the total fatty acid profile in general, in routine analysis.     

Utility of nonaqueous capillary electrophoresis for the determination of lidocaine and its metabolites in human plasma: a comparison of ultraviolet and mass spectrometric detection

A nonaqueous capillary electrophoresis/electrospray mass spectrometry method for the separation of lidocaine (LID) and two of its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), has been developed. The separation medium was: 70 mM ammonium formate and 2.0 M formic acid in acetonitrile/methanol (60:40 v/v). With a sheath liquid of methanol/water (80:20 v/v) containing 2% formic acid and positive ion detection, reproducible determinations (8-11% relative standard deviation (RSD)) of lidocaine and its metabolites were performed in spiked human plasma. The limits of detection (LODs) were between 69.1 and 337 nM. The influences of sheath liquid composition, nebulizing gas pressure and drying gas temperature on the separation were examined.     

Determination of phosphoric acid triesters in human plasma using solid-phase microextraction and gas chromatography coupled to inductively coupled plasma mass spectrometry

A simple and sensitive method for determination of phosphoric acid triesters at trace levels in human plasma sample is described. In this work, solid-phase microextraction (SPME) is employed as a sample preparation procedure for extraction and pre-concentration of alkyl and aryl phosphates followed by gas chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP-MS) for phosphorus-specific and very sensitive determination of these compounds in human plasma. The detection limits from blood plasma were 50 ngL(-1) (tripropyl phosphate), 17 ngL(-1) (tributyl phosphate), 240 ngL(-1) (tris(2-chloroethyl) phosphate) and 24 ngL(-1) (triphenyl phosphate). Sample preparation involves plasma deproteinization followed by direct immersion SPME with 65 microm poly(dimethylsiloxane/divinylbenzene) fiber. Extraction was performed at 40 degrees C for 30 min and at pH 7.0 in 10 mM sodium carbonate buffer. The reported method, to our knowledge, describes the first application of SPME with element-specific detection for analysis of phosphoric acid esters. Application of the method to the plasma samples, previously stored in poly(vinyl chloride) plasma bags revealed the presence of triphenyl phosphate, which was further confirmed by SPME GC time-of-flight high-resolution mass spectrometry.     

Quantitation of hexaprazol in human plasma and urine by capillary gas chromatography with nitrogen-sensitive detection

A selective and sensitive gas chromatographic assay for hexaprazol, a new antiulcer drug, in human plasma and urine has been developed. The method involves liquid-liquid extraction and capillary gas chromatography with nitrogen-sensitive detection. The limit of quantitation of plasma hexaprazol is ca. 25 ng/ml. The assay procedure permits the measurement of the levels of the unchanged drug following its clinical administration to humans.     

Chromatographic analysis of blood lipids. Comparison between gas chromatography and thin-layer chromatography with flame ionization detection

Intact human blood plasma lipids of different composition were analyzed by gas chromatography and thin-layer chromatography with flame ionization detection. The reproducibility of the results obtained by gas and thin-layer chromatography was compared. The main advantages and disadvantages of both methods for lipid analysis are discussed. Generally, the variability of the results measured by thin-layer chromatography in series and from day to day was greater than that obtained by gas chromatography.     

Determination of oxprenolol in human plasma by high-performance liquid chromatography, in comparison with gas chromatography and gas chromatography-mass spectrometry

A high-performance liquid chromatographic method for the quantitative assay of oxprenolol in human plasma is described. After addition of alprenolol as internal standard, the compounds are extracted from plasma at alkaline pH into an organic phase and back-extracted into an acidic aqueous phase. Separation of the plasma components and metabolites was achieved on a reversed-phase column. Concentrations down to 66 nmol/l (20 ng/ml) can be determined with UV detection at 222 nm. This technique compares favourably with gas chromatographic and gas chromatographic-mass spectrometric methods.     

Determination by coupled high-performance liquid chromatography-gas chromatography of the beta-blocker levomoprolol in plasma following ophthalmic administration

Levomoprolol is a beta-blocking agent used in the topical treatment of glaucoma. The necessity for comparing the plasma levels of a drug administered by the ophthalmic route with those obtained following systemic treatment requires increasingly sensitive methods in order to determine the low plasma concentrations produced by the administration of eye drops. On-line high-performance liquid chromatography-gas chromatography and concurrent solvent evaporation proved to be advantageous in the determination of levomoprolol in human plasma. Levomoprolol was determined by capillary gas chromatography (GC) with electron-capture detection (ECD) after solid-phase extraction from plasma and derivatization. Quantitation was based on the internal standard method. The detection limit of 0.2 ng/ml is 50 times lower than that obtained with previous GC methods involving on-column injection and ECD.     

Determination of testosterone propionate in human plasma by gas chromatography-mass spectrometry

A specific, sensitive and accurate quantitative analysis of testosterone propionate in human plasma was developed using gas chromatography-mass spectrometry-selected-ion monitoring. For the calculation of testosterone propionate in plasma, peak height ratios were measured by selected-ion monitoring performed on the molecular ions of the trifluoroacetyl derivative of testosterone propionate (m/z 440) and testosterone propionate-19,19,19-d3 (m/z 443). The sensitivity of the method was judged from the lower limit of the detection of the mass spectrometer which was at 20 pg. The inter-assay coefficients of variation and relative error at a concentration of 1.31 ng/ml of plasma were 5.47% and -2.3%, respectively. The method described was applied to the determination of plasma concentrations of testosterone propionate-19,19,19-d3 following an intramuscular dose of testosterone propionate-19,19,19-d3 in a healthy male volunteer.     

Determination of Methylphosphonic Acid in Human Blood Plasma by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

Using high-performance liquid chromatography combined with tandem mass spectrometric detection, an approach has been developed for the determination of the most stable nerve agent biomarker, methylphosphonic acid, in human blood plasma. The proposed method is based on the derivatization of methylphosphonic acid with p-bromophenacyl bromide. The optimization of conditions for human plasma sample preparation, mass spectrometric detection conditions, and gradient elution program has been performed. The proposed approach has demonstrated satisfactory reproducibility and selectivity of the determination; the limit of detection for methylphosphonic acid in human plasma was 3 ng mL^–1.     

Determination of onapristone and its N-desmethyl metabolite in human plasma or serum by high-performance liquid chromatography

An automated reversed-phase high-performance liquid chromatographic method for the determination of the antiprogestin onapristone and its N-desmethyl metabolite in human plasma or serum is described. Ultraviolet detection was performed at 315 nm, with a limit of detection of 1 ng/ml at a signal-to-noise ratio of 3. The intra- and inter-assay precision were less than or equal to 6% and less than or equal to 7%, respectively. Onapristone and its N-desmethyl metabolite were stable in human plasma. The method was successfully applied to serum samples obtained from human volunteers after oral administration of onapristone.