Application of selected ion flow tube mass spectrometry to real‐time atmospheric monitoring

Data are presented for real‐time atmospheric monitoring of volatile organic chemicals (VOCs) in air using selected ion flow tube mass spectrometry (SIFT‐MS) technology. These measurements were made by one of the new generation of SIFT‐MS instruments. Results are shown for five VOCs that were continually monitored from a stationary sampling point over a 4‐day period: ethene, ethanol, 1,3‐butadiene, benzene and toluene. All analytes except ethene in the study have at least two simultaneous and independent measures of concentration. These results demonstrate the great advances in SIFT‐MS that have been made in recent years. 1,3‐Butadiene is measured at a concentration of 9 pptv with a precision of 44%. For a 1‐s integration time, a detection limit of 50 pptv is achieved. Instrument sensitivities are reported for all five analytes. Copyright © 2010 John Wiley & Sons, Ltd.     

Separation of xanthines in hydro‐organic and polar‐organic elution modes on a titania stationary phase

Hydrophilic interaction LC was investigated in hydro‐organic and nonaqueous elution modes on a titania column by using a set of N‐methyl xanthines as neutral polar probes. To get information regarding the mechanisms that are behind the discrimination of these analytes in hydrophilic interaction, we focused our study on the type and amount of organic modifier as a critical yet rarely explored mobile phase parameter. Several alcohols such as methanol, ethanol, and isopropanol were studied as substitutes to acetonitrile in hydro‐organic elution mode. Compared to silica, the investigation of the eluotropic series of these alcohols on titania highlighted a different implication in the retention mechanism of the xanthine derivatives. At low amounts of protic solvents, the adsorption mainly characterized the retention of analytes on bare silica; whereas mixed interactions including adsorption and ligand exchange were identified on native titania. To investigate the peculiar behavior of alcohols on the metal oxide, methanol, ethanol, and ethylene glycol were tested in replacement of water in polar‐organic elution mode. Distinctive effects on the chromatographic retention and selectivity of xanthines were noticed for the dihydric alcohol, which was found to be a stronger eluting component than water on titania.     

Linear and nonlinear free energy relationships in nucleophilic substitution reaction of 2‐bromo‐5‐nitrothiophene with morpholine

The reaction of 2‐bromo‐5‐nitrothiophene with morpholine was studied as an aromatic nucleophilic substitution reaction in various compositions of methanol with ethyl acetate and aqueous solution of methanol, ethanol, and propane‐2‐ol at 25°C. The second‐order rate coefficients of the reaction were spectrophotometerically determined. It was shown that a mounting trend with the mole fraction of water in aqueous solution of alcohols and a mild decreasing with the mole fraction of ethyl acetate in methanol–ethyl acetate mixtures. Solvent effect investigations based on linear free energy relationship (LFER) confirm that polarity has a major effect, whereas the hydrogen‐bond donor and acceptor abilities of the media have a minor effect on the reaction rate. A nonlinear free energy relationship based on preferential solvation hypothesis showed differences between the microsphere solvation of the solute and the bulk composition of the solvents, and nonideal behavior was observed in the trend of rate coefficients, which was consistent with LFER results. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 45: 59–67, 2013     

Syndiotactic‐ and heterotactic‐specific radical polymerizations of N‐n‐propyl‐α‐fluoroacrylamide and phase‐transition behaviors of aqueous solutions of poly(N‐n‐propyl‐α‐fluoroacrylamide)

Radical polymerization of N‐n‐propyl‐α‐fluoroacrylamide (NNPFAAm) was investigated in several solvents at low temperatures in the presence or absence of Lewis bases, Lewis acids, alkyl alcohols, silyl alcohols, or fluorinated alcohols. Different effects of solvents and additives on stereospecificity were observed in the radical polymerizations of NNPFAAm and its hydrocarbon analogs such as N‐isopropylacrylamide (NIPAAm) and N‐n‐propylacrylamide (NNPAAm); for instance, syndiotactic (and heterotactic) specificities were induced in radical polymerization of NNPFAAm in polar solvents (and in toluene in the presence of alkyl and silyl alcohols), whereas isotactic (and syndiotactic) specificities were induced in radical polymerizations of the hydrocarbon analogs under the corresponding conditions. In contrast, heterotactic specificity induced by fluorinated alcohols was further enhanced in radical polymerization of NNPFAAm. The effects of stereoregularity on the phase‐transition behaviors of aqueous solutions of poly(NNPFAAm) were also investigated. Different tendencies in stereoregularity were observed in aqueous solutions of poly(NNPFAAm)s from those in solutions of the hydrocarbon analogs such as poly(NIPAAm) and poly (NNPAAm). The polymerization behavior of NNPFAAm and the phase‐transition behavior of aqueous poly(NNPFAAm) are discussed based on possible fluorine–fluorine repulsion between the monomer and propagating chain‐end, and neighboring monomeric units. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Effects of addition of short-chain alcohol solvents on micellization and thermodynamic properties of anionic surfactants sodium dodecyl sulfate and sodium dodecyl sulfonate in aqueous solutions

Micellar and thermodynamic properties of anionic surfactants sodium dodecyl sulfate (SDS) and sodium dodecyl sulfonate (SDSn) in aqueous solutions of 5 wt% short-chain alcohols methanol, ethanol, and 1-butanol were investigated by experimental electrical conductivities, densities and sound velocities at 298.15 K. It was found that methanol behaves like a cosolvent and increases the critical micelle concentration (CMC) of both surfactants in aqueous solutions. However, the other investigated alkanols act as a cosurfactant and decrease the CMC by their presence. The values of the degree of counterion association on the micelles of both surfactants in aqueous methanol solution are same as those in pure water, and they decrease with increasing the alkyl chain length of alcohol. Furthermore, the values of the apparent molar volume and isentropic compressibility of the monomeric and micellar forms of the investigated surfactants were obtained from the experimental density and sound velocity data. It was found that the values of the apparent molar properties of both micellar and monomeric forms of the studied surfactants increase by increasing the alkyl chain of the alcohols.     

Application of a sensitive and specific LC‐MS/MS method for determination of eriodictyol‐8‐C‐β‐d‐glucopyranoside in rat plasma for a bioavailability study

This study is the first to detail the development and validation of a rapid, sensitive and specific LC‐ESI‐MS/MS method for the determination of eriodictyol‐8‐C‐β‐d ‐glucopyranoside (EG) in rat plasma. A simple protein precipitation method was used for plasma sample preparation. Chromatographic separation was successfully achieved on an Agilent Zorbax XDB C₁₈ column (2.1 × 50 mm, 3.5 µm) using a step gradient program with the mobile phase of 0.1% formic acid aqueous solution and acetonitrile with 0.1% formic acid. EG and the internal standard (IS) were detected using an electrospray negative ionization mass spectrometry in the multiple reaction monitoring mode. This method demonstrated good linearity and did not show any endogenous interference with the active compound and IS peaks. The lower limit of quantification of EG was 0.20 ng/mL in 50 μL rat plasma. The average recoveries of EG and IS from rat plasma were both above 80%. The inter‐day precisions (relative standard deviation) of EG determined over 5 days were all within 15%. The present method was successfully applied to a quantification and bioavailability study of EG in rats after intravenous and oral administration. The oral absolute bioavailability of EG in rats was estimated to be 7.71 ± 1.52%. Copyright © 2014 John Wiley & Sons, Ltd.     

The development and validation of a high‐throughput LC–MS/MS method for the analysis of endogenous β‐hydroxy‐β‐methylbutyrate in human plasma

A high‐throughput, sensitive, and rugged liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the rapid quantitation of β ‐hydroxy‐β ‐methylbutyrate (HMB) in human plasma has been developed and validated for routine use. The method uses 100 μL of plasma sample and employs protein precipitation with 0.1% formic acid in methanol for the extraction of HMB from plasma. Sample extracts were analyzed using LC–MS/MS technique under negative mode electrospray ionization conditions. A ¹³C–labeled stable isotope internal standard was used to achieve accurate quantitation. Multiday validation was conducted for precision, accuracy, linearity, selectivity, matrix effect, dilution integrity (2×), extraction recovery, freeze–thaw sample stability (three cycles), benchtop sample stability (6 h and 50 min), autosampler stability (27 h) and frozen storage sample stability (146 days). Linearity was demonstrated between 10 and 500 ng/mL. Inter‐day accuracies and coefficients of variation (CV) were 91.2–98.1 and 3.7–7.8%, respectively. The validated method was proven to be rugged for routine use to quantify endogenous levels of HMB in human plasma obtained from healthy volunteers.     

Effect of Different Solvent Characteristics on the Proton‐Ligand and Sm+3‐Ligand Formation Constant of Butanamide‐3‐[2‐[(2‐Hydroxyphenyl Methylene) Amino]Ethylimino]N‐Phenyl(BHPAP) in Mixed Solvents

Complexes equilibrium of (BHPAP) with proton and Sm⁺³ ion has been measured in various mixed aqueous solvents, viz.; methanol‐water, ethanol‐water, acetone‐water and dioxane‐water. Based on potentiometric equilibrium measurements of hydrogen ion concentration at 30 °C, ionic strength 0.1 M KNO₃ and in the above various mixed solvents, the values of protonation constant of BHPAP‐Sm⁺³ complex have been evaluated. The variation of protonation and stability constants with the inverse of dielectric constant or mole fraction of solvent was studied. Application of Fuoss expression and consideration of electrostatic and non‐electrostatic effects are made to explain the above constants. The solid complexes were isolated for each Pr⁺³ and Nd⁺³‐BHPAP. Elemental analysis, conductance, infrared spectra, and electronic spectra for these solutions and TG, DTG and DTA measurements characterized these solids. The ligand behaves towards the metal ion as a dibasic tetradentate ligand.     

Enantioseparation tuned by solvent polarity on a β‐cyclodextrin clicked chiral stationary phase

The efficient enantioseparation of 26 racemates has been achieved with the perphenylcarbamoylated cyclodextrin clicked chiral stationary phase by screening the optimum composition of mobile phase in high‐performance liquid chromatography. The chromatographic results indicate that both the retention and chiral resolution of racemates are closely related to the polarity of the mobile phases and the structures of analytes. The addition of alcohols can significantly tune the enantioseparation in normal‐phase high‐performance liquid chromatography. The addition of methanol and the ratio of ethanol/methanol or isopropanol/methanol played a key role on the resolution of flavonoids in ternary eluent systems. The chiral separation of flavonoids with pure organic solvent as mobile phase indicates the preferential order for chiral resolution is methanol>ethanol>isopropanol>n‐propanol>acetonitrile.     

Dual‐parameter correlations on rate of an aromatic nucleophilic substitution reaction in aqueous solutions of methanol,ethanol, and propan‐2‐ol

Reaction kinetics of 1‐chloro‐2,4‐dinitrobenzene with piperidine was studied spectrophotometrically in aqueous solutions of methanol, ethanol, and propan‐2‐ol at 25°C. The reaction in these solutions is not catalyzed by piperidine. The plots of second‐order rate constants of the reaction vs. mole fraction of water show maxima in the all‐aqueous solutions. Single‐parameter correlations of log k₂ vs. π* (dipolarity/polarizability), α (hydrogen‐bond donor acidity), and E_T^N (normalized polarity parameter) are very poor in the all solutions (for example, in aqueous solutions of ethanol, regression coefficients are 0.814, 0.113, and 0.486, respectively). Dual‐parameter correlations of log k₂ vs. π* and α in all cases represent significant improvement with regard to the single‐parameter models (in aqueous solutions of ethanol: n = 11, r = 0.980, and s = 0.034). Dipolarity/polarizability and hydrogen‐bond donor acidity (HBD) of media have opposite effects on the reaction rate. The activated complex leading to the zwitterionic intermediate is expected to be favored by increasing the solvent dipolarity/polarizability parameter. Increasing the hydrogen‐bond donor acidity of solvent stabilizes piperidine and hence the reaction rate decreases. A dual‐parameter equation of log k₂ vs. π* and α was obtained in the all‐aqueous solutions (n = 31, r = 0.956, s = 0.055) in which π* and α have approximately equal and opposite effects on the reaction rate. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 118–123, 2001     

Quantitation and pharmacokinetics of 1,4‐diamino‐2,3‐dicyano‐1,4‐bis (2‐aminophenylthio) butadiene (U0126) in rat plasma by liquid chromatography‐tandem mass spectrometry

A simple, robust, and rapid LC‐MS/MS method was developed for the quantitation of U0126 and validated in rat plasma. Plasma samples (20 μL) were deproteinized using 200 μL ACN containing 30 ng/mL of chlorpropamide, internal standard. Chromatographic separation performed on an Agilent Poroshell 120 EC‐C₁₈ column (4.6 × 50 mm, 2.7 μm particle size) with an isocratic mobile phase consisting of a 70:30 v/v mixture of ACN and 0.1% aqueous formic acid. Each sample was run at 0.6 mL/min for a total run time of 2 min per sample. Detection and quantification were performed using a mass spectrometer in selected reaction‐monitoring mode with positive ESI at m/z 381 → 123.9 for U0126 and m/z 277 → 175 for the internal standard. The standard curve was linear over a concentration range of 20–5000 ng/mL with correlation coefficients greater than 0.9965. Precision, both intra‐ and interday, was less than 10.1% with an accuracy of 90.7–99.4%. No matrix effects were observed. U0126 in rat plasma degraded approximately 41.3% after 3‐h storage at room temperature. To prevent degradation, sample handling should be on an ice bath and all solutions kept at 4°C. This method was successfully applied to a pharmacokinetic study of U0126 at various doses in rats.     

Solute–solvent interaction effects on second‐order rate constants of reaction between 1‐chloro‐2,4‐dinitrobenzene and aniline in alcohol–water mixtures

The second‐order rate coefficients for aromatic nucleophilic substitution reaction between 1‐chloro‐2,4‐dinitrobenzene and aniline have been measured in aqueous solutions of ethanol and methanol at 25°C. The plots of rate constants versus mole fraction of water show a maximum in all‐aqueous solutions. The effect of four empirical solvent parameters including hydrogen bond donor acidity (α) dipolarity/polarizability (π^*) normalized polarity (E^N_T) and solvophobicity (Sp) has been investigated. This investigation has been carried out by means of simple and multiple regression models. A dual‐parameter equation of log k₂ versus Sp and α was obtained in all‐aqueous solutions (n = 41, r = 0.962, s = 0.053, p = 0.0000). This equation shows that solvophobicity and hydrogen bond donor acidity are important factors in the occurrence of the reaction and they have opposite effects on reaction rate. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 37: 90–97, 2005     

Comparative pharmacokinetic study of four major bioactive components after oral administration of Zhi‐Zi‐Hou‐Po decoction in normal and corticosterone‐induced depressive rats

A highly selective and efficient LC–MS/MS method was developed to determine the plasma concentration of magnolol, hesperidin, neohesperidin and geniposide following oral administration of Zhi‐Zi‐Hou‐Po decoction in normal and depressed rats. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was performed on an XTerra^® MS C₁₈ column using a gradient elution with a mobile phase composed of acetonitrile–0.1% aqueous formic acid. The proposed method was validated to be specific, accurate and precise for the analytes determination in plasma samples. The calibration curves displayed good linearity over definite concentration ranges for the analytes. The intra‐ and inter‐day precision of the proposed method at three different levels were all within <11.13% and the relative errors ranged from ?8.46 to 8.93%. The recovery of the four compounds ranged from 82.72 to 89.08% and no apparent matrix effect was observed during sample analysis. After full validation, the established method was successfully applied for comparing the pharmacokinetics of four components between normal and depressed rats. The results showed that the AUC and C_max of four analytes in depressed rats were significantly different from those in normal rats and might provide helpful information to guide the clinical use of Zhi‐Zi‐Hou‐Po to treat depression.     

Ultrafast SET‐LRP of methyl acrylate at 25 °C in alcohols

Alcohols are known to promote the disproportionation of Cu(I)X species into nascent Cu(0) and Cu(II)X. Therefore, alcohols are expected to be excellent solvents that facilitate the single‐electron transfer mediated living radical polymerization (SET‐LRP) mediated by nascent Cu(0) species. This publication demonstrates the ultrafast SET‐LRP of methyl acrylate initiated with bis(2‐bromopropionyloxy)ethane and catalyzed by Cu(0)/Me₆‐TREN in methanol, ethanol, 1‐propanol, and tert‐butanol and in their mixture with water at 25 °C. The structural analysis of the resulting polymers by a combination of ¹H NMR and MALDI‐TOF MS demonstrates the synthesis of perfectly bifunctional α,ω‐dibromo poly(methyl acrylate)s by SET‐LRP in alcohols. Moreover, this work provides an expansion of the list of solvents available for SET‐LRP. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2745–2754, 2008     

Comparison of multiple API techniques for the simultaneous detection of microconstituents in water by on‐line SPE‐LC‐MS/MS

This study described a fully automated method using on‐line solid phase extraction of large volume injections coupled with high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) to simultaneously detect a group of recalcitrant microconstituents (pharmaceuticals and personal care products, steroid hormones and sterols) in aqueous matrices. Samples (1 mL to 20 mL) were loaded to the preconcentration column at 1 mL/min, and the column was washed with 1000 μL of 25% methanol in LC/MS water to remove polar and ionic interferences before LC‐MS/MS analysis. Three different atmospheric pressure ionization (API) techniques, including photoionization (APPI) with four different dopants (acetone, anisole, chlorobenzene and toluene), heated electrospray ionization (HESI) and atmospheric pressure chemical ionization (APCI), were evaluated on the basis of method detection limits (MDLs) and recoveries from different aqueous matrixes. Results indicated that APPI with toluene as dopant was the most sensitive ionization method for the majority of the analytes. When using 5 mL of sample, MDLs for pharmaceuticals and personal care products, including carbamazepine, DEET, caffeine, naproxen, acetaminophen and primidone, were between 0.3 ng/L and 15 ng/L. MDLs of hormones, including testosterone, equilenin, progesterone, equilin, 17β‐estradiol, 17α‐ethynylestradiol, estrone, androsterone, mestranol and estriol, were between 1.2 ng/L and 37 ng/L. The combination of APPI with dopant allowed the detection of two difficult to ionize fecal related sterols, such as coprostan‐3‐ol and coprostan‐3‐one with MDLs of 5.4 ng/L and 11 ng/L, respectively. Calculated MDLs are more than adequate for analysis of wastewater using 1 to 5 mL sample size and for surface waters using up to 20 mL sample size. Copyright © 2012 John Wiley & Sons, Ltd.     

Validated assay for the simultaneous quantification of total vincristine and actinomycin‐D concentrations in human EDTA plasma and of vincristine concentrations in human plasma ultrafiltrate by high‐performance liquid chromatography coupled with tandem mass spectrometry

A sensitive, specific and efficient high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay for the simultaneous determination of total vincristine and actinomycin‐D concentrations in human plasma and an assay for the determination of unbound vincristine are presented. Electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and heated electrospray ionization (H‐ESI) were tested as ionization interfaces. For reasons of robustness ESI was chosen followed by tandem mass spectrometry (ESI‐MS/MS). For the plasma assay a 30 µL aliquot was protein precipitated with acetonitrile/methanol (50:50, v/v) containing the internal standard vinorelbine and 10 µL volumes were injected onto the HPLC system. To determine unbound vincristine, ultrafiltrate was produced from plasma using 30 kDa centrifugal filter units. The plasma ultrafiltrate was mixed with methanol (50:50, v/v), internal standard vinorelbine was added and 20 µL aliquots were injected onto the HPLC system. Separation was achieved on a 50 × 2.1 mm i.d. Xbridge C₁₈ column using 1 mM ammonium acetate/acetonitrile (30:70, v/v) adjusted to pH 10.5 with ammonia, run in a gradient with methanol at a flow rate of 0.4 mL/min. HPLC run time was 6 min. The assay quantifies in plasma vincristine from 0.25 to 100 ng/mL and actinomycin‐D from 0.5 to 250 ng/mL using plasma sample volumes of only 30 µL. Vincristine in plasma ultrafiltrate can be quantified from 1 to 100 ng/mL. Validation results demonstrate that vincristine and actinomycin‐D can be accurately and precisely quantified in human plasma and plasma ultrafiltrate with the presented methods. The assays are now in use to support clinical pharmacological studies in children treated with vincristine and actinomycin‐D. Copyright © 2009 John Wiley & Sons, Ltd.     

Electrochemical Determination of D‐Glucose Using Nortropine‐N‐oxyl under Physiological Conditions

Nortropine‐N‐oxyl (NNO) was synthesized in a single step from nortropine. The electrocatalytical activity of NNO was evaluated by cyclic voltammetry in pH7.0 phosphate buffer solution. The anodic peak current for ethanol, isopropanol and glucose was enhanced, showing these alcohols were oxidized by electrocatalytic effect of NNO. On the other hand, TEMPO derivative (4‐hydroxy‐2,2,6,6,‐terramethylpiperidine N‐oxyl free radical) could not oxidize the alcohols under the same condition. The electrochemical response of the NNO to glucose was investigated. The anodic peak current increased with an increase in the concentration of glucose. A linear response to the glucose concentration ranging from 0.1 to 10 mM was obtained.     

A kinetic method to estimate dissociation degrees of micellar aggregates in TTAB–alcohol aqueous micellar solutions

The reactions of dehydrochlorination of 1,1‐trichloro‐2,2‐bis(p‐chlorophenyl)ethane, DDT, and 1,1‐dichloro‐2,2‐bis(p‐chlorophenyl)ethane, DDD, with hydroxide ions were studied in various TTAB–alcohol (TTAB = tetradecyltrimethylammonium bromide) aqueous micellar solutions as a function of alcohol content. The alcohols used were heptanol, hexanol, pentanol, butanol, isobutanol, tert butanol, propanol and isopropanol. Kinetic data show that the dissociation degree of the micelles is the main factor controlling reactivity in all the TTAB–alcohol micellar solutions. This fact permits the development of a kinetic method in order to estimate the dissociation degree of the micellar aggregates present in the alcohol–TTAB aqueous micellar solutions. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 204–209, 2000     

Nonvolatile salt‐free stabilizer for the quantification of polar imipenem and cilastatin in human plasma using hydrophilic interaction chromatography/quadrupole mass spectrometry with contamination sensitive off‐axis electrospray

A hydrophilic interaction chromatography/mass spectrometry (HILIC‐MS)‐based assay for imipenem (IMP) and cilastatin (CIL) was recently reported. This orthogonal electrospray ion source‐based (ORS) assay utilized nonvolatile salt (unremovable) to stabilize IMI in plasma. Unfortunately, this method was not applicable to conventional MS with off‐axis spray (OAS‐MS) because MS sensitivity was rapidly deteriorated by the nonvolatile salt. Therefore, we aimed to find a nonvolatile salt‐ and ion suppression‐free approach to stabilize and measure the analytes in plasma using OAS‐MS. Acetonitrile and methanol were tested to stabilize the analytes in the plasma samples. The recoveries, matrix effects and stabilities of the analytes in the stabilizer‐treated samples were studied. The variations in MS signal intensities were used as the indicator of the assay ruggedness. The results show that a mixture of methanol and acetonitrile (1:1) is best for the storage and measurement of IMP and CIL in human plasma. Utilization of this precipitant not only blocked the hydrolysis of the analytes in plasma but also resulted in an ion suppression‐free, fast (120 s per sample) and sensitive detection. The sensitivity obtained using the less sensitive OAS‐MS (API3000, 4 pg on column) is much greater than that of the published ORS‐MS‐based assay (API4000, 77 pg on column). The ruggedness of the assay was demonstrated by its constant MS signal intensity. In conclusion, an improved HILIC/MS‐based assay for IMP and CIL was established. The approach presented here provides a simple solution to the challenge of analyzing hydrolytically unstable β‐lactam antibiotics in biological samples. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of a novel paclitaxel derivative (NPD‐103) in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry

A sensitive and specific ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS‐MS) method for quantification of a newly developed anticancer agent NPD‐103 has been established. An aliquot of human plasma sample (200 µL) was spiked with ¹³C‐labeled paclitaxel (internal standard) and extracted with 1.3 mL of tert‐butyl methyl ether. NPD‐103 was quantitated on a C₁₈ column with methanol–0.1% formic acid (75:25, v/v) as mobile phase using UPLC‐MS‐MS operating in positive electrospray ionization mode with a total run time of 3.0 min. For NPD‐103 at the concentrations of 1.0, 5.0 and 10.0 µg/mL in human plasma, the absolute extraction recoveries were 95.58, 102.43 and 97.77%, respectively. The linear quantification range of the method was 0.1–20.0 µg/mL in human plasma with linear correlation coefficients greater than 0.999. The intra‐ and inter‐day accuracy for NPD‐103 at 1.0, 5.0 and 10.0 µg/mL levels in human plasma fell into the ranges of 95.29–100.00% and 91.04–94.21%, and the intra‐ and inter‐day precisions were in the ranges of 8.96–11.79% and 7.25–10.63%, respectively. This assay is applied to determination of half‐life of NPD‐103 in human plasma. Copyright © 2008 John Wiley & Sons, Ltd.