Atmospheric pressure chemical method development

A liquid chromatography-mass spectrometry (LC-MS) method that can quantitatively analyze urinar y normal and modified nucleosides in less than 30 min with a good resolution and sufficient sensitivity has been developed. Nineteen kinds of normal and modified nucleosides were determined in urine samples from 10 healthy persons and 18 breast cancer patients. Compounds were separ ated on a reverse phase Kromasil C18 column (2.1 mm I.D.) by isocratic elution mode using 20 mg/1 ammonium acetate - acetonitrile (97 3 % v/v) at 200 p.l/min. A higher sensitivity was obtained in positive atmospheric pressure chemical ionization mode APCI(-i-). 

An on-line chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI/MS/MS) methods was developed for rapid screen of pharmacokinetics of different drugs, including 5 (98RCM1216). The electron impact mass spectrum of 5 and ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7Ff-pyrido[l,2,3- fe]-l,4-benzoxazine-6-carboxylate was reported (97MI28). Electron impact/Fourier transform... 

The most recent progress in MS analysis of chlorophylls has been obtained with the development of atmospheric ionization methods such as atmospheric pressure chemical ionization (APCl) and electrospray ionization (ESI). These techniques have demonstrated much more sensitivity than thermospray ionization, detecting chloro-... 

Crescenzi et al. developed a multi-residue method for pesticides including propanil in drinking water, river water and groundwater based on SPE and LC/MS detection. The recoveries of the pesticides by this method were >80%. Santos etal. developed an on-line SPE method followed by LC/PAD and LC/MS detection in a simultaneous method for anilides and two degradation products (4-chloro-2-methylphenol and 2,4-dichlorophenol) of acidic herbicides in estuarine water samples. To determine the major degradation product of propanil, 3,4-dichloroaniline, the positive ion mode is needed for atmospheric pressure chemical ionization mass spectrometry (APCI/MS) detection. The LOD of 3,4-dichloroaniline by APCI/MS was 0.1-0.02 ng mL for 50-mL water samples. 

For confirmatory assay, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is becoming more frequently used in the analysis of OTC owing to its high sensitivity and ability. Electrospray ionization (ESI) [55-57] and atmospheric pressure chemical ionization (APCI) [41] methods combined with tandem mass spectrometry are favored because of their higher sensitivity and better reproducibility. Hamscher et al. [58] developed a method for the determination of persistent TC residues in soil fertilized with manure by HPLC tandem mass spectrometry, MS-MS, and confirmation by MS-MS-MS. Zhu et al. [59] developed an LC-tandem mass spectrometry for the analysis of common tetracyclines in water. The detection limit for oxytetracycline was 0.21 pg/L. Lykkeberg et al. [60] used LC-MS/MS for determination of oxytetracycline and its impurities EOTC, TC, ETC, ADOTC, oc-AOTC, and /i-AOTC. 

Currently no comprehensive libraries have been developed for methods, such as ESI (see Section 2.1.15) and atmospheric pressure chemical ionization (APCI see Section 2.1.8), used to ionize compounds after LC separation. Generally these types of library are user generated for a specific purpose. 

With the development of sophisticated ionization techniques including electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), HPLC-MS techniques have been successfully applied to the online analysis of ginsenosides in extracts and biological fluids (Fuzzati, 2004). In terms of sensitivity and specificity, an MS detector is better than UV or ELSD. Among the various MS methods, the HPLC-MS-MS (or just LC-MS-MS) technique is to date the most sensitive method for detection and quantification of ginsenosides. 

Musshoff et al. [35] developed a method for the enantiomeric separation of the synthetic opioid agonist tramadol and its desmethyl metabolite using a Chiralpak AD column containing amylose tris-(3,5-dimethylphenylcarbamate) as chiral selector and a n-hexane/ethanol, 97 3 v/v (5mM TEA) mobile phase nnder isocratic conditions (1 mL/min). After atmospheric pressure chemical ionization (APCI), detection was carried out in positive-ion MS-MS SRM mode. The method allowed the confirmation of diagnosis of overdose or intoxication as well as monitoring of patients compliance. 

In parallel with these developments, other techniques have been introduced that were especially applicable to the combination of liquid chromatography with MS. The most interesting, from the point of view of structural studies of flavonoid glycosides, are thermospray (TSP) and atmospheric pressure ionization (API) methods, which include electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). TSP was the first... 

The development of mass spectrometric ionization methods at atmospheric pressures (API), such as the atmospheric pressure chemical ionization (APCI)99 and the electrospray ionization mass spectrometry (ESI-MS)100 has made it possible to study liquid-phase solutions by mass spectrometry. Electrospray ionization mass spectrometry coupled to a micro-reactor was used to investigate radical cation chain reaction is solution101. The tris (p-bromophenyl)aminium hexachloro antimonate mediated [2 + 2] cycloaddition of trans-anethole to give l,2-bis(4-methoxyphenyl)-3,4-dimethylcyclobutane was investigated and the transient intermediates 9 + and 10 + were detected and characterized directly in the reacting solution. However, steady state conditions are necessary for the detection of reactive intermediates and therefore it is crucial that the reaction must not be complete at the moment of electrospray ionization to be able to detect the intermediates. 

An atmospheric pressure chemical ionization (APCI-LC-MS) (Sciex API 150 EX) method was developed for the determination of zaleplon and zolpidem in the whole blood. After single-step LLE, the hypnotics were separated by gradient-elution with an ammonium formate buffer/acetonitrile eluent on an Inertsil ODS-3 column. Methaqualone was used as IS. The recovery was higher than 70% for both hypnotics and the IS. The method was successfully applied to forensic cases [11]. 

Ephedrine and pseudoephedrine have been measured in guinea pig plasma using HPLC with fluorescence detection, following precolumn derivatization with 5-dimethylamino-napthalene-1-sulfonyl chloride in acetonitrile. The mobile phase was 0.6% phosphate buffer (pH 6.5)-methanol (3 8 v/v). Jacob et al. developed an LC-atmospheric pressure chemical ionization MS-MS method for the quantitaion of various alkaloids found in ephedra-containing dietary supplements and also in plasma and urine from subjects using these supplements. Using this method, the concentrations of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine and caffeine were determined in low nanogram quantities in plasma and urine. The analytical cycle time for this method was 12 min. 

One of the most significant developments in mass spectrometry in the recent years is the introduction of a new class of ionization methods where samples in either solid or liquid state can be directly ionized in their native environment under ambient conditions (rather than inside a mass spectrometer) without any sample preparation. This new class of ionization methods is often referred to as ambient ionization methods [1,2], Because these methods generally ionize analytes on the surface or near the surface of the samples at atmospheric pressure, they have also been called atmospheric pressure surface sampling/ionization methods or direct/open air ionization methods [3], Since the first reports on ambient ionization with desorption electrospray ionization (DESI) [4] and direct analysis in real time (DART) [5], numerous reports have been published on the applications of these new ionization methods as well as the introduction of many related ambient ionization methods such as desorption atmospheric pressure chemical ionization (DAPCI) [6], atmospheric solid analysis probe (ASAP) [7], and electrospray-assisted laser desorption/ionization (ELDI) [8], Recently, two reviews of the various established and emerging ambient ionization methods have been published [2,3],... 

Mass spectrometry (MS) has become one of the most important analytical tools employed in the analysis of pharmaceuticals. This can most likely be attributed to the availability of new instrumentation and ionization techniques that can be used to help solve difficult bioanalytical problems associated with this field (1-8). Perhaps the best illustration of this occurrence is the development of electrospray (ESI) and related atmospheric-pressure ionization (API) techniques, ion-spray (nebulizer-assisted API), turbo ionspray (thermally assisted API), and atmospheric pressure chemical ionization (APCI nebulization coupled with corona discharge), for use in drug disposition studies. The terms ESI and ionspray tend to be used interchangeably in the literature. For the purpose of this review, the term API will be used to describe both ESI and ionspray. In recent years there has been an unprecedented explosion in the use of instrumentation dedicated to API/MS (4,6,8-14). API-based ionization techniques have now become the method of choice for the analysis of pharmaceuticals and their metabolites. This has made thermospray (TSP), the predominant LC/MS technique during the 1980s, obsolete (15). Numerous reports describing the utility of API/MS for pharmaceutical analysis have appeared in the literature over the last decade (7). The... 

Kampo medicines in which A.fangchi root or A. manshuriensis stem may be misused [492], Moreover, LC-PDA and LC-EIMS detection methods both were effective in distinguishing AAI (5) and AAII (5) peaks by their spectra. Very recently, we have reported the extensive analysis of aristolochic acids and aristolactams in the various Chinese medicinal plants and crude drugs using different techniques. A method has been developed using reversed phase liquid chromatography coupled with atmospheric pressure chemical ionization (APCI) tandem mass spectrometry under the positive ion detection mode [LC/(+)APCI/MS/MS] to determine the amount of AA-1(5) in Xinxin, a traditional Chinese medicine that originate from nine Asarum species... 

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