Ion-current profiles

Figure 7.6 Total ion current profile of the acidic fraction of a sample from a linseed oil reference paint layer (Opificio delle Pietre Dure, Florence, Italy), after saponification and silylation of carboxylic and hydroxyl ic groups [9]...

LC separation applying ion chromatography in combination with ion spray mass spectrometric detection was applied for the examination of a synthetic mixture of alkyl sulfonates (CnH2n+i-SO3 re = 8) and AS with different alkyl chain lengths in the selected ion monitoring (SIM) ESI-MS(—) mode [53], Selected ion current profiles provided the separation of the compounds. The ionic matrix constituents of the eluent were removed by a suppressor module prior to MS detection to improve the signal to noise (S/N) ratio. 

Fig. 3.11. Positive-ion SRM ion current profiles for 1 (m/z 443—415 black trace), 2 (mJz 443 - 415, red trace), and 3 (m/z 345-285, blue trace) obtained during development lane scans of replicate development lanes of the RP C2 TLC separation of a mixture (50 ng each) of rhodamines 6G (1), B (2), and 123 (3) at surface scan rates of (a) 19, (b) 44, and (c) 190 jum/s using a DESI solvent (methanol) flow rate of 0.5 //Emin. Dwell time was 100 ms for each transition. Signal levels were normalized to the signal in panel (c). Chromatographic resolution, R, calculated from the data is shown in each respective panel. Reprinted with permission from G. J. Van Berkel et al. [89].

When working with non-radiolabeled drugs the major challenge is to find metabolites in the biological matrices. Because the enzymes responsible for metabolism are quite well characterized metabolic changes can partially be predicted. For example hydroxylation of the parent drug is in many cases the principal metabolic pathway. From a mass spectrometric point of view it results in an increase of 16 units in the mass spectrum. In the full-scan mode an extracted ion current profile can be used to screen for potential metabolites. In a second step a product ion spectrum is recorded for structural interpretation. Ideally, one would like to obtain relative molecular mass information and the corresponding product ion spectrum in the same LC-MS run. This information can be obtained by data dependant acquisition (DDA), as illustrated in Fig. 1.39. 

Advances in high resolution mass analyzers (TOF, FT-ICR, orbitrap) have greatly improved the detection and identification of metabolites based on accurate mass measurements. In single MS mode accurate mass determination is mainly used to differentiate between isobaric ions. Combined with LC-MS, it allows the detection of predicted metabolites by performing extracted ion current profiles... 

The analytes are determined by acquiring a full mass scan and obtaining the extracted ion current profiles (EICP) for the primary mass-to-charge ratio and at least two secondary masses of each analyte. Ions recommended for this purpose are listed in the EMSL methods. 

Figure 9. Illustration of the use of extracted ion-current profiles obtained with LC-MS, moving-belt interface, for the detection of carbamate and other pesticides. T op, extracted ion-current profile for 17 major ions second from top, extracted ion-current profile for m/z = 151 to m/z = 181 third from top, extracted ion-current profile for m/z = 86 to m/z = 305 bottom, UV absorption detection at 220 nm. (Reproduced with permission from reference 53. Copyright 1982 Preston Publications.)...

Figure 12. Total ion-current profiles obtained with LC-MS, moving-belt interface, for the detection of carbamates and other pesticides. (Reproduced with permission from reference 53. Copyright 1982 Preston Publications.)...

GC-MS runs were stored as files by the data system on discs FORTRAN routines were written to compare selected parameters in file sets and to reduce the data to summary tables for hard copy output. These routines facilitated the determination of peak areas of components in extracted ion current profiles (EICP) for both total and selected ion chromatograms, calculated the removal of components of interest (e.g., those containing halogen isotopes) by treatment processes (GAC, CI2) or derivatization, summarized the occurrence of new components of interest in treatment or derivatization, and calculated the percent of the total ion current represented by a given component. The programs allowed operator discrimination between major and minor components in a file set by preselection of an ion current threshhold for data reduction. For data summarized herein, components were >4000 ion counts, which corresponds to a level >5 of the internal standard (decachlorobiphenyl) response. 

Figure 2. GC/NICI-MS ion current profiles of secondary effluent and GAC-fUtered effluent. IS = internal standard decachlorobiphenyl.

Figure 4. GC/NICI-MS ion current profiles for 79Br and 81 Br in secondary effluent and GC-filtered effluent. Ion current ratios were as shown. Note peak labeled was not brominated (no m/z = 81).

Figure 5. GC/NICI-MS ion current profiles for 1271 in GAC secondary effluent and GAC-f titered effluent. Note peaks 1 and 4 increased after carbon contact. Both were silver labile (labeled ), whereas peaks 2 and 3 were not. The latter two components may not contain I but rather another ion of m/z = 127. Note early eluting (labeled ) components.

Figure 6. Effects of AgNC>3 on GC/NICI-MS ion current profile of secondary effluent. IS = internal standard. Peaks labeled ° in secondary effluent (GAC influent) were reduced or removed by AgNOs. Labeled peaks in bottom trace (AgNC>3 treated) were increased or created by AgNC>3...

Figure 7. Effects of AgNOs treatment on ion current profile of GAC filter effluent. IS — internal standard. Peaks labeled in untreated sample were removed or reduced by AgNO3. Peaks labeled in AgNC>3-treated sample were created or increased by the treatment.

Figure 8. Effects of AgNC>3 on GC-NICl ion current profiles of 35Cl and 37 Cl in GAC filter influent (secondary effluent) and effluent (GAC effluent). Peaks labeled in untreated effluents were reduced by AgNC>3. Peaks labeled m in AgNC>3-treated effluents were increased by Ag. (Continued on next page.)...

Figure 9. Effects of chlorination and AgN03 treatment on GAC filter effluent GC/NICI-MS ion current profiles for m/z = 35 and 79. Peaks labeled o in GAC traces were halogenated components decreased or destroyed by chlorination. Peaks labeled + in GAC-Ch traces were produced by chlorination. Peaks labeled 0 in GAC-Cfe traces were reduced by AgNQ3. Peaks labeled 0 in AgNQ3 traces were produced by AgNQ3.

Fig. 8 HPLC-fo -UV Analysis of NDMA in beer. Extracted ion current profile, in the SIM mode for NDMA-acid complex (mlz 75) and that of its dissociative photolysis products, [(CH3)2NH2]+ (mlz 46) and [(CH3)(CH2)NH]+ (mlz 44). (Reprinted with permission from Ref. 86a. Copyright 1996, American Chemical Society.)...

Figure 1.4.3 An example of extracted ion current profiles for benzene, benzene-d6, and a mixture of benzene and benzene-d6. 

Isotope ratio is measured as the ratio of the area of the primary ion of the unlabeled compound to that of the labeled compound. When the area is zero, it is assigned a value of 1. The retention times of the analytes in most cases are the same as that of their labeled analogs. The isotope can be calculated from the extracted ion current profile (EICP) areas. An example of EICP for benzene, benzene-d6, and a mixture of benzene and benzene-d6 is presented inFigure 1.4.3. Calculation to determine the RR is given below ... 

Figure 6.11 The LC/MS extracted ion current profiles for 10 combinatorial drug candidate library components, using the bioaffinity screening procedure shown in Figure 6.6. (A) Before passing through a spin column. (.B) After one cycle. (C) After two cycles. The enhancement of tight-binding ligands is evident. (Reprinted with permission from Davis et al., 1999. Copyright 1999 American Chemical Society.)...

Figure 6.33 Representative HPLC chromatograms of human serum samples for the CP-80794 SIM LC/MS assay. Extracted ion current profiles for (A) Blank (B) Blank plus internal standard (C) 0.1 ng/mL CP-80,794 (.D) 0.5 ng/mL CP-80,794. (Reprinted with permission from Fouda et al., 1991. Copyright 1991 Elsevier.)...

First of all, the isotope composition of the labeled compound is measured by recording a selected ion current profile corresponding to the molecular ions of zero-, mono-, di-, tri-, and n-labeled analog. Preferably the integration time on each channel should be adjusted in order to produce ion statis-... 

The resolution criteria must be evaluated using measurements made on the selected ion current profile (SICP) for the appropriate ions for each isomer. Measurements are not made from total ion current profiles. 

Fig. 8 Various chromatograms (from D to A mjz 170, APCI + TIC, UV at 280 nm, APCI — TIC, extracted ion current profile from APCI+) from APCI LC/MS analyses of an elastomer solvent extract.

Fig. 3 Various chromatograms (C) TIC (B) UV at 254 nm (A) m/z 722 extracted ion current profile) from the positive ion ESI LC/MS impurity profile analysis of a drug product. Note the two unknown trace level impurities in the m/z 722 extracted ion current profile.

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