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Ionized calcium concentration in maintenance hemodialysis patients.

Since numerous formulae for "adjusted" total calcium and "calculated" ionized calcium are used in clinical practice, serum total and ionised calcium concentrations were measured in 20 hemodialysis patients with a wide range of serum total calcium and albumin concentrations. Patients were evaluated pre- and post-dialysis to document the effect of pH. Pre-dialysis total calcium varied from 1.70 to 3.17 mmol/L (mean 2.52 +/- 0.08) and a very close correlation between total and ionized calcium was found (r = 0.842; p less than 0.001) with 50.2% being in the ionized form. Dialysis did not alter this relationship despite a significant increase in pH (0.09; p less than 0.01). A normal volunteer group also demonstrated a similar correlation between total and ionized calcium and while the non-ionized calcium concentration was positively and significantly correlated to the serum albumin concentration (r = 0.629; p less than 0.01) this was not the case in the dialysis patients, although the serum albumin range was much greater (18 to 46 g/L). These results suggest that the percentage of total calcium in the ionized form in dialysis patients is not different from the normal population and that minor changes in pH and albumin may not be as important as has previously been believed. While direct measurement is preferable, halving of the total calcium is a simple prediction of the ionized fraction.

Calcium↗

Ionized magnesium in gestational diabetes.

A longitudinal prospective study was performed in order to describe variations in ionized magnesium in patients with gestational diabetes. Twenty-two gestational diabetic women and 24 healthy pregnant women were included consecutively. Blood samples were obtained in the second and third trimester and 2 days postpartum in both groups. The blood samples were analysed for serum ionized magnesium, serum ionized calcium and pH. None of the groups demonstrated any time-related changes in ionized magnesium. However, in the third trimester the level of ionized magnesium was statistically significantly elevated in patients with gestational diabetes compared to controls (0.57 +/- 0.05 mmol/l vs. 0.51 +/- 0.06 mmol/l; p < 0.01). The level of ionized calcium remained stable throughout the study period in both groups. In conclusion our findings suggest that gestational diabetes is associated with elevated levels of ionized magnesium.

Calcium↗

Ionizing radiation synergistic induction of cyclooxygenase-2 with benzo[a]pyrene diol-epoxide through nuclear factor of activated T cells in mouse epidermal Cl 41 cells.

Carcinogenic effects of ionizing radiation and benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), a major metabolite of benzo[a]pyrene (B[a]P), have been well demonstrated both in vitro and in vivo. Two-stage carcinogenesis results indicate that mouse skin is highly susceptible to both ionizing radiation and benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), a major metabolite of benzo[a]pyrene (B[a]P). It is believed that signaling pathways leading to the regulation of gene expression play a significant role in the development of skin cancers. The NFAT family of proteins are important transcription factors involved in the regulation of various target genes, such as IL-1 and TNF-alpha, which play key roles in the regulation of inflammation and carcinogenesis. Thus, the effect of ionizing radiation and B[a]PDE on COX-2 induction and NFAT3 activation, and their relationship, was investigated in mouse epidermal Cl 41 cells. We found that B[a]PDE exposure induced a very high level of NFAT activation in mouse epidermal Cl 41 cells. Ionizing radiation exhibited a synergistic effect with B[a]PDE on NFAT activation and COX-2 induction, while ionizing radiation alone had no effect. By stably knocking down NFAT3 protein expression by means of the specific interfering RNA (siRNA) technique, we found that COX-2 induction by B[a]PDE and the synergistic effect of ionizing radiation with B[a]PDE was totally blocked. These results indicate that ionizing radiation acts synergistically with B[a]PDE on COX-2 induction, and the synergism is dependent on the NFAT3 pathway.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

[Effects of ionization of the air on some bacterial strains].

For some time a bactericidal activity is recognized by air ionization. Recently it has been demonstrated that while the bactericidal effect of the positive ions is due to physical factors, the negative ions operate either by physical or chemical effects. This depends on the presence of oxygen: negative air ionization consists mainly of oxygen ions with a strong oxidizing effect. Beneficial effects of negative air ionization on human health have been recently demonstrated in several studies. In this research the bactericidal effect of the negative air ionization on some strains of Gram+ and Gram- bacteria has been estimated. Trials with Escherichia coli ATCC and Staphylococcus aureus ATCC strains have been carried out using a point-acting tester as generator of negative oxygen ions. The ion concentration was estimated in 8-10(6) ion/cm3 air at a distance from the source of 0.5 metric. The tests were performed in a special room of the microbiology laboratory, equipped without metal furniture and in absence of people. Suspensions of bacterial cells were spread on a solid medium in Petri dishes and then placed, without cover, under the ion generator, at different distances from the source, for 24 hours. The results show a greater effect of the negative air ions on the Gram- than on the Gram+ cells; the number of colonies of Escherichia coli grown under ionization was estimated to be 15.1 times less than of the colonies grown without ionization, while the growth of Staphylococcus aureus in the same conditions was only 4.5. time less. No contamination of Petri dishes by environmental bacteria has ever been occurred during trials: this could demonstrate a biocidal effect of the negative ionization also on air bacteria.

Air↗

Heparin, protamine, and ionized calcium in vitro and in vivo.

The possibility that hypotension associated with protamine or heparin might be related to changes in levels of serum ionized calcium values was determined by in vitro and in vivo studies in dogs. In vitro protamine did not decrease serum calcium levels, but heparin did in a dose-dependent fashion. The reduction ranged from 7% with 10 units/ml of heparin to 20% with 100 units/ml of heparin. Ionized calcium concentrations initially decreased by heparin were restored toward control levels by our increasing the dose of protamine, indicating that the electrostatic attraction between protamine and heparin molecules is stronger than that between heparin and ionized calcium. Despite significant reductions in blood pressure and heart rate, clinical doses of protamine did not decrease ionized calcium in vivo. Although the results of the in vitro study suggested that heparin-induced hypocalcemia might occur in vivo, in vivo heparin caused neither a decrease in ionized calcium nor hypotension. The reduction of ionized calcium by heparin might have been rapidly compensated for in vivo. The results indicate that hypotension due to protamine or heparin is unlikely to be related to changes in serum ionized calcium levels.

Animals↗

Ionized calcium levels in critically ill surgical patients.

Ionized calcium levels measured in 74 critically ill surgical patients averaged 1.97 +/- 0.25 mEq/l, significantly lower than the average (2.26 +/- 0.14) in 34 healthy individuals. The mortality rate increased as ionized calcium levels decreased. Of four patients with ionized calcium levels lower than 1.40 mEq/l, none survived. The average total calcium (4.0u mEq/l) in the critically ill patient was also significantly lower than in controls (4.55 +/- 0.40 mEq/l). The albumin levels were severely reduced (2.80 +/- 0.59 mg/dl) in the patients and significantly lower than in controls (5.31 +/- 0.53 g/dl). There was, however, no correlation between ionized calcium and albumin. Although measured ionized calcium levels correlated with the total calcium level (r = 0.56) and with estimated ionized calcium levels (r = 0.53), it must be emphasized that severe ionic hypocalcemia may occur despite normal total or calculated ionized calcium levels. Consequently, it is hoped that all hospitals with critically ill patients will soon have this analysis available.

Bacterial Infections↗

Effect of Bcl-2 on ionizing radiation and 1-beta-D-arabinofuranosylcytosine-induced internucleosomal DNA fragmentation and cell survival in human myeloid leukemia cells.

1-beta-D-Arabinofuranosylcytosine (ara-C) is an anti-leukemic agent that incorporates into cellular DNA leading to inhibition of DNA synthesis and loss of clonogenic survival. In contrast, ionizing radiation induces DNA damage through the generation of reactive oxygen intermediates. Although little is known of the specific determinants of ara-C and ionizing radiation-induced cytotoxicity, recent work has shown that both are capable of inducing internucleosomal DNA fragmentation in a pattern consistent with programmed cell death (apoptosis). In order to assess the importance of apoptosis in drug and ionizing radiation-induced cytotoxicity in the U-937 myelomonocytic cell line, we created cell lines that constitutively express a transfected bcl-2 gene. Bcl-2 was capable of inhibiting 40-50% of the ara-C and ionizing radiation-induced internucleosomal DNA fragmentation at all tested concentrations. However, cell survival following exposure to these agents was only increased in the bcl-2 transfectants at relatively low doses of ara-C and ionizing radiation. These data demonstrate that although bcl-2 is capable of inhibiting ara-C and ionizing radiation-induced DNA fragmentation in myeloid cells, it increases cell survival only at low doses of these agents. This suggests that apoptosis may be a less important mechanism of cytotoxicity at higher doses of ara-C and ionizing radiation than it is at lower doses.

Cell Survival↗

Serum ionized calcium, parathyroid hormone and phosphate in uremic patients during and between hemodialysis.

The serum concentrations of actual ionized calcium (at actual pH), adjusted ionized calcium (at pH 7.4), pH, intact parathyroid hormone (PTH) and phosphate were studied in ten patients during and between two hemodialysis sessions using a dialysate containing 1.66 mmol/l of calcium. Actual ionized calcium and adjusted ionized calcium increased during hemodialysis from 1.19 to 1.38 and 1.43 mmol/l, respectively (mean values) and returned to predialysis values within five and nine hours postdialysis. Serum PTH decreased from 165 ng/l to 55 ng/l (median values) during hemodialysis but two-hour postdialysis the level did not differ significantly from the predialysis level. Serum phosphate decreased from 2.05 mmol/l to 1.11 mmol/l during hemodialysis, and increased slowly towards the predialysis level. The level of pH increased from 7.40 to 7.47 during hemodialysis and reached predialysis level after nine hours. In a multivariate analysis including actual and adjusted ionized calcium, pH, phosphate and PTH, only actual or adjusted ionized calcium was associated with the level of PTH. We conclude that the effect of dialysate calcium on the levels of ionized calcium and PTH is of very short duration postdialysis.

Adult↗

The significance of ionized calcium in cardiac and critical care. Availability and critical limits at US medical centers and children's hospitals.

The clinical use of ionized calcium has increased since the recognition of its importance in cardiac and critical care medicine. However, more than half the general medical centers in the United States do not provide immediate testing of ionized calcium levels in patients in critical care settings, although indications for this test indicate that they should. The following objectives were used in this study: (1) to determine the availability of ionized calcium testing; (2) to document appropriate critical limits; and (3) to describe the significance of ionized hypocalcemia in cardiac and critical care. The participants were 100 medical centers and 40 children's hospitals in the United States. At medical centers, mean (+/- SD) critical limits were as follows: low, 0.82 +/- 0.14 mmol/L (3.29 +/- 0.56 mg/dL); and high, 1.55 +/- 0.19 mmol/L (6.21 +/- 0.76 mg/dL). At children's hospitals, mean critical limits were as follows: low, 0.85 +/- 0.13 mmol/L (3.41 +/- 0.52 mg/dL); and high, 1.53 +/- 0.11 mmol/L (6.13 +/- 0.44 mg/dL). In the past decade, the availability of ionized calcium testing increased dramatically. Now, 57%, 86%, 95%, and 100% of general hospitals, heart transplant centers, children's hospitals, and pediatric heart transplant centers, respectively, perform testing in house. Collective experience indicates that: (1) aggressive monitoring of ionized calcium prevents cardiac (and neurologic) catastrophes, (2) appropriate levels optimize cardiac function, and (3) calcium repletion is safest when based on acute trends measured directly in whole blood. Hospitals should provide rapid response testing needed during transplantation and massive transfusion and for the diagnosis and treatment of acute ionized hypocalcemia.

Calcium↗

Plasma (total and ionized), erythrocyte and platelet magnesium levels in renal transplant recipients during cyclosporine and/or azathioprine treatment.

We evaluated total and ionized plasma magnesium levels, and erythrocyte and platelet magnesium concentrations from two groups of renal transplant recipients treated either with cyclosporine, azathioprine and prednisolone (group CAP, n = 8) or with azathioprine and prednisolone (group AP, n = 13), and in a group of age- and sex-matched healthy subjects (n = 10). Reduced plasma (total and ionized), erythrocyte and platelet magnesium concentrations were found in both CAP and AP groups with respect to controls (CAP: total plasma Mg median 0.61 vs 0.86 mmol/L, p < 0.01, ionized plasma Mg median 0.43 vs 0.58 mmol/L, p < 0.001, erythrocyte Mg median 2.18 vs 2.56 mmol/L, p < 0.05, platelet Mg median 1.75 vs 2.84 mmol/10(8) cells, p < 0.001; AP: total plasma Mg median 0.62 vs 0.86 mmol/L, p < 0.01, ionized plasma Mg median 0.48 vs 0.58 mmol/L, p < 0.001, erythrocyte Mg median 2.30 vs 2.56 mmol/L, p < 0.05, platelet Mg median 1.75 vs 2.84 mumol/10(8) cells, p < 0.001), while no difference was found between the two groups of transplant recipients as regards plasma and intracellular magnesium levels. Magnesium fractional excretion was higher in transplant recipients than in the control group (Mg fractional excretion median AP 18.6 per cent and CAP 12.8 per cent vs controls 3.5 per cent), whereas no difference was found between patients and control subjects for urinary magnesium 24h excretion. Moreover, in the whole group of transplant recipients (n = 21), urinary magnesium showed an inverse correlation with platelet (rs = -0.54, p < 0.05) and ionized plasma magnesium (rs = -0.48, p < 0.05), and time after transplantation showed a negative correlation with platelet magnesium concentrations (rs = -0.73, p < 0.001), and a direct correlation with fractional magnesium excretion (rs = 0.53, p < 0.05). Finally, a direct relationship between platelet magnesium and ionized plasma magnesium was also detected in the whole group of transplant recipients (rs = 0.47, p < 0.05). Both intraplatelet magnesium depletion and ionized plasma magnesium reduction induced by immunosuppressive therapy could be involved in the increased risk from atherosclerotic disease in renal transplant recipients.

Arteriosclerosis↗

Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex.

Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on apoptosis. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. We investigated the effects of the manganese (III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on ionizing radiation-induced apoptosis. Upon exposure to 2 Gy of gamma-irradiation, there was a distinct difference between the control cells and the cells pre-treated with 5 microM MnTMPyP for 2 h with regard to apoptotic parameters, cellular redox status, mitochondria function, and oxidative damage to cells. MnTMPyP effectively suppressed morphological evidence of apoptosis and DNA fragmentation in U937 cells exposed to ionizing radiation. The [GSSG]/[GSH+GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP(+)+NADPH] ratio was lower in control cells compared to MnTMPyP-treated cells. The ionizing radiation-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of reactive oxygen species, and the reduction of ATP production were significantly higher in control cells compared to MnTMPyP-treated cells. MnTMPyP pre-treated cells showed significant inhibition of apoptotic features such as activation of caspase-3, up-regulation of Bax and p53, and down-regulation of Bcl-2 compared to control cells upon exposure to ionizing radiation. This study indicates that MnTMPyP may play an important role in regulating the apoptosis induced by ionizing radiation presumably through scavenging of reactive oxygen species.

Apoptosis↗

Liquid chromatography/atmospheric pressure ionization mass spectrometry with post-column liquid mixing for the efficient determination of partially oxidized polycyclic aromatic hydrocarbons.

The analytical hyphenation of micro-flow high-performance liquid chromatography (LC), with post-column liquid mixing and mass spectrometric detection (MS) was established to detect partially oxidized polycyclic aromatic hydrocarbons (oxy-PAHs) for low quantity samples. 100pmol injections of 30 reference standards could be detected in good sensitivity using either atmospheric pressure chemical ionization (APCI) and/or atmospheric pressure photoionization (APPI). The connected mass spectrometer was a single quadrupol analyzer realizing simultaneous registration of positive and negative ions in scan range width of 200 - 300Da. The ionization efficiency was compared using three ionization sources (incl. electrospray ionization (ESI)) for several oxy-PAHs. According to the mass spectra, the analytes behave differently in ionization properties. Ionization mechanism (e.g. deprotonated ions and electron captured ions) could be discussed with new inside views. Finally, the hyphenated system was applied to an exemplary aerosol extract and thus highlighting the expedient utilization of this downscaled method for real samples.

Atmospheric Pressure↗

A pulsed triple ionization source for sequential ion/ion reactions in an electrodynamic ion trap.

A pulsed triple ionization source, using a common atmosphere/vacuum interface and ion path, has been developed to generate different types of ions for sequential ion/ion reaction experiments in a linear ion trap-based tandem mass spectrometer. The triple ionization source typically consists of a nano-electrospray emitter for analyte formation and two other emitters, an electrospray emitter and an atmospheric pressure chemical ionization emitter or a second nano-electrospray emitter for formation of the two different reagent ions. The three emitters are positioned in a parallel fashion close to the sampling orifice of the tandem mass spectrometer. The potentials applied to each emitter are sequentially pulsed so that desired ions are generated separately in time and space. Sequential ion/ion reactions take place after analyte ions of interest and different set of reagent ions are sequentially injected into a linear ion trap, where axial trapping is effected by applying an auxiliary radio frequency voltage to the end lenses. The pulsed triple ionization source allows independent optimization of each emitter and can be readily coupled to any atmospheric pressure ionization interface with no need for instrument modifications, provided the potentials required to transmit the ion polarity of interest can be synchronized with the emitter potentials. Several sequential ion/ion reactions examples are demonstrated to illustrate the analytical usefulness of the triple ionization source in the study of gas-phase ion/ion chemistry.

Animals↗

Hypothetical HTLV-I induction by ionizing radiation.

Some laboratories have reported HTLV-I genome integration in cancer patients diagnosed with neoplasms of cervix and uterus. Usually, cancer patients undergo radiotherapy besides chemotherapy and surgery. It is hypothesized that radiation exposure would induce HTLV-I genome generation/activation, nevertheless there is not any report on experimental procedures trying to demonstrate HTLV-I gene expression in cells exposed to ionizing radiation. Anyway, earlier experimental works by Lieberman and Kaplan in 1959 succeeded to isolate retroviral particles, the radiation leukemia virus (RadLV), from thymic lymphomas of X-ray-irradiated C57BL/Ka mice, assuming that RadLV activated in the host by ionizing radiation, is released and transported to the thymus, where lymphoblasts, generated during the postradiation recovery phase, constitute an optimal target cell population for both replication of and eventual transformation by virus. Recent studies claim that besides RadLV, another retrovirus (RadLV-0) also induced by ionizing radiation is expressed and would be responsible for transformed cells of bone marrow origin. Epidemiological studies coincidentally point out to high incidence of HTLV-I infection in geographic areas displaying significant levels of radioactivity contamination as in Central Africa, Japan Islands and Mururoa Atoll. In our research work, we detected HTLV-I antibodies and viral genome integration in cancer patients of cervix and uterus and health care workers, whose had been exposed to ionizing radiation during radiotherapeutic procedures. Recombinational events among endogenous retrovirus and other retrogenic elements in the host cell genome under the bombardment of ionizing radiation from different sources could have optimized the phenomena occurrence or even ignited them to happen, generating HTLV-I genome, related viral peptides and virions. Therefore, it is feasible that exposure to ionizing radiation during therapeutic procedures could generate HTLV-I genome or induce the virus to be expressed in cells of cancer patients submitted to radiotherapy as also in healthy subjects under the same conditions, in artificial or natural radiation environment.

Animals↗

Immobilized artificial membrane chromatography coupled with atmospheric pressure ionization mass spectrometry.

Liquid chromatographic separations on monolayers of cell membrane phospholipids covalently immobilized to silica particles at high molecular density is used for mimicking solute partitioning into biological membranes that generally correlates with membrane transport. This technique called immobilized artificial membrane chromatography usually employs ultraviolet (UV) detection where a single compound is analyzed in a chromatographic run limiting thereby its throughput for drug discovery applications. For coupling with atmospheric pressure ionization mass spectrometry, the phosphate-buffered saline mobile phase was replaced with one that used ammonium acetate as a volatile buffer. While atmospheric pressure chemical ionization accommodated a purely aqueous effluent, interfacing with electrospray ionization required effluent splitting and the addition of an organic modifier (5%, v/v, acetonitrile). Neuropeptide FF antagonists as early-phase drug candidates were used for the comparative evaluation of the methods. Whereas electrospray ionization produced essentially no fragment ions, several compounds involved in our study yielded low-abundance molecular ions with atmospheric pressure chemical ionization. The use of mass spectrometry yielded data that correlated well with those obtained by the method employing UV detection. Both atmospheric pressure ionization methods permitted the simultaneous determination of the k'(IAM), capacity factors and, therefore, an increased-throughput ranking of potential new leads emerged from the drug discovery process based on affinity to artificial membranes.

Atmospheric Pressure↗

Comparison of electrospray, atmospheric pressure chemical ionization, and atmospheric pressure photoionization in the identification of apomorphine, dobutamine, and entacapone phase II metabolites in biological samples.

The applicability of different ionization techniques, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and a novel atmospheric pressure photoionization (APPI), were tested for the identification of the phase II metabolites of apomorphine, dobutamine, and entacapone in rat urine and in vitro incubation mixtures (rat hepatocytes and human liver microsomes). ESI proved to be the most suitable ionization method; it enabled detection of 22 conjugates, whereas APCI and APPI showed only 12 and 14 conjugates, respectively. Methyl conjugates were detected with all ionization methods. Glucuronide conjugates were ionized most efficiently with ESI. Only some of the glucuronides detected with ESI were detected with APCI and APPI. Sulfate conjugates were detected only with ESI. MS/MS experiments showed that the site of glucuronidation or sulfation could not be determined, since the primary cleavage was a loss of the conjugate group (glucuronic acid or SO3), and no site-characteristic product ions were formed. However, it may be possible to determine the site of methylation, since methylated products are more stable than glucuronides or sulfates. Furthermore, the loss of CH3 is not necessarily the primary cleavage, and site characteristic products may be formed. Identification and comparison of conjugates formed from the current model drugs were successfully analyzed in different biological specimens of common interest to biomedical research. A fairly good relation was obtained between the data from in vivo and in vitro models of drug metabolism.

Animals↗

Nanoelectrospray ionization of protein mixtures: solution pH and protein pI.

Solutions consisting of single proteins and mixtures of proteins at different pH values have been subjected to both positive ion and negative ion nanoelectrospray ionization to study the influence of solvent pH and protein pI on the ionization responses of proteins. As has been noted previously, it is possible to form protein ions of one polarity despite the fact that the proteins are present as the opposite polarity in solution. However, total response under this condition tends to be at least an order of magnitude less than the condition in which the nanoelectrospray ionization polarity is the same as the net charge of the proteins in solution. Furthermore, maximum signals in positive ion mode were noted when the pH value of the solution was 4-5 units lower than the protein pI. In the negative ion mode, maximum protein anion signals were observed when the pH was roughly 5 units higher than the protein pI. While only small changes in the abundance-weighted average charge were noted as a function of solution conditions, the extent of sodium ion incorporation was seen to depend strongly on the relationship between net protein charge in solution and gas-phase ion polarity. Sodium ion incorporation was minimized under conditions of maximum signal (i.e., low pH positive ion mode and high pH negative ion mode). Sodium ion incorporation was highest when the protein ion polarities in solution and the gas phase were opposite. These observations are consistent with the charged residue model for electrospray ionization and suggest that a degree of selectivity for electrospray ionization applied to protein mixtures can be realized via judicious selection of solution pH and ionization polarity. Furthermore, the relative extent of sodium ion incorporation under a given set of conditions appears to correlate, at least qualitatively, with protein pI.

Animals↗

Characterizing electrospray ionization using atmospheric pressure ion mobility spectrometry.

Reduced flow rate electrospray ionization has been proven to provide improved sensitivity, less background noise, and improved limits of detections for ESI-MS analysis. Miniaturizing the ESI source from conventional electrospray to microelectrospray and further down to nanoelectrospray has resulted in higher and higher sensitivity; however, when effects of flow rate were investigated for atmospheric pressure ESI-IMS using a nanospray emitter, a striking opposite result was observed. The general tendency we observed in ESI-IMS was that higher flow rate offered higher ion signal intensity throughout a variety of conditions investigated. Thus, further efforts were undertaken to rationalize these contradictory results. It is well accepted that decreased flow rate increases both ionization efficiency and transmission efficiency, thus improving ion signal in ESI-MS. However, our study revealed that decreased flow rate results in decreased ion signal because ion transfer is constant, no matter how flow rate changes in ESI-IMS. Since ion transfer is constant in atmospheric pressure ESI-IMS, ionization efficiency can be studied independently, which otherwise is not possible in ESI-MS in which both ionization efficiency and transmission efficiency vary as conditions alter. In this article, we present a systematic study of signal intensity and ionization efficiency at various experimental conditions using ESI-IMS and demonstrate the ionization efficiency as a function of flow rate, analyte concentration, and solvent composition.

Atmospheric Pressure↗