Electrospray Ionization Technique Research Articles

Validated liquid chromatography–tandem mass spectrometry method for quantitative determination of dauricine in human plasma and its application to pharmacokinetic study

A highly sensitive and selective LC–MS/MS method was developed and validated for the determination of dauricine in human plasma, using protopine as internal standard (IS). The analyte and IS were extracted by liquid–liquid extraction and analyzed by LC–MS/MS. Chromatographic separation was performed on Agilent TC-C 18 column with a mobile phase of methanol–water–glacial acetic acid (60:40:0.8, v/v/v) at a flow rate of 0.7 mL/min. Detection was performed on a triple quadrupole tandem mass spectrum by multiple reaction monitoring (MRM) mode using the electrospray ionization technique in positive mode. The method was linear over the concentration range of 1–200 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL in human plasma with acceptable precision and accuracy. The intra- and inter-day precision was less than 5.9% determined from quality control (QC) samples at concentrations of 2.0, 20.0 and 160 ng/mL, and the accuracy was within ±9.9%. This method was successfully applied for the evaluation of pharmacokinetics of dauricine after oral doses of 100, 300 and 600 mg phenolic alkaloids of menispermum dauricum tablet (PAMDT) to 12 Chinese healthy volunteers.

Validation of a New Liquid Chromatography-Tandem Mass Spectrometry Ion-Trap Technique for the Simultaneous Determination of Thirteen Anticoagulant Rodenticides, Drugs, or Natural Products

The purpose of this study was to develop and validate a liquid chromatography-tandem mass spectrometry method for the identification and quantification of anticoagulant (anti-vitamin K or AVK) compounds, including rodenticides, drugs, and natural products because no published method could be found. The proposed method is based on ion-trap technology with electrospray ionization (ESI) and multiple reaction monitoring (MRM) technique. Each AVK is identified by means of its retention time, precursor ion, and two product ions. Plasma samples are extracted by liquid-liquid partition on Toxi-tube B((R)). The method was validated on dog plasma and gave good results in terms of specificity, linearity, and percent recovery for the 14 AVK tested (warfarin, acenocoumarol, bromadiolone, brodifacoum, chlorophacinone, coumatetralyl, dicoumarol, difenacoum, difethialone, flocoumafen, fluindione, phenindione, and tioclomarol). The limits of detection ranged from 5 to 25 ng/mL. Intraday repeatability was good, but interday repeatability was more variable though still sufficient for our diagnostic purposes. The technique was successfully applied in a series of clinical investigations to demonstrate its applicability in various animal species and gave very high sensitivity and specificity results.

Simultaneous determination of etoposide and a piperine analogue (PA-1) by UPLC–qTOF-MS: Evidence that PA-1 enhances the oral bioavailability of etoposide in mice

In the present investigation, a UPLC–qTOF-MS/MS method has been developed for the simultaneous determination of etoposide and a piperine analogue, namely, 4-ethyl 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1). The analytes were separated on a reverse phase C18 column using methanol–water (72:28, v/v) mobile phase with a flow rate of 250 μL/min. The qTOF-MS was operated under multiple reaction monitoring mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions for etoposide and PA-1 were at m/ z 185.1350 and 164.1581, respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique. The total run time was 6 min and the elution of etoposide and PA-1 occurred at 1.24 and 2.84 min, respectively. The calibration curves of etoposide as well as PA-1 were linear over the concentration range of 2–1000 ng/mL ( r 2, 0.9829), and 1–1000 ng/mL ( r 2, 0.9989), respectively. For etoposide intra-assay and inter-assay accuracy in terms of % bias was in between −7.65 to +6.26, and −7.83 to +5.99, respectively. For PA-1 intra-assay and inter-assay accuracy in terms of % bias was in between −7.01 to +9.10, and −7.36 to +6.71, respectively. The lower limit of quantitation for etoposide and PA-1 were 2.0 and 1.0 ng/mL, respectively. Analytes were stable under various conditions (in autosampler, during freeze–thaw, at room temperature, and under deep-freeze conditions). The method was used for a pharmacokinetic study which showed that PA-1 enhanced the oral bioavailability of etoposide in mice by 2.32-fold.

Comparison of Electron Capture—Atmospheric Pressure Chemical Ionization and Electrospray Ionization for the Analysis of Gambogic Acid and its Main Circulating Metabolite in Dog Plasma

Gambogic acid (GA), a promising anticancer candidate, is a polyprenylated xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi. Electron capture-atmospheric pressure chemical ionization (EC- APCI) and electrospray ionization (ESI) techniques, both in the negative ion mode, were evaluated regarding ionization, fragmentation patterns and sensitivity for simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of GA and its main circulating metabolite, 10-hydroxygambogic acid (10-OHGA) in dog plasma. Both analytes underwent extensive in-source fragmentation in EC-APCI, which was not desirable for reliable quantification of these analytes, whereas the substitution of ESI for EC-APCI almost eliminated the source instability of both analytes. Negative ion ESI was, therefore, chosen for the development of an LC-MS/MS method for simultaneous determination of these analytes. After protein precipitation by acetonitrile, all analytes were separated on a Luna C18 HST column (50 x 2.0 mm i.d., 2.5 microm) with a mobile phase of 20 mmol L(-1) ammonium acetate water solution containing 0.2% acetic acid:acetonitrile (18:82, v/v). The detection was performed on a tandem mass spectrometer using selective reaction monitoring mode. Calibration curves were linear over the range of 10-6000 ng mL(-1) for GA and 3-2000 ng mL(-1) for 10-OHGA. The method was successfully applied to the pharmacokinetics study of GA injection in six beagle dogs.

Determination of Fesoterodine in Pharmaceutical Formulations by Using Liquid Chromatography—Tandem Mass Spectrometry

A simple, fast, sensitive, and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of fesoterodine (FESO) in pharmaceutical formulations was developed and validated using manidipine as internal standard (IS). The LC-MS/MS method was carried out on a Luna C8(2) column (50 mm × 3.0 mm i.d., µm) with a mobile-phase consisting of methanol/0.1% formic acid (90:10, v/v). The mass spectrometry method was performed employing a positive electrospray ionization technique, operating in multiple reaction monitoring mode (MRM), monitoring the transitions of 412.2→223.0 and 611.1→167.0 for FESO and IS, respectively. The total analysis time was 2 min and it was linear in the concentration range of 5-1000 ng mL(-1). Placebo solution and mobile-phase components were evaluated on the specificity test and did not interfere with the analyte or the IS. Intra-day and inter- day precision and accuracy evaluated by RSDs and relative errors, respectively, were lower than 5% for all analytes. The method proved to be robust by a fractional factorial design evaluation. The proposed method was successfully applied for the quantitative analysis of FESO in tablet formulations to support the quality control.

Electrospray-Assisted Ultraviolet Aerodynamic Particle Sizer Spectrometer for Real-time Characterization of Bacterial Particles

The ultraviolet aerodynamic particle sizer (UVAPS) spectrometer is a novel, commercially available aerosol counter for real-time, continuous monitoring of viable bioaerosols based on the fluorescence induced from living microorganisms. For aerosolization of liquid-based microorganisms, general aerosolization methods such as atomization or nebulization may not be adequate for an accurate and quantitative characterization of the microorganisms because of the formation of agglomerated particles. In such cases, biological electrospray techniques have an advantage because they generate nonagglomerated particles, attributable to the repulsive electrical forces among particles with unipolar charges. Biological electrosprays are quickly gaining potential for the detection and control of living organisms in applications ranging from mass spectrometry to developmental microbiology. In this study, we investigated the size distribution, total concentration, and fluorescence percentage of bacterial particles in a real-time manner by electrospray-assisted UVAPS. A suspension containing Escherichia coli as a test microorganism was sprayed in a steady cone-jet mode using a specially designed electrospray system with a point-to-orifice-plate configuration based on charge-reduced electrospray size spectrometry. With the electrospray process, 98% of the total E. coli particle number concentration had a size of <1 mum and the geometric mean diameter was 0.779 mum, as compared with the respective values of 78% and 0.907 mum after nebulization. The fractions of fluorescence responsive particles and of particles that contained viable organisms in culture were 12% and 7%, respectively, from the electrospray process and 34% and 24% from nebulization. These results demonstrate that (1) the presence of agglomerated particles can lead to markedly overestimated fluorescence and culturability percentages compared with the values obtained from nonagglomerated particles, and (2) electrospray-assisted UVAPS can provide more accurate and quantitative real-time characterization of liquid-based microorganisms, owing to the generation of nonagglomerated particles.

Liquid chromatographic–tandem mass spectrometry assay for quantitation of a novel antidiabetic S002‐853 in rat plasma and its application to pharmacokinetic study

A sensitive and selective LC-MS/MS method has been developed and validated for the estimation of novel antidiabetic synthetic flavonoid S002-853 in rat plasma using centchroman as an internal standard. The method involves a simple two-step liquid-liquid extraction with diethyl ether. The analyte was chromatographed on a Pierce Spheri-5, guard cyano column (30 x 4.6 mm i.d., 5 microm) with isocratic mobile phase consisting of methanol-ammonium acetate buffer (pH 4.6, 10 mm; 90 : 10, v/v) at a flow rate of 0.75 mL/min. The API 4000 triple-quadrupole LC-MS/MS system was operated under multiple reaction-monitoring mode. The ionization was performed by electrospray ionization technique in positive ion mode. The chromatographic run time was 6 min and the weighted (1/x(2)) calibration curves were linear over the range 0.78-400 ng/mL. The limit of detection and lower limit of quantification were 0.195 and 0.78 ng/mL, respectively. The intra- and inter-batch accuracy (%bias) and precision (%RSD) were found to be less than 8.47 and 11.6% respectively. The average absolute recoveries of S002-853 and internal standard from spiked plasma samples were >90%. S002-853 was stable for 8 h at ambient temperature, 4 weeks at -60 degrees C and after three freeze-thaw cycles. The assay was successfully applied to determine the pharmacokinetic parameters in male Sprague-Dawley rats after an oral dose administration at 25 mg/kg.

Liquid chromatograph/tandem mass spectrometry assay for the simultaneous determination of chlorogenic acid and cinnamic acid in plasma and its application to a pharmacokinetic study

A rapid and high sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for simultaneous determination of chlorogenic acid and cinnamic acid in human plasma was developed. The analytes and internal standard (IS), tinidazole, were extracted from human plasma via liquid/liquid extraction with ether–ethyl acetate (1:1, v/v) and separated on an Agilent Zorbax SB C18 column within 5 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring (MRM) and negative ion mode. The precursor to product ion transitions monitored for chlorogenic acid, cinnamic acid and IS were m/ z 352.9 → 191.1, 146.8 → 103.1, 245.6 → 126.0, respectively. The assay was validated with linear range of 1.00–800.00 ng/mL for chlorogenic acid and 0.50–400.00 ng/mL for cinnamic acid. The intra- and inter-day precisions (RSD%) were within 9.05% for each analyte. The absolution recoveries were greater than 74.62% for chlorogenic acid and 76.21% for cinnamic acid. Each analyte was proved to be stable during all sample storage, preparation and analytic procedures. The method was successfully applied to a pharmacokinetic study of Mailuoning injection in 10 healthy volunteers.

LC–MS/MS method for the simultaneous determination of ethyl gallate and its major metabolite in rat plasma

A simple, rapid and sensitive liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed and validated for the determination of ethyl gallate, a pharmacologically active constituent isolated from Lagerstroemia speciosa (Linn.) Pers. This method was used to examine the pharmacokinetics of ethyl gallate and its major metabolite gallic acid in rat plasma using propyl gallate as an internal standard. After precipitation of the plasma proteins with acetonitrile, the analytes were separated on a Zorbax SB-C(18) column (3.5 microm, 2.1 x 50 mm) with an isocratic mobile phase consisted of methanol-acetonitrile-10 mM ammonium acetate (10 : 25 : 65, v/v/v) containing 0.1% formic acid at a flow rate of 0.25 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple-reaction monitoring mode using the electrospray ionization technique in negative mode. The lower limits of quantification of gallic acid and ethyl gallate of the method were 0.5 and 1.0 ng/mL. The intra-day and inter-day accuracy and precision of the assay were less than 8.0%. This method has been applied successfully to a pharmacokinetic study involving the intragastric administration of ethyl gallate to rats.

A Corona Discharge Initiated Electrochemical Electrospray Ionization Technique

We report here the development of a corona discharge (CD) initiated electrochemical (EC) electrospray ionization (ESI) technique using a standard electrospray ion source. This is a new ionization technique distinct from ESI, electrochemistry inherent to ESI, APCI, and techniques using hydroxyl radicals produced under atmospheric pressure conditions. By maximizing the observable CD at the tip of a stainless steel ESI capillary, efficient electrochemical oxidation of electrochemically active compounds is observed. For electrochemical oxidation to be observed, the ionization potential of the analyte must be lower than Fe. Ferrocene labeled compounds were chosen as the electrochemically active moiety. The electrochemical cell in the ESI source was robust, and generated ions with selectivity according to the ionization potential of the analytes and up to zeptomolar sensitivity. Our results indicate that CD initiated electrochemical ionization has the potential to become a powerful technique to increase the dynamic range, sensitivity, and selectivity of ESI experiments.

Quadrupole ion traps

The extraordinary story of the three-dimensional radiofrequency quadrupole ion trap, accompanied by a seemingly unintelligible theoretical treatment, is told in some detail because of the quite considerable degree of commercial success that quadrupole technology has achieved. The quadrupole ion trap, often used in conjunction with a quadrupole mass filter, remained a laboratory curiosity until 1979 when, at the American Society for Mass Spectrometry Conference in Seattle, George Stafford, Jr., of Finnigan Corp., learned of the Masters' study of Allison Armitage of a combined quadrupole ion trap/quadrupole mass filter instrument for the observation of electron impact and chemical ionization mass spectra of simple compounds eluting from a gas chromatograph. Stafford developed subsequently the mass-selective axial instability method for obtaining mass spectra from the quadrupole ion trap alone and, in 1983, Finnigan Corp. announced the first commercial quadrupole ion trap instrument as a detector for a gas chromatograph. In 1987, confinement of ions generated externally to the ion trap was demonstrated and, soon after, the new technique of electrospray ionization was shown to be compatible with the ion trap.

Determination of Olanzapine in Whole Blood Using Simple Protein Precipitation and Liquid Chromatography-Tandem Mass Spectrometry

A simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of the antipsychotic drug olanzapine in whole blood using dibenzepine as internal standard (IS). After acidic methanol-induced protein precipitation of the whole blood samples, olanzapine and IS were chromatographed on a reversed-phase Zorbax Extend-C(18)-column at pH 9.0. Quantification was performed on a triple-quadrupole mass spectrometer employing electrospray ionization technique operating in multiple reaction monitoring and positive ion mode. Total chromatographic run time was 15 min, and calibration curve was linear over the concentration range of 0.005 to 0.50 mg/kg olanzapine in whole blood. The method was validated for selectivity, matrix interference, recovery, linearity, limit of detection, limit of quantitation (LOQ), accuracy, precision, and stability. The absolute recovery obtained was 103% for olanzapine and 68% for IS. An LOQ of 0.005 mg/kg olanzapine in whole blood was achieved. Inter- and intraday precision were less than 11% within concentrations from 0.01 to 0.50 mg/kg, and the accuracy ranged from 85 to 115%. The method was subsequently applied to 27 authentic samples, of which 20 were postmortem blood samples, from forensic investigations.

Determination of fenofibric acid in human plasma by ultra performance liquid chromatography–electrospray ionization mass spectrometry: application to a bioequivalence study

A rapid, specific and sensitive ultra-performance liquid chromatography tandem mass spectrometry method was developed for the determination of fenofibric acid in human plasma. The method involves simple, one-step liquid-liquid extraction procedure coupled with an Acquity UPLC(TM) BEH C(18) column (50 x 2.1 mm, i.d., 1.7 microm) with isocratic elution at a flow-rate of 0.2 mL/min and mefenamic acid was used as the internal standard. The Quattro Premier XE mass spectrometry was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. Using 250 microL plasma, the methods were validated over the concentration rang 0.05-7.129 microg/mL, with a lower limit of quantification of 0.05 microg/mL. The intra- and inter-day precision and accuracy were within 9.3%. The recovery was 66.7% and 52.6% for fenofibric acid, and mefenamic acid, respectively. Total run time was 1.8 min only for each sample, which makes it possible to analyze more than 350 samples per day.

Development of a novel HPLC‐MS/MS method for the determination of aconitine and its application to in vitro and rat microdialysis samples

A sensitive and selective LC-MS/MS method was developed and validated for the determination of aconitine in microdialysate and rat plasma. Extraction of plasma sample was conducted by use of 1% trichloracetic acid and acetonitrile solution with 10 ng/mL internal standard (propafenone) spiked. Microdialysates were analyzed without sample purification. After sample preparation, 2 microL were injected and separated with an isocratic mobile phase consisting of acetonitrile:0.1% formic acid (60:40, v/v) at a flow rate of 0.3 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple-reaction monitoring mode (MRM) using the electrospray ionization technique in positive mode. Overall, the assay exhibited good precision and accuracy. The diffusion properties of aconitine investigated in in vitro microdialysis experiments revealed unfavourable concentration dependence avertable by keeping a constant pH 5.77 using isotonic phosphate buffer solution as perfusate. The mean relative recoveries were 48.23% [coefficient of variation (CV 4.47%)] and 55.38% (CV 2.89%) for retrodialysis and recovery experiments, respectively. The in vivo recovery of aconitine was 34.48% (CV 3.05%) and was stable over the 6 h study period. Following characterization of aconitine both in vitro and in vivo microdialysis, the developed setting is suitable for application in pharmacokinetics and pharmacodynamics studies.

LC–MS–MS Development and Validation for Simultaneous Quantitation of Metformin, Glimepiride and Pioglitazone in Human Plasma and Its Application to a Bioequivalence Study

A simple, precise and reproducible liquid chromatography–tandem mass spectrometry method has been developed and validated according to the Food and Drug Administration guidelines for the simultaneous quantitation of antidiabetic drugs metformin, glimiperide and pioglitazone in human plasma using glipizide as an internal standard. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring and positive ion mode. Inter-batch and intra-batch coefficient of variation across four validation runs for the quality control samples was less than 7%. The accuracy determined at quality control levels was within 92.81–105.13%. The method was applied to a bioequivalence study.

Generation of Nonagglomerated Airborne Bacteriophage Particles Using an Electrospray Technique

Biological electrospray techniques are rapidly becoming a promising means for controlling living organisms in applications ranging from mass spectrometry to developmental biology. We investigated the generation characteristics of airborne MS2 bacteriophage particles <30 nm in size, using an electrospray technique. A suspension containing bacteriophage MS2 was sprayed in cone-jet mode using a specially designed electrospray system with a point-to-orifice-plate configuration mentioned in previous studies based on a charge reduced electrospray size spectrometry. The highly charged droplets were discharged rapidly into a radioactive neutralizer of Po(210). The electrosprayed airborne MS2 particles (23.8 +/- 0.49 nm GMD) maintained their monodisperse size distribution with good stability and uniformity for >1 h. Compared with the generation characteristics observed using the previous nebulization process (51.5 +/- 0.86 nm GMD), this electrospray technique produced nonagglomerated particles, resulting in a narrow size range of generated particles. The total MS2 particle number concentration and GMD increased with changes in the suspension flow rate from 5 to 25 microL/h. As the applied voltage increased in cone-jet mode, the GMD and culturable bacteriophage concentration decreased slightly. Our investigation shows that the electrospray process, driven by high-intensity electric fields, can be used for nanometer-sized living organisms.

MALDI, AP/MALDI and ESI techniques for the MS detection of amyloid β-peptides

Amyloid β-peptides (Aβs) are involved in several neuropathological conditions such as Alzheimer's disease and considerable experimental evidences have emerged indicating that different proteases play a major role in regulating the accumulation of Aβs in the brain. Particularly, insulin-degrading enzyme (IDE) has been shown to degrade Aβs at different cleavage sites, but the experimental results reported in the literature and obtained by mass spectrometry methods are somehow fragmentary. The detection of Aβs is often complicated by solubility issues, oxidation artifacts and spontaneous aggregation/cleavage and, in order to rationalize the different reported results, we analyzed Aβs solutions by three different MS approaches: matrix assisted laser desorption ionization-time of flight (MALDI-TOF), atmospheric pressure (AP) MALDI ion trap and electrospray ionization (ESI) ion trap. Differences in the obtained results are discussed and ESI is chosen as the most suitable MS method for Aβs detection. Finally, cleavage sites produced by interaction of Aβs with IDE are identified, two of which had never been reported in the literature.

A liquid chromatography‐tandem mass spectrometry method for the simultaneous determination of exemestane and its metabolite 17‐dihydroexemestane in human plasma

A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitation of exemestane (Exe) and its main metabolite 17-dihydroexemestane (DhExe) in human plasma. The analytes were extracted by protein precipitation with acetonitrile, containing stable 13C-labelled Exe (13C3-Exe) as internal standard, and measured by LC-MS/MS. The best chromatographic separation of the analytes from the interferences was achieved by using a Phenyl column operating under isocratic regime conditions. The total chromatographic runtime was 5.0 min and the elution of Exe and DhExe occurred at 2.5 min and 2.9 min, respectively. Quantitation was performed by employing the positive electrospray ionization (ESI) technique and multiple reaction monitoring mode (MRM). The monitored precursor to product-ion transitions for Exe, DhExe and 13C3-Exe internal standard were m/z 297.0 --> 120.8, m/z 299.1 --> 134.9 and m/z 300.0 --> 123.2, respectively. The lower limit of quantitation (LLOQ) was 0.1 ng/ml for DhExe and 0.2 ng/ml for Exe. The method was linear up to 36-51 ng/ml with r2 > or = 0.998. The intra- and inter-assay precision were < or = 7.7% and 5.1% for Exe and < or = 8.1 and 4.9% for DhExe while deviations from nominal values were in the 1.5-13.2% and - 9.0-5.8% ranges for Exe and DhExe, respectively. The analytical method resulted robust and suitable for pharmacokinetic monitoring of Exe and its main metabolite during adjuvant therapy in patients with breast cancer.

Development and validation of a high throughput and robust LC–MS/MS with electrospray ionization method for simultaneous quantitation of diltiazem and its two metabolites in human plasma: Application to a bioequivalence study

A high throughput and specific method using ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) was developed for the simultaneous determination of diltiazem and its two metabolite (N-desmethyldiltiazem and O-desacetyldiltiazem) in human plasma. A one-step liquid–liquid extraction (LLE) with methyl- t-butyl ether (MTBE) involved for the extraction of diltiazem (DLTZ), metabolites (DMeD and DAcD) and internal standard. Analytes were chromatographed on a ACQUITY UPLC™ BEH C 18 column (100 mm × 2.1 mm, i.d., 1.7 μm) with isocratic elution at a flow rate of 0.2 mL/min using 10 mM ammonium acetate buffer–acetonitrile (25:75, v/v). The Quattro Premier XE LC–MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique. Using 300 μL plasma, the method was validated over the concentration range 0.48–639.9 ng/mL for DLTZ and 0.24–320.1 for DMeD and 0.24–320.7 ng/mL for DAcD, with a lower limit of quantification of 0.48 ng/mL for DLTZ and 0.24 ng/mL for metabolites. The intra- and inter-day precision and accuracy were within 10.0%. The recovery was 77.4%, 76.0%, 74.5% and 74.1% for DLTZ, DMeD, DAcD and Ziprasidone, respectively. Total run time was 2.0 min only.

Applications of Electrostatic Spray Techniques to Surface Cleaning

Conventional cleaning technologies have been effective in removal of particles, metals, and organic films. However, two trends motivating the development of new techniques are 1) the desire to minimize the environmental impact of large volumes of cleaning solutions; and 2) the need to clean at the sub-45 nm level, consistent with decreasing feature sizes. We report here on the initial characterization of a system to apply electrospray techniques to variants of the SC-1 and SC-2 solutions, as well as to solvent mixtures. We describe the generation of submicron sized droplets (&lt;1 m radius) of cleaning mixtures and demonstrate a preliminary methodology, using a combination of experimental data and phenomenological modeling approaches, to characterize the physics of the droplet-surface interaction