Polarization induced electrospray ionization mass spectrometry for the analysis of liquid,viscous and solid samples

In this study, a polarization‐induced electrospray ionization mass spectrometry (ESI‐MS) was developed. A micro‐sized sample droplet was deposited on a naturally available dielectric substrate such as a fruit or a stone, and then placed close to (~2 mm) the orifice of a mass spectrometer applied with a high voltage. Taylor cone was observed from the sample droplet, and a spray emitted from the cone apex was generated. The analyte ion signals derived from the droplet were obtained by the mass spectrometer. The ionization process is similar to that in ESI although no direct electric contact was applied on the sample site. The sample droplet polarized by the high electric field provided by the mass spectrometer initiated the ionization process. The dielectric sample loading substrate facilitated further the polarization process, resulting in the formation of Taylor cone. The mass spectral profiles obtained via this approach resembled those obtained using ESI‐MS. Multiply charged ions dominated the mass spectra of peptides and proteins, whereas singly charged ions dominated the mass spectra of small molecules such as amino acids and small organic molecules. In addition to liquid samples, this approach can be used for the analysis of solid and viscous samples. A small droplet containing suitable solvent (5–10 µl) was directly deposited on the surface of the solid (or viscous) sample, placed close the orifice of mass spectrometer applied with a high voltage. Taylor cone derived from the droplet was immediately formed followed by electrospray processes to generate gas‐phase ions for MS analysis. Analyte ions derived from the main ingredients of pharmaceutical tablets and viscous ointment can be extracted into the solvent droplet in situ and observed using a mass spectrometer. Copyright © 2015 John Wiley & Sons, Ltd.     

Real time monitoring of accelerated chemical reactions by ultrasonication‐assisted spray ionization mass spectrometry

Ultrasonication has been used to accelerate chemical reactions. It would be ideal if ultrasonication‐assisted chemical reactions could be monitored by suitable detection tools such as mass spectrometry in real time. It would be helpful to clarify reaction intermediates/products and to have a better understanding of reaction mechanism. In this work, we developed a system for ultrasonication‐assisted spray ionization mass spectrometry (UASI–MS) with an ~1.7 MHz ultrasonic transducer to monitor chemical reactions in real time. We demonstrated that simply depositing a sample solution on the MHz‐based ultrasonic transducer, which was placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Singly and multiply charged ions from small and large molecules, respectively, can be observed in the UASI mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup accelerates the chemical reactions while being monitored via UASI–MS. The feasibility of using this approach for real‐time acceleration/monitoring of chemical reactions was demonstrated. The reactions of Girard T reagent and hydroxylamine with steroids were used as the model reactions. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions are readily generated and instantaneously monitored using MS within 1 s. Additionally, we also showed the possibility of using this reactive UASI–MS approach to assist the confirmation of trace steroids from complex urine samples by monitoring the generation of the product ions. Copyright © 2014 John Wiley & Sons, Ltd.     

On-line monitoring of Brookhart polymerization by electrospray ionization mass spectrometry

For the first time, an electrospray ionization (ESI) mass spectrometer coupled on-line with a microreactor permitted the fast screening of polymerization growth of alkenes in the liquid phase mediated by palladium Brookhart catalyst and allowed the direct mass spectrometric identification of alkyl chains still bonded to Pd. The method also allowed us to intercept the catalytically active cationic intermediates of the Brookhart polymerization of alkenes, and to prove on-line their catalytic activity through ion/molecule reactions. The technique is fast and sensitive, requires no sample preparation and manipulation, and is therefore suitable for the fast screening of catalyst/polymer growth by MS identification, with potential applications in areas such as new catalyst development, polymer chemistry, and product quality monitoring in manufacturing.     

Direct analysis of anabolic steroids in urine using Leidenfrost phenomenon assisted thermal desorption-dielectric barrier discharge ionization mass spectrometry

Rapid detection of trace level anabolic steroids in urine is highly desirable to monitor the consumption of performance enhancing anabolic steroids by athletes. The present article describes a novel strategy for identifying the trace anabolic steroids in urine using Leidenfrost phenomenon assisted thermal desorption (LPTD) coupled to dielectric barrier discharge (DBD) ionization mass spectrometry. Using this method the steroid molecules are enriched within a liquid droplet during the thermal desorption process and desorbed all-together at the last moment of droplet evaporation in a short time domain. The desorbed molecules were ionized using a dielectric barrier discharge ion-source in front of the mass spectrometer inlet at open atmosphere. This process facilitates the sensitivity enhancement with several orders of magnitude compared to the thermal desorption at a lower temperature. The limits of detection (LODs) of various steroid molecules were found to be in the range of 0.05–0.1 ng mL⁻¹ for standard solutions and around two orders of magnitude higher for synthetic urine samples. The detection limits of urinary anabolic steroids could be lowered by using a simple and rapid dichloromethane extraction technique. The analytical figures of merit of this technique were evaluated at open atmosphere using suitable internal standards. The technique is simple and rapid for high sensitivity and high throughput screening of anabolic steroids in urine.     

Rapid bioanalysis of vancomycin in serum and urine by high-performance liquid chromatography tandem mass spectrometry using on-line sample extraction and parallel analytical columns

A novel high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS) method is described for the determination of vancomycin in serum and urine. After the addition of internal standard (teicoplanin), serum and urine samples were directly injected onto an HPLC system consisting of an extraction column and dual analytical columns. The columns are plumbed through two switching valves. A six-port valve directs extraction column effluent either to waste or to an analytical column. A ten-port valve simultaneously permits equilibration of one analytical column while the other is used for sample analysis. Thus, off-line analytical column equilibration time does not require mass spectrometer time, freeing the detector for increased sample throughput. The on-line sample extraction step takes 15 seconds followed by gradient chromatography taking another 90 seconds. Having minimal sample pretreatment the method is both simple and fast. This system has been used to successfully develop a validated positive-ion electrospray bioanalytical method for the quantitation of vancomycin. Detection of vancomycin was accurate and precise, with a limit of detection of 1 ng/mL in serum and urine. The calibration curves for vancomycin in rat, dog and primate were linear in a concentration range of 0.001-10 microg/mL for serum and urine. This method has been successfully applied to determine the concentration of vancomycin in rat, dog and primate serum and urine samples from pharmacokinetic and urinary excretion studies.     

Infrared Laser Ablation Sample Transfer for MALDI and Electrospray

We have used an infrared laser to ablate materials under ambient conditions that were captured in solvent droplets. The droplets were either deposited on a MALDI target for off-line analysis by MALDI time-of-flight mass spectrometry or flow-injected into a nanoelectrospray source of an ion trap mass spectrometer. An infrared optical parametric oscillator (OPO) laser system at 2.94 μm wavelength and approximately 1 mJ pulse energy was focused onto samples for ablation at atmospheric pressure. The ablated material was captured in a solvent droplet 1–2 mm in diameter that was suspended from a silica capillary a few millimeters above the sample target. Once the sample was transferred to the droplet by ablation, the droplet was deposited on a MALDI target. A saturated matrix solution was added to the deposited sample, or in some cases, the suspended capture droplet contained the matrix. Peptide and protein standards were used to assess the effects of the number of IR laser ablation shots, sample to droplet distance, capture droplet size, droplet solvent, and laser pulse energy. Droplet collected samples were also injected into a nanoelectrospray source of an ion trap mass spectrometer with a 500 nL injection loop. It is estimated that pmol quantities of material were transferred to the droplet with an efficiency of approximately 1%. The direct analysis of biological fluids for off-line MALDI and electrospray was demonstrated with blood, milk, and egg. The implications of this IR ablation sample transfer approach for ambient imaging are discussed.     

Direct quantification of creatinine in human urine by using isotope dilution extractive electrospray ionization tandem mass spectrometry

Urinary creatinine (CRE) is an important biomarker of renal function. Fast and accurate quantification of CRE in human urine is required by clinical research. By using isotope dilution extractive electrospray ionization tandem mass spectrometry (EESI–MS/MS) a high throughput method for direct and accurate quantification of urinary CRE was developed in this study. Under optimized conditions, the method detection limit was lower than 50 μg L⁻¹. Over the concentration range investigated (0.05–10 mg L⁻¹), the calibration curve was obtained with satisfactory linearity (R² = 0.9861), and the relative standard deviation (RSD) values for CRE and isotope-labeled CRE (CRE-d3) were 7.1–11.8% (n = 6) and 4.1–11.3% (n = 6), respectively. The isotope dilution EESI–MS/MS method was validated by analyzing six human urine samples, and the results were comparable with the conventional spectrophotometric method (based on the Jaffe reaction). Recoveries for individual urine samples were 85–111% and less than 0.3 min was taken for each measurement, indicating that the present isotope dilution EESI–MS/MS method is a promising strategy for the fast and accurate quantification of urinary CRE in clinical laboratories.     

High‐throughput polymer tip‐electrospray ionization mass spectrometry for enhanced detection of neopterin and biopterin in clinical urine samples

Urinary biopterin (Bio) and neopterin (Neo) are important markers for clinical diagnosis of hyperphenylalaninemia. Herein, we developed a high‐throughput analysis method based on electrospray ionization mass spectrometry (ESI‐MS) with polymer tips for the rapid quantitative detection of Bio and Neo in clinical urine samples. Different polymer tips were investigated. It is found that the best detection sensitivity was achieved with hydrophobic polymer tip, ie, polyethylene tips. The high‐throughput polymer tip‐ESI‐MS method allowed a rapid analysis speed at ~40 seconds per sample. The limits of quantification (LOQ) (S/N ≥ 10) for the detection of Bio and Neo were improved to be 5.0 ng/mL. Acceptable relative standard deviation (RSD) values for Neo and Bio were measured to be 12.2% and 13.4% for direct measurement of Bio and Neo in raw urine samples, respectively. Furthermore, Bio and Neo were directly quantified from 18 clinical urine samples by presented method. The ratios of urinary Bio‐to‐Neo were analyzed for diagnosis of hyperphenylalaninemia. The results demonstrated that the present polymer tip‐ESI‐MS method is a promising strategy for the rapid analysis of clinical samples.     

Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing.     

Screening for anabolic steroids in doping analysis by liquid chromatography/electrospray ion trap mass spectrometry

A fast and selective LC/MS/MS method for the screening of four anabolic steroids in human urine has been developed and validated. Liquid-liquid extraction with diethyl ether was applied after enzymatic hydrolysis. Analyses were performed on an ion trap mass spectrometer equipped with electrospray ionisation. MS/MS was applied for all compounds. The analytical run time was 11 min. The LOD for all compounds varied between 1 and 10 ng/mL. Left-over A samples, which were declared positive by GC/MS for the presence of 3'-hydroxystanozolol, were assessed using the described method.     

Developing LC–MS/MS methods to quantify rivaroxabanin human plasma and urine: Application to therapeutic drug monitoring

Rivaroxaban is an oral anticoagulant directly inhibiting the activity of Factor Xa, which is widely used for the prophylaxis of thromboembolic disorders. Therapeutic drug monitoring (TDM) is required during therapy for individual dosage adjustment. This study aimed at developing a liquid chromatography/tandem mass spectrometry method that was suitable for rivaroxaban TDM in human plasma and urine and exploring the feasibility of urine drug monitoring in medical care. A 3 min run time of the LC–MS/MS methods was established by employing an Acquity UPLC BEH C₁₈ (2.1 × 50 mm, 1.7 μm) column using gradient elution of 10 mmol/L ammonium acetate containing 0.1% formic acid–0.1% formic acid acetonitrile as a mobile phase at a flow rate of 0.4 ml/min with calibration ranges of 0.5–400 and 10–10,000 ng/ml for human plasma and urine, respectively. Rivaroxaban was detected on a triple quadrupole tandem mass spectrometer with an electrospray ionization source in positive ion mode. The methods showed good linearity within the calibration range. The precision and accuracy, matrix effect, extraction recovery and stability in both human matrices were all validated and meet the international guideline requirements. These validated methods were successfully applied to support the TDM of an aged patient receiving rivaroxaban for therapy.     

Daptomycin determination by liquid chromatography–mass spectrometry in peritoneal fluid, blood plasma, and urine of clinical patients receiving peritoneal dialysis treatment

A 13-min LC–MS method was developed for the determination of daptomycin, a new potent antibiotic, in peritoneal fluid, blood plasma, and urine of patients receiving renal replacement therapy. Chromatography was performed on a C₁₈ column and detection was performed by a single-quadrupole mass spectrometer coupled to LC via an electrospray interface (ESI). The column effluent was also monitored at 370 nm using a photodiode-array detector. The developed method provided a linear dynamic range for concentrations from 0.5 μg mL⁻¹ to 100 μg mL⁻¹. Method precision and accuracy were found to be satisfactory for clinical application, thus the method was successfully used for the analysis of daptomycin in pharmacokinetic studies. The drug was preventively administered against Gram-positive infections to 19 clinical patients undergoing peritoneal dialysis. Peritoneal fluid, blood plasma, and urine samples were collected at 13 time points over a period of 48 h. Clinical samples were analysed following simple sample-preparation procedures and daptomycin was unambiguously detected and quantified.     

Sensitive quantification of clozapine and its main metabolites norclozapine and clozapine-<Emphasis Type="Italic">N</Emphasis>-oxide in serum and urine using LC-MS/MS after simple liquid–liquid extraction work-up

An LC-MS/MS method for the determination of the atypic neuroleptic clozapine and its two main metabolites norclozapine and clozapine-N-oxide has been developed and validated for serum and urine. After addition of d4-clozapine as deuterated internal standard a fast single-step liquid–liquid extraction under alkaline conditions and with ethyl acetate as organic solvent followed. The analytes were chromatographically separated on a Synergi Polar RP column using gradient elution with 1 mM ammonium formate and methanol. Data acquisition was performed on a QTrap 2000 tandem mass spectrometer in multiple reaction monitoring mode with positive electrospray ionization. Two transitions were monitored for each analyte in order to fulfill the established identification criteria. The validation included the determination of the limits of quantification (1.0 ng/mL for all analytes in serum and 2.0 ng/mL for all analytes in urine), assessment of matrix effects (77% to 92% in serum, 21 to 78% in urine) and the determination of extraction efficiencies (52% to 85% for serum, 59% to 88% for urine) and accuracy data. Imprecision was <10%, only the quantification of norclozapine in urine yielded higher relative standard deviations (11.2% and 15.7%). Bias values were below ±10%. Dilution of samples had no impact on the correctness for clozapine and norclozapine in both matrices and for clozapine-N-oxide in serum. For quantification of clozapine-N-oxide in urine a calibration with diluted calibrators has to be used. Calibration curves were measured from the LOQ up to 2,000 ng/mL and proved to be linear over the whole range with regression coefficients higher than 0.98. The method was finally applied to several clinical serum and urine samples and a cerebro-spinal fluid sample of an intoxicated 13-month-old girl.     

Ionization of Volatile Organics and Nonvolatile Biomolecules Directly from a Titanium Slab for Mass Spectrometric Analysis

Atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) and electrospray ionization (ESI)-MS can cover the analysis of analytes from low to high polarities. Thus, an ion source that possesses these two ionization functions is useful. Atmospheric surface-assisted ionization (ASAI), which can be used to ionize polar and nonpolar analytes in vapor, liquid, and solid forms, was demonstrated in this study. The ionization of analytes through APCI or ESI was induced from the surface of a metal substrate such as a titanium slab. ASAI is a contactless approach operated at atmospheric pressure. No electric contacts nor any voltages were required to be applied on the metal substrate during ionization. When placing samples with high vapor pressure in condensed phase underneath a titanium slab close to the inlet of the mass spectrometer, analytes can be readily ionized and detected by the mass spectrometer. Furthermore, a sample droplet (~2 μL) containing high-polarity analytes, including polar organics and biomolecules, was ionized using the titanium slab. One titanium slab is sufficient to induce the ionization of analytes occurring in front of a mass spectrometer applied with a high voltage. Moreover, this ionization method can be used to detect high volatile or polar analytes through APCI-like or ESI-like processes, respectively.     

Method validation and comparison of acetonitrile and acetone extraction for the analysis of 169 pesticides in soya grain by liquid chromatography–tandem mass spectrometry

An acetonitrile-based extraction method for the analysis of 169 pesticides in soya grain, using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in the positive and negative electrospray ionization (ESI) mode, has been optimized and validated. This method has been compared with our earlier published acetone-based extraction method, as part of a comprehensive study of both extraction methods, in combination with various gas chromatography–(tandem) mass spectrometry [GC–MS(/MS)] and LC–MS/MS techniques, using different detection modes. Linearity of calibration curves, instrument limits of detection (LODs) and matrix effects were evaluated by preparing standards in solvent and in the two soya matrix extracts from acetone and acetonitrile extractions, at seven levels, with six replicate injections per level. Limits of detection were calculated based on practically realized repeatability relative standard deviations (RSDs), rather than based on (extrapolated) signal/noise ratios. Accuracies (as % recoveries), precision (as repeatability of recovery experiments) and method limits of quantification (LOQs) were compared. The acetonitrile method consists of the extraction of a 2-g sample with 20 mL of acetonitrile (containing 1% acetic acid), followed by a partitioning step with magnesium sulphate and a subsequent buffering step with sodium acetate. After mixing an aliquot with methanol, the extract can be injected directly into the LC–MS/MS system, without any cleanup. Cleanup hardly improved selectivity and appeared to have minor changes of the matrix effect, as was earlier noticed for the acetone method. Good linearity of the calibration curves was obtained over the range from 0.1 or 0.25 to 10 ng mL⁻¹, with r² ≥ 0.99. Instrument LOD values generally varied from 0.1 to 0.25 ng mL⁻¹, for both methods. Matrix effects were not significant or negligible for nearly all pesticides. Recoveries were in the range 70–120%, with RSD ≤ 20%. If not, they were still mostly in the 50–70% range, with good precision (RSD ≤ 20%). The method LOQ values were most often 10 μg kg⁻¹ for almost all pesticides, with good repeatability RSDs. Apart from some minor pros and cons, both compared methods are fast, efficient and robust, with good method performances. The two methods were applied successfully in a routine analysis environment, during surveys in 2007 and 2008.     

Matrix effect in the analysis of drugs of abuse from urine with desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) and desorption electrospray ionization-mass spectrometry (DESI-MS)

We have studied the matrix effect within direct analysis of benzodiazepines and opioids from urine with desorption electrospray ionization-mass spectrometry (DESI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). The urine matrix was found to affect the ionization mechanism of the opioids in DAPPI-MS favoring proton transfer over charge exchange reaction. The sensitivity for the drugs in solvent matrix was at the same level with DESI-MS and DAPPI-MS (LODs 0.05–6 μg mL⁻¹) but the decrease in sensitivity due to the urine matrix was higher with DESI (typically 20–160-fold) than with DAPPI (typically 2–15-fold) indicating better matrix tolerance of DAPPI over DESI. Also in MS/MS mode, DAPPI provided better sensitivity than DESI for the drugs in urine. The feasibility of DAPPI-MS/MS was then studied in screening the same drugs from five authentic, forensic post mortem urine samples. A reference measurement with gas chromatography-mass spectrometry (GC–MS) (including pretreatment) revealed 16 findings from the samples, whereas with DAPPI-MS/MS after sample pretreatment, 15 findings were made. Sample pretreatment was found necessary, since only eight findings were made from the same samples untreated.     

Golf ball-assisted electrospray ionization of mass spectrometry for the determination of trace amino acids in complex samples

During the electrospray ionization (ESI) process, ions move through a heated capillary aperture to be detected on arrival at a mass analyzer. However, the ESI process creates an ion plume, which expands into an ion cloud with an area larger than that of the heated capillary aperture, significantly contributing to an ion loss of 50% due to coulombic repulsion. The use of DC and RF fields to focus ions from the ion source into the vacuum chamber has been proposed in the literature, but the improvement of ion transmission efficiency is limited. To improve ion transmission, in this study we propose a novel method using a home-made golf ball positioned between the ion source and the inlet of the mass analyzer to hydrodynamically focus the ions passing through the golf ball. The ion plume produced by the ESI process passes through the golf ball will reduce the size of the ion cloud then be focused and most of them flowed into the mass analyzer. Therefore, the sensitivity will be improved, the aim of this investigation is to study the enhancing of the signal using golf ball-assisted electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine 20 trace amino acids in complex samples, including tea, urine and serum. The results showed that the analytical performance of the determination of the 20 amino acids in tea, urine and serum samples using the home-made golf ball-assisted ESI source is better than that of a commercial ESI source. The signal intensities of the 20 amino acids were enhanced by factors of 2–2700, 11–2525, and 31–342680 in oolong tea, urine and serum analyses, respectively. The precision of the proposed method ranged from 1–9%, 0.4–9% and 0.4–8% at low, medium and high concentration levels of amino acids, respectively. The home-made golf ball-assisted ESI source effectively increased the signal intensity and enhanced the ion transmission efficiency and is also an easy, convenient and economical device. This technique can be applied to the analysis of trace compounds in complex matrices.     

LC/MS and LC/MS/MS based protocol for identification of dyes in historic textiles

Identification of dyes in historic textiles was until recently only based on reversed phase liquid chromatography and diode-array detection (RPLC–DAD). Although in the last years mass spectrometry (MS) is increasingly used as a detection system for liquid chromatography, most applications in the field are directed to identification of the molecular ions or in studies dedicated to degradation products which may be used as markers in RPLC–DAD. In the present work, an analytical protocol for the identification of dyes using RPLC/ESI/MS is presented. Atmospheric pressure electrospray ionization (ESI) was applied, in the negative ion monitoring mode. Both single stage and tandem MS (MS/MS) approaches were considered. An ion trap was used as mass analyzer. Experiments are based on the characterization of standards (natural dyes and/or dyed fibers) with the mass spectrometer sequentially working in the following modes: single MS/full scan, followed by plotting chromatograms through ion extraction (IEC) according to mass/charge ratios corresponding to molecular ions; single MS/selected ion monitoring (SIM) mode; tandem MS/single reaction monitoring (SRM) mode; tandem MS/multiple reactions monitoring (MRM) or product ion scanning modes. A faster chromatographic separation could be applied as MS detection readily balanced the selectivity of the analytical process. In a case study, 11 dyes from 3 biological sources were detected in a 0.5 mg historic sample.     

Highly sensitive capillary electrophoresis-mass spectrometry for rapid screening and accurate quantitation of drugs of abuse in urine

The combination of capillary electrophoresis (CE) and mass spectrometry (MS) is particularly well adapted to bioanalysis due to its high separation efficiency, selectivity, and sensitivity; its short analytical time; and its low solvent and sample consumption. For clinical and forensic toxicology, a two-step analysis is usually performed: first, a screening step for compound identification, and second, confirmation and/or accurate quantitation in cases of presumed positive results. In this study, a fast and sensitive CE-MS workflow was developed for the screening and quantitation of drugs of abuse in urine samples. A CE with a time-of-flight MS (CE-TOF/MS) screening method was developed using a simple urine dilution and on-line sample preconcentration with pH-mediated stacking. The sample stacking allowed for a high loading capacity (20.5% of the capillary length), leading to limits of detection as low as 2 ng mL⁻¹ for drugs of abuse. Compound quantitation of positive samples was performed by CE-MS/MS with a triple quadrupole MS equipped with an adapted triple-tube sprayer and an electrospray ionization (ESI) source. The CE-ESI-MS/MS method was validated for two model compounds, cocaine (COC) and methadone (MTD), according to the Guidance of the Food and Drug Administration. The quantitative performance was evaluated for selectivity, response function, the lower limit of quantitation, trueness, precision, and accuracy. COC and MTD detection in urine samples was determined to be accurate over the range of 10–1000 ng mL⁻¹ and 21–1000 ng mL⁻¹, respectively.     

基于敞开式直接电离质谱技术的尿液中毒品检测北大核心CSCD

尿液作为一种易于获取的体内毒品检材,在吸毒人员快速筛查中被广泛应用。针对传统快速筛查技术存在假阳性率高、定量能力不足以及实验室质谱技术在快速检测中存在前处理复杂、检测耗时长、使用环境苛刻等问题,该文提出了一种基于敞开式直接电离质谱技术的生物样本快速检测方法。该研究采用探针式电喷雾离子源与便携式质谱仪联用快速检测平台,优化了喷雾电压和质谱入口毛细管温度,开发了高效快速的前处理技术。基于该平台和前处理技术,5种常规毒品(甲基苯丙胺、氯胺酮、可卡因、O^(6)-单乙酰吗啡和3,4-亚甲双氧甲基苯丙胺)的尿液加标溶液的检出限为0.5~30 ng/mL,且其中4种毒品定量检测的线性相关系数大于0.99。除此之外,5种常规毒品在3个不同水平下的加标回收率为56.1%~103.7%,多次检测结果的相对标准偏差为9.0%~27.8%,说明联用检测平台与前处理方法结合可以达到良好的准确度。为了进一步检验该联用仪器的实战能力,测试了某社区戒毒康复中心40份阳性和110份阴性实际尿液样本,总体检测的准确率接近99%,且通过一次进样在20 s内可同时检测多种毒品。该研究成果有利于推动快速检测技术的发展,促进敞开式直接电离质谱仪技术的推广应用,提升一线执法服务水平。