Coupling Miniaturized Stir Bar Sorptive Dispersive Microextraction to Needle-Based Electrospray Ionization Emitters for Mass Spectrometry: Determination of Tetrahydrocannabinol in Human Saliva as a Proof of Concept.

Direct coupling of sample preparation with mass spectrometry (MS) can speed up analysis, enabling faster decision-making. In such combinations, where the analysis time is mainly defined by the extraction procedure, magnetic dispersive solid-phase extraction emerges as a relevant technique because of its rapid workflow. The dispersion and retrieval of the magnetic sorbent are typically uncoupled stages, thus reducing the potential simplicity. Stir bar sorptive dispersive microextraction (SBSDME) is a novel technique that integrates both stages into a single device. Its miniaturization (mSBSDME) makes it more portable and compatible with low-availability samples. This article reports the direct combination of mSBSDME and MS using a needle-based electrospray ionization (NESI) emitter as the interface. This combination is applied to determine tetrahydrocannabinol in saliva samples, a relevant societal problem if the global consumption rates of cannabis are considered. The coupling requires only the transference of the magnet (containing the sorbent and the isolated analyte) from the mSBSDME to the hub of a hypodermic needle, where the online elution occurs. The application of 5 kV on the needle forms an electrospray on its tip, transferring the ionized analyte to the MS inlet. The excellent performance of mSBSDME-NESI-MS/MS relies on the sensitivity (limits of detection as low as 2.25 ng mL-1), the precision (relative standard deviation lower than 15%), and the accuracy (relative recoveries ranged from 87 to 127%) obtained. According to the results, the mSBSDME-NESI-MS/MS technique promises faster and more efficient chemical analysis in MS-based applications.

Pre-cleaned bare wooden toothpicks for the determination of drugs in oral fluid by mass spectrometry.

This article deepens the potential of pre-cleaned bare wooden toothpicks (pb-WTs) for extracting drugs (antidepressants and acetaminophen) from oral fluid samples. The leaching of the intrinsic compounds from the wood matrix is identified as the main challenge for the final determination of the targets, even when a very selective instrumental technique, such as mass spectrometry, is employed. The pre-cleaning of the WTs is proposed for improving the analytical performance. The number of cleaning cycles depends on the injection mode (direct infusion or chromatography) into the mass spectrometer. The different variables affecting the extraction of selected antidepressant drugs were studied in detail, and the optimum procedure was validated using the two mentioned injection modes. The limits of detection were in the ranges 0.1-0.5 ng/mL and 0.1-0.3 ng/mL for direct infusion and liquid chromatography, respectively. The intra-day precision (expressed as relative standard deviation) was better than 12.1% and 8.6%, for direct infusion and liquid chromatography, respectively. Single-blind samples were used to study the applicability of the method. Finally, as a proof-of-concept, the potential of pb-WTs for in vivo sampling was outlined.

Wooden-based materials: Eco-friendly materials for direct mass spectrometric analysis and microextraction.

Lignocellulosic materials have arisen as a sustainable alternative in microextraction techniques during the last 10 years. As they are natural materials, their use fits into some of the principles of Green Analytical Chemistry. Their inherent porosity, narrow shape, and rigidity permit their use in ambient ionization mass spectrometry techniques. In particular, the combination of wooden-based materials and direct analysis gives birth to the so-called wooden-tip electrospray ionization mass spectrometry technique. This approach has been used for the direct analysis of complex samples, and as a streamlined tool for fingerprint quality analysis. Also, wooden-based materials can be superficially modified to boost the interaction with target compounds, allowing their isolation from complex samples. This review describes the potential and applicability of direct analysis using lignocellulosic materials, as well as other alternatives related to their use in microextraction.

Bioinspired composite packed in blunt needles, integrated microextraction and determination of oxycodone and naloxone in saliva by substrate spray mass spectrometry.

BACKGROUND: Opioids are effective painkillers used for medical purposes. Their prolonged ingestion can provoke some side effects (including overdose or constipation) that are minimized by using opioid antagonists (e.g., naloxone). The rapid determination of opioids and their antagonists in biosamples is essential for an effective medical treatment. The direct combination of sample preparation and mass spectrometry (MS) fits well in this scenario. It can speed up the analysis achieving a good selectivity, which relies on the sample preparation and MS, and sensitivity levels. RESULTS: This article presents a novel substrate-spray mass spectrometry interface based on a polydopamine-cotton (PDA-Cel) composite hosted inside the inner diameter of a 14-gauge blunt needle to determine oxycodone and naloxone in saliva samples. The needle is used as a microextraction device and a substrate for mass spectrometric analysis. The lack of sharpness of the 14-gauge (14G) blunt needles challenges the formation of the electrospray (ESI), and a commercial 10 µL pipette tip is proposed as a simple solution to this shortcoming. Under the optimum parameters, the proposed method was validated, obtaining limits of detection lower than 0.6 µg L-1, linear range up to 200 µg L-1, and linearity better than 0.9915. Relative standard deviation (RSD) and relative recoveries (RR) were studied at three different concentration levels (2, 40, and 200 µg L-1). RSD values were better than 20.7 %, and RR ranged from 90 to 114 %. Finally, a positive sample from a patient under medical treatment was analyzed. SIGNIFICANCE AND NOVELTY: 14G blunt needles have been demonstrated as effective extraction devices due to their low price (<0.15 € per extraction unit), their better safety (avoiding finger pricking), and their higher hosting capacity (up to 8 mg of sorbent). The conductivity of stainless steel permits their use as electrospray emitters, making their direct combination to MS easier. The large variety of fibrous sorbents makes this approach versatile enough to be adapted to other analytical problems.

Nylon 6-cellulose composite hosted in a hypodermic needle: Biofluid extraction and analysis by ambient mass spectrometry in a single device.

This study proposes a hypodermic needle (HN) as a sorbent holder and an electrospray (ESI) emitter, thus combining extraction and analysis in a single device. A novel nylon 6-cellulose (N6-Cel) composite sorbent is proposed to extract methadone from oral fluid samples. The cellulosic substrate provides the composite with high porosity, permitting the flow-through of the sample, while the polyamide contributes to the extraction of the analyte. The low price of the devices (considering the holder and the sorbent) contributes to the affordability of the method, and their small size allows easy transportation, opening the door to on-site extractions. Under the optimum conditions, the analyte can be determined by high-resolution ambient ionization mass spectrometry at a limit of detection (LOD) as low as 0.3 µg/L and precision (expressed as relative standard deviation, RSD) better than 9.3%. The trueness, expressed as relative recovery (RR), ranged from 90% to 109%. As high-resolution mass spectrometers are not available in many laboratories, the method was also adapted to low-resolution spectrometers. In this sense, the direct infusion of the eluates in a triple quadrupole-mass spectrometry provided an LOD of 2.2 µg/L. The RSD was better than 5.3%, and the RR ranged from 96% to 121%.

Volumetric absorptive microsampling for the therapeutic drug monitoring of psychiatric patients treated with cariprazine.

Psychiatric disorders are usually treated with antipsychotic agents belonging to different pharmacological and chemical classes, the most recent ones collectively known as "third-generation antipsychotics", such as cariprazine, approved in 2015 for the treatment of patients affected by schizophrenia. For these patients, a frequent therapeutic drug monitoring (TDM) becomes essential to assess compliance and to optimise and personalise their therapy, also due to cariprazine interindividual variability and narrow therapeutic range. In this study, a bioanalytical method featuring miniaturised sampling and pretreatment was developed, based on volumetric absorptive microsampling (VAMS) for TDM of psychiatric patients under cariprazine treatment and compared to a reference method based on fluid plasma analysis. Minimally invasive whole blood VAMS was coupled to an original instrumental method based on ultra-high performance liquid chromatography hyphenated to mass spectrometry (UHPLC-MS). A feasible and streamlined, yet reliable VAMS pretreatment protocol was carefully optimised and the VAMS-UHPLC-MS methodology was validated with satisfactory results in terms of linearity (r2 > 0.9970 in the 1.5-100 ng/mL range), precision (%RSD < 11.7), extraction yield (> 90.0 %) and matrix effect (8.2 ≤ %RE ≤ 10.9). Finally, the microsampling approach coupled to UHPLC-MS was successfully applied to the TDM of psychiatric patients treated with cariprazine and compared with standard fluid plasma analysis, providing reliable quali-quantitative results, and proving to be readily applicable to the clinical practice in TDM programs as a useful alternative to cariprazine plasma analysis. This is the first report of a successful microsampling application, and in particular the first report of VAMS application, for the TDM of cariprazine.

Polydopamine inner wall-coated hypodermic needle as microextraction device and electrospray emitter for the direct analysis of illicit drugs in oral fluid by ambient mass spectrometry.

In this article, polydopamine inner wall-coated hypodermic needles (PDA-HNs) are evaluated as both microextraction devices and electrospray ionization (ESI) emitters for determining selected illicit drugs (methamphetamine, cocaine, and methadone) in oral fluid samples. The PDA film, located in the inner wall of the needle, allows the extraction of the analytes at alkaline pH, where their hydrophobic character is promoted. The extracted analytes are finally eluted in a methanol/formic acid mixture that also acts as ESI solution. For this purpose, a dedicated interface based on the connection of a PEEK tube with the needle hub is proposed. This assembly allows delivering the ESI solution by the infusion syringe pump of the mass spectrometer, providing an efficient ESI on the tip of the needle. The double use of the PDA-HNs as microextraction devices and ESI emitters permits the determination of the target analytes with limits of detection and precision (expressed as relative standard deviation) values better than 2.4 µg/L and 17.6%, respectively. The accuracy was evaluated by analyzing independent spiked oral fluid samples, obtaining good results.