This study develops a chiral LC-MS/MS method with pre-column derivatization for simultaneous determination of carnitine (CAR) and acetylcarnitine (ACA) enantiomers in food. Conversion to 3-nitrophenylhydrazine derivatives followed by separation on a CHIRALPAK ZWIX (−) column provided resolution values above 1.57 for the respective enantiomers.After validation, the method was applied to meat, milk, and fermented soybean products. L-CAR and L-ACA were detected in all tested foods, while trace amounts of D-CAR were identified in the traditional Japanese fermented food Hama-natto, demonstrating the method’s suitability for selective food analysis.<blockquote><h4>The original article</h4><h4><a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#sec0010">Development of a chiral liquid chromatography-tandem mass spectrometry for simultaneous determination of carnitine and acetylcarnitine enantiomers in food samples</a></h4>Aogu Furusho, Hiroki Mizuno, Yutaro Nakayama, Eiji Sugiyama, Kenji Kojima, Kenichiro TodorokiJ. Pharm. Biomed. Anal. Open., 2026, 100111, Volume 7<div><a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#sec0010">10.1016/j.jpbao.2026.100111</a></div><h6>licensed under <a target="_blank" rel="noopener noreferrer" href="https://creativecommons.org/licenses/by/4.0/">CC-BY 4.0</a></h6></blockquote>Selected sections from the article follow. Formats and hyperlinks were adapted from the original.<div><div><div><div><div>Carnitine (CAR) is a functional endogenous compound found in various animals <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib1">[1]</a>. Since CAR has one asymmetric carbon in its structure, the l- and d-enantiomers are present. l-CAR is a cofactor that transports long-chain fatty acids into the mitochondria and promotes energy production via β-oxidation <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib2">[2]</a>. Humans biosynthesize 25% of the required amounts of l-CAR from l-lysine and l-methionine and ingest the remaining 75% from foodstuffs <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib3">[3]</a>, <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib4">[4]</a>. The insufficient intake of l-CAR induces a CAR deficiency <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib5">[5]</a>, and levocarnitine (l-form) is used as the therapeutic drug. Acetylcarnitine (ACA) is an acetylated molecule of CAR and is converted from CAR by carnitine O-acetyltransferase in the human body <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib6">[6]</a>. ACA is also related to energy production and is essential for storing acetyl groups to produce acetylcholine <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib7">[7]</a>. A previous study demonstrated that l-ACA taken from foods was partially hydrolyzed in the body and increased the l-CAR concentration within the tissues of aged rats <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib8">[8]</a>, indicating that CAR and ACA are interconverted. Furthermore, l-ACA has some therapeutic effects to downregulate inflammation-induced angiogenesis <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib9">[9]</a> and to reduce nerve pain <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib7">[7]</a>, <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib10">[10]</a>, making it a promising drug candidate. Both CAR and ACA are also commercially available as supplements to reduce body fat.Meanwhile, the d-isomers don’t have the above functions and are not thought to be present in the human body. Previous studies have revealed some specific functions such that d-CAR inhibited the l-CAR absorption causing CAR deficiency <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib11">[11]</a>, and d-ACA enhanced the efficiency of the drug for the Pompe disease <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib12">[12]</a>. Since the physiological actions of the d-forms and l-forms differ, enantioselective analysis of the CAR and ACA enantiomers is desirable for studying their functions and biokinetics.Several analytical methods have been already developed for the determination of the CAR and ACA enantiomers. In these methods, two approaches were mainly taken; i.e., the reversed-phase separation with the combination of diastereomeric derivatization and the direct separation by an enantioselective column. To convert enantiomers to diastereomers, chiral reagents, such as (+)-1-(9-fluorenyl)ethyl chloroformate <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib13">[13]</a> and l-alanine-β-naphthylamide <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib14">[14]</a>, were used. The conventional ODS column successfully separated the CAR and ACA enantiomers as their diastereomeric derivatives, and the methods were reported to be applicable for the enantiomeric purity check of drug substances. Regarding the chiral liquid chromatographic (LC) method, various types of enantioselective columns have been tested, but it was revealed that the separation of the CAR and ACA enantiomers was quite difficult <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib15">[15]</a>. A CHIRALCEL OD-R column based on the polysaccharide structure was among the few that achieved simultaneous separation of the CAR and ACA enantiomers. The target analytes were derivatized with (α-bromo)methyl phenyl ketone, and the method was applied to the analysis of drug substances <a style="color:rgb(2, 114, 177);font-size:16px;line-height:26px;text-decoration:none;" target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S2949771X26000101#bib16">[16]</a>. However, the measurement of foods, pharmaceutical agents, and biological samples has scarcely been performed, likely due to the low selectivity of the LC separation and ultraviolet/fluorescence detection used in these methods. Thus, improving the selectivity of the method is required to expand the range of the measurable samples.In the present study, a chiral LC-tandem mass spectrometric (MS/MS) method has been developed for the simultaneous determination of the CAR and ACA enantiomers. Direct separation using an enantioselective column enables the analysis independent of the optical purity of the reagents, and MS/MS could provide a higher selectivity than those of the previous methods. Furthermore, because CAR and ACA possess an ammonium cation which contributes to the high ionization efficiency, a high sensitivity by MS could also be expected. After the method development and validation, the content analyses of the CAR and ACA enantiomers were performed for meat, milk, and soybean fermented food samples.<h4>2. Experimental</h4><h5>2.4. LC-MS conditions</h5>The LC-MS/MS system consisted of ultra-high performance liquid chromatographic systems (<a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/en-us/all/products/198">ACQUITY H-class</a> and<a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/en-us/all/products/199"> I-class</a>, Waters, Milford, MA, USA) and triple quadrupole mass spectrometers (<a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/en-us/all/products/212">Xevo TQ-S</a> and <a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/en-us/all/products/209">TQ-S micro</a>, Waters). The chiral separation of CAR and ACA was performed on a CHIRALPAK ZWIX (-) column (3.0 mm I.D.×250 mm, 3 µm, Daicel Corporation, Osaka, Japan) at room temperature. The mobile phases were 5 mM FA/NH4FA in H2O/MeOH/MeCN (A: 2/9/89 and B: 2/19/79, v/v/v) at the flow rate of 0.25 mL/min. The LC gradient property was as follows: 0–25 min, 100% A; 25.1–45 min, 100% B; 45.1–60 min, 100% A. The MS detection was performed with the following conditions: 3.0 kV spray voltage for ESI positive ionization; 150 L/hr cone gas flow rate; 1000 L/hr desolvation gas flow rate; 150°C source temperature; 500°C desolvation temperature. The selected reaction monitoring (SRM) mode was used for the detection, and the set transitions, cone voltage (CV), and collision energy (CE) for the target compounds are summarized in Table 1. The different CEs were used for 3-NPH-ACA on Xevo TQS (10 eV) and Xevo TQ-S micro (20 eV). Data processing was performed using <a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/en-us/all/products/635">MassLynx v4.2 software</a> (Waters).<h4>3. Results and discussion</h4><h5>3.4. Determination of the CAR and ACA enantiomers in food samples</h5>The developed method was applied to the analysis of the CAR and ACA enantiomers in food samples. CAR and ACA are known to be abundant in animal-based foods [23], thus, beef, pork, chicken, and milk were measured. The measured cuts of meat were the shank for beef, thigh for pork, and thigh for chicken in this study, and these parts are commonly used in commercially-available ground meats. Fermented foods are reported to contain relatively high levels of d-amino acids, and some of them are considered to be produced by bacteria during the fermentation process [24]. To investigate the production of CAR and ACA by bacteria, three fermented foods made from soy beans (miso, soy sauce, and Hama-natto) were analyzed. Hama-natto is a traditional food from the Hamamatsu City area in Shizuoka Prefecture, Japan. Steamed soybeans are fermented with koji mold, then salted and dried in the sun.The chromatograms of the beef and Hama-natto samples are shown in Fig. 4. l-CAR and l-ACA were clearly observed in both samples. The l-forms were also found in the other tested samples, and their quantified values are summarized in Table 4. Comparing the amounts of l-CAR in the meat samples, beef had the highest levels, followed by pork and chicken. The l-ACA levels were also the highest in beef, and chicken contained more than pork.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/J_Pharm_Biomed_Anal_Open_2026_100111_Volume_7_Fig_4_Determination_of_the_CAR_and_ACA_enantiomers_in_beef_56d92bf289.jpg" alt="J. Pharm. Biomed. Anal. Open., 2026, 100111, Volume 7: Fig. 4. Determination of the CAR and ACA enantiomers in beef and Hama-natto samples as their 3-NPH derivatives. The selected ion chromatogram of ACA is shown for 0–30 min, and that of CAR is shown for 30–60 min." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_J_Pharm_Biomed_Anal_Open_2026_100111_Volume_7_Fig_4_Determination_of_the_CAR_and_ACA_enantiomers_in_beef_56d92bf289.jpg 245w," sizes="100vw" width="2247" height="542"><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/J_Pharm_Biomed_Anal_Open_2026_100111_Volume_7_Table_4_Amounts_of_l_CAR_and_l_ACA_in_the_food_samples_1c2411fe51.jpg" alt="J. Pharm. Biomed. Anal. Open., 2026, 100111, Volume 7: Table 4. Amounts of l-CAR and l-ACA in the food samples." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_J_Pharm_Biomed_Anal_Open_2026_100111_Volume_7_Table_4_Amounts_of_l_CAR_and_l_ACA_in_the_food_samples_1c2411fe51.jpg 245w," sizes="100vw" width="981" height="447"><h5>3.5. Confirmation of D-CAR in the Hama-natto sample</h5>To confirm the presence of d-CAR in the Hama-natto, four approaches were conducted; i.e., remeasurement of the fraction, detection with a different SRM transition, separation under different LC conditions and use of high-resolution MS. The fraction was placed in a 1.5 mL tube for three min before the MS to purify the d-CAR. The solution (total 750 µL) was dried and dissolved in 50 µL of the mobile phase. The chromatogram obtained by the remeasurement is shown in Fig. 5A, and the result detected by a different SRM transition (297.1 &gt; 102.1) is in Fig. 5B. The peak of d-CAR was clearly observed in both measurements, and the peak shapes were similar. However, the amount of d-CAR was under the LLOQ and could not be quantified. As shown in Fig. 5C, d-CAR was also detected using the different LC conditions described in Section 2.6, suggesting that the peak was definitely derived from the d-CAR. A high-resolution MS analysis detected a molecule with m/z 297.155, which closely matched with the exact mass of 3-NPH-CAR (m/z 297.156). The extracted ion chromatogram of that molecule is shown in Fig. 5D, and the d-CAR peak was clearly observed. These results demonstrated that trace amounts of d-CAR were present in the Hama-natto sample. To the best of our knowledge, this is the first report to find natural d-CAR in foods. One possible origin of this d-CAR is a production by bacteria including koji mold. Some bacteria are known to produce d-amino acids for cell wall formation [32]. The bacteria capable of producing d-CAR may exist and be involved in the fermentation of Hama-natto. Since the l-CAR and l-ACA concentrations in the other fermented foods were lower than that in Hama-natto, there is a possibility to also detect the d-forms from other foods by the improvement of the extraction process. Further research using various food samples is expected.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/J_Pharm_Biomed_Anal_Open_2026_100111_Volume_7_Fig_5_Chromatograms_of_the_3_NPH_d_CAR_fractions_2c9fbf4df7.jpg" alt="J. Pharm. Biomed. Anal. Open., 2026, 100111, Volume 7: Fig. 5. Chromatograms of the 3-NPH-d-CAR fractions analyzed by the different analytical methods. The SRM transitions were 297.1 &gt; 102.1 (A) and 145.1 (B). The fraction was analyzed by LC-MS/MS under the different conditions (C) and LC-TOF-MS (D). The detailed analytical conditions are described in Section 2.6." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_J_Pharm_Biomed_Anal_Open_2026_100111_Volume_7_Fig_5_Chromatograms_of_the_3_NPH_d_CAR_fractions_2c9fbf4df7.jpg 245w," sizes="100vw" width="2663" height="1199"><h4>4. Conclusion</h4>In the present study, a chiral LC-MS/MS method has been developed for the simultaneous determination of the CAR and ACA enantiomers in food samples. The derivatization with 3-NPH extended the retention time and improved the enantiomeric separations especially for CAR. The validated method was successfully applied to the analysis of meat, milk, and soybean fermented food samples, and trace amounts of d-CAR were discovered in Hama-natto. The present method is able to distinguish enantiomers in various samples and can contribute to clarifying the origin of d-CAR in food samples and searching/developing for new functional food products.</div></div></div></div></div>

Development of a chiral liquid chromatography-tandem mass spectrometry for simultaneous determination of carnitine and acetylcarnitine enantiomers in food samples

When NIST26 processes LC-MS/MS data in the Chromatogram Window, the final list of compound identifications is only one part of the story. Behind the results displayed in the software lies an entire group of intermediate files containing chromatographic traces, extracted MS/MS spectra, search results, isotope information, peak models and associations between chromatographic features and spectra. In a recent <a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/pdf/identifications_raw_files_28359b66de.pdf">handout</a>, James Little of Mass Spec Interpretation Services examined what these files represent, how they relate to the new XIC-centric processing workflow in NIST26, and what additional information they may offer to analysts. identifications-raw-filesThe starting point is the Identifications folder created when an LC-MS/MS file is processed in the NIST26 Chromatogram Window. Rather than producing a single result file, the software generates a group of intermediate outputs associated with MS/MS deconvolution and library searching. These data are subsequently used to construct the information formally presented in the Chromatogram Window. The handout also explores whether some of these outputs could have value beyond the immediate identification workflow, for example as inputs for multivariate analysis or sample comparison. identifications-raw-files<h4>An XIC-centric approach to LC-MS/MS processing</h4>The workflow described in the presentation is built around extracted ion chromatograms (XICs). Instead of treating every MS/MS spectrum as an isolated identification event, NIST26 relates spectral information back to chromatographic behavior.The workflow first extracts chromatographic information from MS1 data, groups spectra according to retention time, associates MS/MS spectra with XIC peaks and then uses this information to validate or refine identifications. The diagrams on pages 8–15 of the handout illustrate this as a multistep process rather than a simple “MS/MS spectrum → library match → identification” sequence. identifications-raw-filesThis distinction is important because the chromatographic dimension provides additional evidence. A candidate identification can be evaluated not only from its MS/MS library match, but also according to whether the associated precursor behaves consistently in the chromatogram, whether its isotopic pattern makes sense and whether the MS/MS spectrum is correctly linked to the relevant chromatographic peak.<h4>Parallel processing generates multiple intermediate files</h4>One reason the Identifications folder contains so many files is that NIST26 divides the raw mzML dataset into multiple chunks for parallel processing. Each chunk generates its own intermediate outputs.The presentation describes several important file types. The .tic files contain total ion chromatogram information based on MS1 intensity versus retention time and are used for processes such as peak detection, retention-time alignment and XIC windowing. The .mgf files contain peak-picked MS/MS spectra in Mascot Generic Format and serve as inputs for library searching. The .tsv files contain tabulated search results, including candidate identifications and associated scores and precursor information. identifications-raw-filesThese intermediate files therefore correspond to different levels of the processing workflow: chromatographic information from MS1, spectral information from MS2, library-search results and the subsequent cross-validation of these layers.<h4>From thousands of spectra to the final reported identifications</h4>The handout gives a useful example of how strongly the dataset can be reduced during processing.In the example discussed, the original mzML file contained 3,380 spectra, which were divided into four processing chunks. From these data, 216 tandem MS/MS spectra were extracted for library searching. Ultimately, 158 MS2 searches survived into the final displayed or reportable results. According to James Little's note, processing those 158 spectra took approximately 11 seconds. identifications-raw-filesThis illustrates that the final result table represents only a selected subset of the spectral information originally present in the file. The intermediate outputs preserve information about how that subset was generated.<h4>What is inside the “check” files?</h4>A central point of the presentation is that the files informally referred to as “check” files are not simply temporary clutter. Conceptually, they form an intermediate evidence layer between the original MS/MS library search and the final identification.According to the workflow shown in the handout, these files may contain XIC traces for individual precursor ions, isotope traces, peak models, retention-time associations, in-source ion relationships and grouping information describing which MS/MS spectra belong to which chromatographic peaks. identifications-raw-filesThe workflow can therefore use chromatographic evidence to confirm or reject candidate identifications, refine precursor assignments and distinguish useful MS/MS spectra from background signals. The presentation contrasts this with a more traditional workflow in which an MS/MS library match might effectively represent the end of the identification process. In the NIST26 XIC-centric approach, the sequence becomes closer to MS/MS search → identification candidate → XIC validation → refinement and re-ranking. identifications-raw-files<h4>Chromatographic information adds another layer of confidence</h4>The practical value of this additional processing lies in combining information that would otherwise be considered separately.An MS/MS spectrum may produce a convincing library match, but NIST26 can additionally examine whether the precursor generates a coherent chromatographic peak, whether the expected isotopic signals appear together and whether the retention-time relationships are consistent. The internal datasets can also help track in-source fragments, which could otherwise be interpreted as independent compounds.The final slide of the handout summarizes these files as the core evidence layer of the new NIST approach, containing chromatographic information, isotope behavior, retention-time consistency and in-source relationships. According to the presentation, these data help correct precursor assignments, recognize in-source fragments and improve overall MS/MS identification confidence. identifications-raw-files<h4>Can the outputs be used beyond compound identification?</h4>Another interesting question raised in the presentation is whether the information generated during NIST26 processing could be reused for other data-analysis tasks.The .tsv output generally contains one row per detected chromatographic feature and may include retention time, precursor m/z, peak area or intensity, library-match score, compound name, molecular formula and adduct information where available. identifications-raw-filesThe handout suggests that this type of tabular output could provide a useful starting point for building a feature matrix for downstream analyses such as:<ul><li>principal component analysis (PCA),</li><li>hierarchical clustering,</li><li>comparison of “good” and “bad” samples,</li><li>outlier detection,</li><li>and marker discovery. identifications-raw-files</li></ul>Importantly, this part of the handout is presented as an exploration of possible utility rather than as a formally demonstrated NIST26 workflow. James Little notes that ChatGPT was used to examine the relationships among the generated files and consider how they might potentially be used. identifications-raw-files<h4>Why does NIST26 create so many files?</h4>The large number of intermediate files is ultimately a consequence of two characteristics of the processing strategy: parallelization and multi-level analysis.The raw data are split into several chunks to accelerate computation, while separate data products are generated for MS1 chromatographic processing, MS2 spectral searching and subsequent cross-validation. The workflow therefore preserves intermediate evidence at several stages rather than collapsing everything immediately into a single final result table.The result is a folder that can initially appear unnecessarily complex, but which reflects the architecture of the analysis itself. As emphasized in the handout, the intermediate files are not simply processing leftovers; they document how chromatographic and mass-spectral information was combined to arrive at the final identification. identifications-raw-files<h4>More than a library search</h4>The main message of the presentation is that the new NIST26 LC-MS/MS workflow goes beyond conventional spectrum-to-library matching. By incorporating XIC behavior, isotope information, peak relationships, retention-time consistency and MS/MS evidence, the software can use multiple independent pieces of information to evaluate an identification.For analysts, understanding what is stored in the Identifications folder provides a clearer picture of how the final results are generated. It also opens the possibility of inspecting intermediate processing steps when troubleshooting questionable identifications and, potentially, reusing some of the tabulated feature-level outputs for broader sample-comparison workflows.The growing importance of these intermediate datasets also reflects a wider shift in LC-MS/MS analysis: confident identification increasingly depends not on a single score or spectrum, but on the combined interpretation of chromatographic, spectral and contextual evidence.

Identifications Folder: Raw Files Created in MS/MS NIST26

At UC San Diego, researchers are using patient-derived brain organoids and spaceflight to explore whether aging-associated biology can be accelerated in orbit. With advanced proteomics enabled by the Thermo Scientific Orbitrap Astral Mass Spectrometer (MS), the team is gaining deeper insight into complex brain biology and new possibilities for studying neurodegenerative disease.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Neuroscience_Takes_Flight_How_Collaboration_Spaceflight_and_Orbitrap_Astral_MS_Are_Opening_a_New_Window_into_Brain_Aging_6b56e04145.webp" alt="Thermo Fisher Scientific: Neuroscience Takes Flight: How Collaboration, Spaceflight, and Orbitrap Astral MS Are Opening a New Window into Brain Aging" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Neuroscience_Takes_Flight_How_Collaboration_Spaceflight_and_Orbitrap_Astral_MS_Are_Opening_a_New_Window_into_Brain_Aging_6b56e04145.webp 245w," sizes="100vw" width="1024" height="512"><h3>Introduction</h3>Neurodegenerative diseases remain among the most difficult conditions to study. Researchers cannot easily or safely biopsy living brain tissue, and even sophisticated disease models can take years to reveal meaningful biological change. At UC San Diego, Drs. Aline Martins and Alysson Muotri are taking a different approach: creating patient-derived brain organoids from skin cells and sending them to space to explore whether low Earth orbit can accelerate aging-associated biology. Preliminary data suggest that 30 days in space may compress roughly 10 years of aging biology into a much shorter experimental window, opening the door to a faster path for understanding neurodegeneration and evaluating new therapeutic ideas.<h3>A study design built around biology</h3>The real power of this work begins with the study design. Rather than relying on generalized models, the researchers begin with skin cells from patients and generate 3D mini-brain organoids that can model diseases such as Alzheimer’s while preserving critical patient context. That gives the team a more human-relevant system for studying how aging and disease unfold over time. Spaceflight adds a second dimension: a research environment that is exceptionally difficult to reproduce on Earth, but one that may help reveal the molecular and cellular drivers of neurodegeneration faster than conventional studies allow. The Integrated Space Stem Cell Orbital Research (ISSCOR) Center at UC San Diego have begun to explore this broader approach to study how space-related stressors influence brain aging and cognitive decline, with potential relevance to diseases such as Alzheimer’s and dementia. Once those organoids return to Earth, the next challenge is extracting as much insight as possible from every sample.<h3>Enabling deeper insight from limited samples</h3>Brain organoids are inherently heterogeneous, with multiple cell subtypes that may respond differently to aging and environmental stress.To extract deeper biological insight from the organoid samples, the researchers describe the<a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/en-us/all/products/836"> Orbitrap Astral MS </a>as central to their investigation. They highlight that the high sensitivity required for single-cell proteomics is essential for revealing how the space environment affects distinct cell populations and the Orbitrap Astral MS helps unlock deeper biological insight.That distinction is important: the value of the Orbitrap Astral MS analytical workflow is not simply generating more data but importantly helping the team resolve more of the biology within a complex model.<h3>How Orbitrap Astral MS helps push biology further</h3>At Thermo Fisher Scientific, we work alongside researchers pursuing bold scientific questions by developing technologies that help them see deeper into complex biology.Aline describes Orbitrap Astral MS as a major advance for the sensitivity and resolution this research requires. Its synchronized data acquisition capabilities and parallel ion processing across dual high-resolution accurate-mass analyzers with maximized instrument utilization help deliver deeper coverage, higher sensitivity, faster throughput, and accurate, precise quantitation across demanding biological workflows.For studies like this one, those capabilities help researchers get more from limited sample material, uncover subtle disease-relevant changes, and translate an inventive experimental design into deeper biological insight, faster.<h3>Looking ahead</h3>The power of this research lies in the convergence of ideas. Patient-derived brain organoids offer a human-relevant model of disease. Spaceflight may serve as an aging accelerator. Advanced proteomics helps researchers understand what complex biological models are revealing with greater depth and clarity, while single-cell proteomics unlocks a view into cell-specific changes that can drive disease biology. Together, this approach could give scientists a faster and more informative way to study late-onset diseases such as Alzheimer’s and dementia. This initiative between UC San Diego and Thermo Fisher Scientific shows how collaborations across the scientific community can open new doors in neuroscience and accelerate discovery in ways that matter. As researchers continue to push the boundaries of what is possible, studies like this one point to a future where deeper biological insight can be reached faster and with greater potential to improve human health.<h3>Learn more</h3><ul><li>Listen to the <a target="_blank" rel="noopener noreferrer" href="https://corporate.thermofisher.com/us/en/index/newsroom/Our-stories/Brains-in-space.html">interview with Dr. Aline Martins</a> for more on the scientific vision behind this research and its implications for brain aging and neurodegenerative disease.</li><li>Learn more about <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/mass-spectrometry/proteomics-mass-spectrometry/single-cell-proteomics.html">Thermo Fisher Scientific single-cell proteomics solutions</a> and how they help researchers gain deeper insight from limited and complex samples.</li><li>Explore the <a target="_blank" rel="noopener noreferrer" href="https://labrulez.com/en-us/all/products/836">Thermo Scientific Orbitrap Astral MS</a> and see how it helps researchers achieve deeper biological insight with faster throughput, higher sensitivity, and accurate, precise quantitation across advanced workflows.</li></ul><blockquote>Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#BrainOrganoids #SpaceBiology #Neurodegeneration #OrbitrapAstralMS</blockquote>

Neuroscience Takes Flight: How Collaboration, Spaceflight, and Orbitrap Astral MS Are Opening a New Window into Brain Aging

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This webinar will provide tips and tricks on troubleshooting in titration.

Titration: Troubleshooting

This webinar will provide tips and tricks on troubleshooting in titration.

Watch this webinar to learn about titration methods, titer determination, and sample preparation.

Titration: Fundamentals

Watch this webinar to learn about titration methods, titer determination, and sample preparation.

Titration is one of the most basic analytical methods for chemical analysis.
However, even power users sometimes struggle with the quality of their titrations. In this expert webinar, we explore the basics of volumetric titration and present tips and advice to help you make sure that your titration results are always precise and reproducible. The following topics will be addressed:
What is the most suitable titration method for my sample or sample matrix?
<ul>
<li>Photometric vs. potentiometric titration
</li>
<li>Direct vs. back (residual) titration
</li>
<li>End point vs. equivalent point titration
</li>
</ul>
Hardware selection
<ul>
<li>Sensor/burette size/stirrer</li>
</ul>
Reagent selection
<ul>
<li>Buffer solutions/titrant/standard reference reagents</li>
</ul>
Method development &amp; validation
<ul>
<li>Titration modes &amp; parameters
</li>
<li>Method validation (selectivity, linearity, accuracy &amp; reproducibility)
</li>
</ul>
Key learning objectives
<ul>
<li>How to select the proper hardware and the right chemistry for your titrations
</li>
<li>How to optimize titration performance depending on your application
</li>
<li>How to verify the suitability and accuracy of a titration method
</li>
<li>How to convert manual titration methods into automated procedures
</li>
</ul>
Who should attend?
This webinar will be of particular interest to people in charge of developing or qualifying volumetric titrations, especially lab technicians, lab managers and quality assurance professionals
<blockquote>
Presenter: Dr. Christian Haider (Head of Competence Center Titration, Metrohm AG)
</blockquote>
<blockquote>
Dr. Christian Haider joined Metrohm AG in the year 2002 as Application Specialist Titration. As Head of the Competence Center Titration he leads a team of product managers, product specialists and application chemists for all different titration techniques, pH and conductivity measurement, titration automation and software.
</blockquote>
<blockquote>
Presenter: Angela Schwehn (Chemical Laboratory Technician, Merck KGaA, Darmstadt, Germany)
</blockquote>
<blockquote>
Angela Schwehn is a chemical laboratory technician in the Life Science R&amp;D department at Merck KGaA, Darmstadt, Germany. She has more than 15 years of experience in modern volumetric titration and Karl Fischer titration and is responsible for the development of new reagents and standards in the field of volumetric titration and Karl Fischer titration.
</blockquote>
<blockquote>
Presenter: Sarah Thomas (Editorial Team, SelectScience)
</blockquote>
<blockquote>
Sarah studied biology at the University of Bath, UK, and has worked in the Pharmaceutical Sciences Department of St. Jude Children’s Research Hospital, Memphis. As a member of the Editorial team, Sarah plays an integral role in shaping the content on SelectScience.
</blockquote>
<blockquote>
Presenter: Ellie Abbott (Editorial Team, SelectScience)
</blockquote>
<blockquote>
Ellie studied biochemistry at the University of Nottingham, UK, and has previous experience working in management consultancy. As a member of the Editorial team, she now plays an integral role in shaping the content on SelectScience.
</blockquote>

Metrohm: Volumetric titration: A step-by-step guide to correct results

Volumetric titration: A step-by-step guide to correct results

The basics of volumetric titration and present tips and advice to help you make sure that your titration results are always precise and reproducible.

Volumetric titration: A step-by-step guide to correct result

In most laboratories, the age of manual titrations is over. Good so: Modern, digital autotitrators support users with various features that help reduce errors and optimize titration results.
However, even routine users are sometimes struggling with the basics, e.g., which kind of electrode to choose for which titration, which titration mode to select for which matrix, or how to make sure results are properly evaluated by the device.
In this presentation, we focus on how to get the basics of titration right so you can always trust your results:
<ul>
<li>How to select the right hardware for your titration (electrode, burette size, stirrer)
</li>
<li>How to handle your hardware properly (this is critical!)
</li>
<li>How to choose the correct settings and parameters on your autotitrator, depending on your matrix and method
</li>
<li>How endpoints are evaluated correctly and how to optimize endpoint evaluation
</li>
<li>Troubleshooting: What to do in case you get incorrect results
</li>
</ul>
This presentation is intended for all users of potentiometric titrators, chemists developing titration applications, laboratory managers – simply everyone who is interested in modern titration.
<blockquote>
Presenter: ChristianHaiderWebDr. Christian Haider (Head of Competence Center Titration, Metrohm AG)
</blockquote>
<blockquote>
Dr. Haider joined Metrohm AG in the year 2002 as Application Specialist Titration. As Head of the Competence Center Titration he leads a team of Product Managers, Product Specialists and Application Chemists for all different titration techniques, pH and conductivity measurement, titration automation and software.
</blockquote>

Metrohm: How to Improve Your Titration Results – Optimizing Performance and Troubleshooting

How to Improve Your Titration Results – Optimizing Performance and Troubleshooting

How to get the basics of titration right so you can always trust your results.

How to Improve Your Titration Results & Troubleshooting

Have you ever wondered how the quality of your sensor can influence your titration results?
In this webinar, Dr. Sabrina Gschwind, sensors product manager at Metrohm, will detail proper sensor maintenance and how you can check and monitor the performance of your unit. In addition, you will receive tips and tricks to increase the quality of your titration results and thus avoid wasting time on tedious root cause analysis and instrument downtime due to sensor failure.
Key Learning Objectives:
<ul>
<li>Learn which component of a sensor has which function
</li>
<li>Learn how to clean, maintain, and store the most commonly used titration sensors
</li>
<li>Understand how the sensor can influence your titration results
</li>
<li>Gain the know-how to overcome the most common titration errors
</li>
</ul>
Who should attend?
Everybody involved in performing potentiometric or photometric titrations and who wishes to gain more in-depth knowledge about which sensors to use, sensor maintenance, storage, as well as tips and tricks for best titration results.
<blockquote>
Presenter: Sabrina Gschwind (Product Manager Sensors, Metrohm AG)
</blockquote>
<blockquote>
Sabrina has been working at Metrohm International Headquarters for almost 5 years, initially in the application lab developing tailor-made applications. Since 2016, Sabrina has been the product manager responsible for the Metrohm sensor portfolio, which includes pH, metal and ion-selective electrodes, and photometric sensors as well as conductivity measuring cells. In this role, she is not only taking care of the entire product lifecycle, but also provides support and training for sensors.
</blockquote>
<blockquote>
Presenter: Dr. Matthew McArdle (Editor, SelectScience)
</blockquote>
<blockquote>
Matthew McArdle is a member of the editorial team at SelectScience and plays a key role in content production, specializing in molecular biology and biochemistry fields. He has a Ph.D. from Leeds University, where he researched the effects of promoter-driven gene expression on vascular smooth muscle cell growth.
</blockquote>

Metrohm: Avoid titration mistakes through best practice sensor handling

Avoid titration mistakes through best practice sensor handling

Proper sensor maintenance and how you can check and monitor the performance of your unit.

Avoid titration mistakes via best practice sensor handling

Perfect and fully traceable titration results require maximum synergy between the titration hardware and the reagents used – this is especially required when working under GxP conditions or in a regulated environment.
Is the titration performed with the correct equipment and reagents? Do the titration hardware and reagents qualify for the intended application? Have there been any deviations from normal routine? And, maybe most importantly, how can this all be proved, immediately before or during the titration, as well as later in your archived titration data?
In this webinar, Eyla Reuss (Merck KGaA) and Christian Haider (Metrohm AG) introduce you to the advantages of the unique combination of the Omnis titration platform with the jointly developed 3S titration reagents. Find out how automated transfer of relevant data ensures data integrity and traceability.
By viewing this presentation you will learn...
<ul>
<li>how modern titration hardware improves safety in the lab and can prevent handling or application errors
</li>
<li>how modern reagents leave no data gap for the reagents used
</li>
<li>how modern titration software can simplify your documentation and maintain data security and integrity
</li>
<li>how easy it is to track titration data to the manufacturer’s certificates
</li>
</ul>
Who should view this webinar?
Lab chemists, laboratory managers, quality control professionals, pharmaceutical industry professionals or simply everybody that is interested in titration.
<blockquote>
Presenter: Eyla Reuss (Merck KGaA)
</blockquote>
<blockquote>
As Chemical Laboratory Technician in the Life Science R&amp;D department, Eyla Reuss joined Merck in 2012 and is now responsible for new developments of reagents, standards and devices in the field of titration and Karl Fischer titration.
</blockquote>
<blockquote>
Presenter: Christian Haider (Metrohm AG)
</blockquote>
<blockquote>
Dr. Haider joined Metrohm AG in 2002 as Application Specialist Titration. He leads the Competence Center Titration that is specialized on all different titration techniques, pH and conductivity measurement, titration automation and software.
</blockquote>

Titration and Lab 4.0

The advantages of the unique combination of the Omnis titration platform with the jointly developed 3S titration reagents.

Titration and Lab 4.0 (Full Traceability & Data Integrity)

Separation Science, in collaboration with Metrohm, has developed an on-demand webinar covering the benefits of automating sample preparation for titration.
Stand-alone potentiometric or Karl Fischer titrations are a full-time job for lab technicians, as they have to do sample preparation, start the titration, dispose of the titrated solution, and rinse the titration equipment, followed by re-conditioning of the electrode prior to the next titration if requested.
Sample preparation includes the addition of solvents and auxiliary solutions, aliquoting of liquid samples, dissolution or homogenization of solids, filtration, or even more complex techniques, e.g., time-controlled pre-reactions with auxiliary reagents prior to titration. In addition, other chemical or physical properties of the sample such as consistency, poor solubility, hygroscopy, or possible side reactions may contribute to inconsistent results.
This on-demand webinar presents options and examples of how sample preparation for potentiometric and Karl Fischer titration can be fully automated and, therefore, be made safer, more efficient and more reproducible. Furthermore, the webinar shows how the whole titration workflow can be made much faster.
By viewing this on-demand webinar you will...
<ul>
<li>Learn how automation can eliminate manual handling of toxic reagents and waste solutions.
</li>
<li>Understand how automation increases reproducibility because all sample preparation steps are performed automatically.
</li>
<li>Learn how automation saves time and money because parallel operation allows for a higher throughput and frees up laboratory staff.
</li>
</ul>
The presentation is ideal for...
<ul>
<li>Anyone who is interested in automated titration systems and would like to know more about it.
</li>
<li>Lab technicians who want to reduce human errors during sample preparation and increase the safety handling aggressive reagents.
</li>
<li>Lab managers who are interested in time and money that could be saved by working with automated systems.
</li>
</ul>
<blockquote>
Presenter: Heike Risse (Product Manager Titration Automation, Metrohm)
</blockquote>
<blockquote>
Heike is Product Manager Titration Automation in the Competence Center for Titration at Metrohm International Headquarters, Herisau, Switzerland. She has worked with titration for more than 18 years at Metrohm. During this time, Heike worked as an Application Specialist Titration with focus on method and application development for all industries. For more than 13 years, she has been responsible for the product management of automated titration systems.
</blockquote>

Metrohm: Improve Titration Reproducibility and Efficiency with Automation

Improve Titration Reproducibility and Efficiency with Automation

Options and examples of how sample preparation for potentiometric and Karl Fischer titration can be fully automated.

Titration Reproducibility and Efficiency with Automation

Join us as we discuss the collaborative process that led from the introduction of Shimadzu’s Nexera UC analytical SFC systems to the Pharma-focused creation and launch of the Nexera UC Prep semi-preparative SFC systems.
We will explore the uses of SFC and see how the Shimadzu lineup has been shaped to meet the needs of Pharma SFC users through their direct input into instrument and software design and development.
<blockquote>
Presenter: Brian Domanski (Strategic Collaboration Scientist, Shimadzu Scientific Instruments)
</blockquote>
<blockquote>
Brian has over 10 years working to provide LC and SFC solutions for Pharma, as well as experience with a wide range of chromatography techniques including RP, NP, HILIC, IEX, SEC/GPC, and IC. His focus also includes scalable Informatics and Data Integrity solutions.
</blockquote>

Shimadzu: Harnessing the Power of Collaboration: Shimadzu’s SFC Journey

Harnessing the Power of Collaboration: Shimadzu’s SFC Journey

Collaborative process that led from the introduction of Shimadzu’s Nexera UC analytical SFC systems to the Pharma-focused creation.

Shimadzu’s SFC Journey

Traditionally, LC/MS for large molecule drug analysis required an enzymatic digestion to cleave larger proteins into smaller peptides more amenable to mass analysis. The disadvantages to this approach are many and include low throughput, incomplete enzymatic reaction, and surrogate peptide bias due to modifications in the molecules. Modern mass spectrometers have allowed researchers to analyze large molecules at their intact level.
We demonstrate an automated LC/MS workflow to quantify intact mAb drugs in mouse plasma. The workflow uses an Agilent AssayMAP Bravo automated liquid handling platform and an Agilent 6545XT AdvanceBio LC/Q-TOF system. Our results show that this automated LC/MS assay can be used for quantitative analysis of biologic therapeutics with excellent sensitivity and reproducibility.
<blockquote>
Presenter: Xi Qiu, PhD (LC-MS Application Scientist, Agilent Technologies, Inc.)
</blockquote>
<blockquote>
Xi Qiu is application scientist at Agilent, he earned his Ph.D. degree from the department of Pharmacognosy and Medicinal Chemistry at University of Illinois at Chicago. Prior to joining Agilent, he worked at Johnson and Johnson where he focused on large molecule quantification using LC-MS at intact and peptide level as well as contract research organizations leading large molecule LC-MS group performing protein, protein conjugates, peptide, and oligos analysis.
</blockquote>

Agilent Technologies: Ultra-Sensitive Intact Monoclonal Antibody Quantification Using a Liquid Handling Platform and a LC/Q-TOF Mass Spectrometer

Ultra-Sensitive Intact Monoclonal Antibody Quantification Using a Liquid Handling Platform and a LC/Q-TOF Mass Spectrometer

Learn how to utilize superior resolving power to achieve in depth characterization of therapeutic antibodies at protein, subunit and peptide level using the novel capillary Thermo Scientific™ MabPac™ RP column in in either stand-alone or integrated EASY-Spray design coupled to LC-MS.
<h3>Here we will focus on:</h3>
<ul>
<li>A novel column chemistry specifically designed in capillary format for the reproducible separation of therapeutic antibodies and their subunits</li>
<li>Bottom up applications to monitor protein attributes such as site occupancy, disulfate mapping at the peptide level</li>
</ul>
<h3>Key learning objectives:</h3>
<ul>
<li>Learn how to easily set-up the hyphenation between the new capillary MAbPac RP column and mass spectrometry for intact protein and bottom-up proteomics applications</li>
<li>Extend your capability in attaching nano and capillary columns to reliable and robust emitters</li>
</ul>
<h3>Who should attend:</h3>
<ul>
<li>Proteomics, biopharma and academic researchers interested in the characterization of intact proteins by top-down and bottom-up proteomics</li>
<li>Researchers whose sample volumes are small and who seek to use the capillary chromatography to increase the sensitivity and high throughput of mass spectrometry coupled workflows</li>
</ul>
<blockquote>
Presenter: Dr. Mike Baynham (Senior Product Manager, LC Columns, Thermo Fisher Scientific)
</blockquote>
<blockquote>
Mike Baynham is a Senior Product Manager and the Manager of the Product Management Team responsible for the Thermo Scientific LC column portfolio. Mike has worked for Thermo Fisher Scientific in Runcorn, UK since 2015. Mike has a doctorate in capillary separation techniques coupled to mass spectrometry from the University of Nottingham and has more than 25 years of experience of working with liquid chromatography.
</blockquote>
<blockquote>
Presenter: Dr. Ken Cook (EU Bio-Separations Expert, Thermo Fisher Scientific)
</blockquote>
<blockquote>
Dr. Ken Cook has 30 years of experience supporting liquid and ion chromatography applications with Dionex and then Thermo Fisher Scientific. Dr. Cook currently supports customers with bio-separations, focusing on biotherapeutics. Previously Dr. Cook was a lecturer in biochemistry at the University of Newcastle-Upon-Tyne, UK where he focused on protein biochemistry.
</blockquote>

Unsplash/National Cancer Institute: Workflows for robust and sensitive separation of mAbs, intact proteins at subunit and peptide level using capillary chromatography by LC-MS

Workflows for robust and sensitive separation of mAbs, intact proteins at subunit and peptide level using capillary chromatography by LC-MS