Displaying publications 61 - 80 of 322 in total

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  1. Separation of Antioxidant-Rich Alternanthera Sessilis Red Extracts by Sephadex LH-20 and Identification of Polyphenols Using HPLC-QToF-MS/MS
    Hwong CS, Leong KH, Aziz AA, Kong KW
    Chem Biodivers, 2023 Jul;20(7):e202300215.
    PMID: 37278124 DOI: 10.1002/cbdv.202300215
    This study aimed to fractionate Alternanthera sessilis Red (ASR) crude extracts and determine their antioxidant activities as well as the related active components in the whole plant. ASR was extracted with water and ethanol, and further separated using a Sephadex LH-20 column. Following the assessments of the polyphenolic contents and antioxidant activities of crude extracts (H2 OASR and EtOHASR ) and fractions, a HPLC-QToF analysis was performed on the crude extracts and selected fractions (H2 OASR FII and EtOHASR FII). Three water fractions (H2 OASR FI, FII and FIII) and four ethanolic fractions (EtOHASR FI, FII, FIII and FIV) were derived from their crude extracts, respectively. EtOHASR FII exhibited the greatest total phenolic content (120.41 mg GAE/g fraction), total flavonoid content (223.07 mg RE/g fraction), and antioxidant activities (DPPH IC50 =159.43 μg/mL; FRAP=1.93 mmol Fe2+ /g fraction; TEAC=0.90 mmol TE/g fraction). Correlation analysis showed significant (p<0.01) positive correlations between both TPC (r=0.748-0.970) and TFC (r=0.686-0.949) with antioxidant activities in the crude extracts and fractions. Flavonoids were the major compounds in the four selected samples tentatively identified using HPLC-QToF-MS/MS, with the highest number of 30 polyphenol compounds detected in the most active fraction, EtOHASR FII.
    Matched MeSH terms: Tandem Mass Spectrometry
  2. LC-MS profiling-based non-targeted secondary metabolite screening for deciphering cosmeceutical potential of Malaysian algae
    Lim MW, Yow YY, Gew LT
    J Cosmet Dermatol, 2023 Oct;22(10):2810-2815.
    PMID: 37313630 DOI: 10.1111/jocd.15794
    BACKGROUND: Application of natural resources from the marine environment in the cosmeceutical industry is gaining great attention.

    AIM: This study pursues to discover the cosmeceutical potential of two Malaysian algae, Sargassum sp. and Kappaphycus sp. by determining their antioxidant capacity and assessing the presence of their secondary metabolites with cosmeceutical potential using non-targeted metabolite profiling.

    METHODS: Metabolite profiling using Quadrupole Time-of-Flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) in the Electrospray Ionization (ESI) mode resulted in 110 putative metabolites in Sargassum sp. and 47 putative metabolites in Kappaphycus sp. and were grouped according to their functions. To the best of our knowledge, the bioactive compounds of both algae have not been studied in any great detail. This is the first report to explore their cosmeceutical potential.

    RESULTS: Six antioxidants were detected in Sargassum sp., including fucoxanthin, (3S, 4R, 3'R)-4-Hydroxyalloxanthin, enzacamene N-stearoyl valine, 2-hydroxy-hexadecanoic acid, and metalloporphyrins. Meanwhile, three antioxidants detected in Kappahycus sp., namely Tanacetol A, 2-fluoro palmitic acid and idebenone metabolites. Three antioxidants are found in both algae species, namely, 3-tert-Butyl-5-methylcatechol, (-)-isoamijiol, and (6S)-dehydrovomifoliol. Anti-inflammatory metabolites such as 5(R)-HETE, protoverine, phytosphingosine, 4,5-Leukotriene-A4, and 5Z-octadecenoic acid were also found in both species. Sargassum sp. possesses higher antioxidant capacity as compared to Kappahycus sp. which may be linked to its number of antioxidant compounds found through LC-MS.

    CONCLUSIONS: Hence, our results conclude that Malaysian Sargassum sp. and Kappaphycus sp. are potential natural cosmeceutical ingredients as we aim to produce algae cosmeceutical products using native algae.

    Matched MeSH terms: Tandem Mass Spectrometry
  3. Dietary exposure to acrylamide among the Malaysian adult population
    Nur Hidayah J, Abdul Razis AF, Jambari NN, Chai LC, You L, Sanny M
    Food Chem Toxicol, 2024 Mar;185:114502.
    PMID: 38346572 DOI: 10.1016/j.fct.2024.114502
    This study aimed to estimate the Malaysian adult population's current dietary exposure and margin of exposure (MOE) to the carcinogenic processing contaminant, acrylamide. A total of 448 samples from 11 types of processed foods were collected randomly throughout Malaysia in the year 2015 and 2016. Acrylamide was analysed in samples using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) with a limit of detection (LOD) of 10 μg/kg and a limit of quantification (LOQ) of 25 μg/kg. The highest average level of acrylamide (772 ± 752 μg/kg) was found in potato crisps, followed by French fries (415 ± 914 μg/kg) and biscuits (245 ± 195 μg/kg). The total acrylamide exposure for the adult Malaysian was 0.229 and 1.77 μg/kg body weight per day for average and high consumers, respectively. The MOE were 741 and 1875 for the average consumer based on cancer and non-cancer effects of acrylamide, respectively. Meanwhile, for high consumers, the MOE is 96 for cancer and 243 for non-cancer effects. These findings indicate potential carcinogenic risks from acrylamide exposure among Malaysian adults, especially in Malay and other Bumiputra groups compared to Chinese, Indian, and other ethnic groups, while non-cancer effects appeared less concerning.
    Matched MeSH terms: Tandem Mass Spectrometry
  4. Fulltext Physicochemical and antioxidant properties of Apis cerana honey from Lombok and Bali Islands
    Huyop F, Ullah S, Abdul Wahab R, Huda N, Sujana IGA, Saloko S, et al.
    PLoS One, 2024;19(4):e0301213.
    PMID: 38578814 DOI: 10.1371/journal.pone.0301213
    Limited honey production worldwide leads to higher market prices, thus making it prone to adulteration. Therefore, regular physicochemical analysis is imperative for ensuring authenticity and safety. This study describes the physicochemical and antioxidant properties of Apis cerana honey sourced from the islands of Lombok and Bali, showing their unique regional traits. A comparative analysis was conducted on honey samples from Lombok and Bali as well as honey variety from Malaysia. Moisture content was found slightly above 20% in raw honey samples from Lombok and Bali, adhering to the national standard (SNI 8664:2018) of not exceeding 22%. Both honey types displayed pH values within the acceptable range (3.40-6.10), ensuring favorable conditions for long-term storage. However, Lombok honey exhibited higher free acidity (78.5±2.14 meq/kg) than Bali honey (76.0±1.14 meq/kg), surpassing Codex Alimentarius recommendations (≤50 meq/kg). The ash content, reflective of inorganic mineral composition, was notably lower in Lombok (0.21±0.02 g/100) and Bali honey (0.14±0.01 g/100) compared to Tualang honey (1.3±0.02 g/100). Electric conductivity, indicative of mineral content, revealed Lombok and Bali honey with lower but comparable values than Tualang honey. Hydroxymethylfurfural (HMF) concentrations in Lombok (14.4±0.11 mg/kg) and Bali (17.6±0.25 mg/kg) were slightly elevated compared to Tualang honey (6.4±0.11 mg/kg), suggesting potential processing-related changes. Sugar analysis revealed Lombok honey with the highest sucrose content (2.39±0.01g/100g) and Bali honey with the highest total sugar content (75.21±0.11 g/100g). Both honeys exhibited lower glucose than fructose content, aligning with Codex Alimentarius guidelines. The phenolic content, flavonoids, and antioxidant activity were significantly higher in Lombok and Bali honey compared to Tualang honey, suggesting potential health benefits. Further analysis by LC-MS/MS-QTOF targeted analysis identified various flavonoids/flavanols and polyphenolic/phenolic acid compounds in Lombok and Bali honey. The study marks the importance of characterizing the unique composition of honey from different regions, ensuring quality and authenticity in the honey industry.
    Matched MeSH terms: Tandem Mass Spectrometry
  5. Development and validation of a selective, sensitive and stability indicating UPLC-MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance
    A VBR, Yusop Z, Jaafar J, Aris AB, Majid ZA, Umar K, et al.
    J Pharm Biomed Anal, 2016 Sep 05;128:141-148.
    PMID: 27262107 DOI: 10.1016/j.jpba.2016.05.026
    In this study a sensitive and selective gradient reverse phase UPLC-MS/MS method was developed for the simultaneous determination of six process related impurities viz., Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V and Imp-VI in darunavir. The chromatographic separation was performed on Acquity UPLC BEH C18 (50 mm×2.1mm, 1.7μm) column using gradient elution of acetonitrile-methanol (80:20, v/v) and 5.0mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously using multiple reaction monitoring (MRM) for the quantification of all six impurities in darunavir. The developed method was fully validated following ICH guidelines with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, robustness and sample solution stability. The method was able to quantitate Imp-I, Imp-IV, Imp-V at 0.3ppm and Imp-II, Imp-III, and Imp-VI at 0.2ppm with respect to 5.0mg/mL of darunavir. The calibration curves showed good linearity over the concentration range of LOQ to 250% for all six impurities. The correlation coefficient obtained was >0.9989 in all the cases. The accuracy of the method lies between 89.90% and 104.60% for all six impurities. Finally, the method has been successfully applied for three formulation batches of darunavir to determine the above mentioned impurities, however no impurity was found beyond the LOQ. This method is a good quality control tool for the trace level quantification of six process related impurities in darunavir during its synthesis.
    Matched MeSH terms: Tandem Mass Spectrometry/methods
  6. Fulltext Rapid and simultaneous quantification of levetiracetam and its carboxylic metabolite in human plasma by liquid chromatography tandem mass spectrometry
    Yeap LL, Lo YL
    PLoS One, 2014;9(11):e111544.
    PMID: 25375249 DOI: 10.1371/journal.pone.0111544
    A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV) and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.450 mL acetonitrile (ACN) containing 1 µg/mL of internal standard (IS, diphenhydramine), then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution was injected into an Agilent Zorbax SB-C18 (2.1 mm×100 mm, 3.5 µm) column with an isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and ACN (40:60 v/v). Detection was performed using an AB Sciex API 3000 triple quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of quantification (LLOQ) for both LEV and UCB L057 was validated at 0.5 µg/mL, while their lower limit of detection (LOD) was 0.25 µg/mL. The calibration curves were linear between 0.5 and 100 µg/mL for both analytes. The inaccuracy and imprecision of both intra-assay and inter-assay were less than 10%. Matrix effects were consistent between sources of plasma and the recoveries of all compounds were between 100% and 110%. Stability was established under various storage and processing conditions. The carryovers from both LEV and UCB L057 were less than 6% of the LLOQ and 0.13% of the IS. This assay method has been successfully applied to a population pharmacokinetic study of LEV in patients with epilepsy.
    Matched MeSH terms: Tandem Mass Spectrometry*
  7. Fulltext Tandem mass spectrometry detection of quorum sensing activity in multidrug resistant clinical isolate Acinetobacter baumannii
    Chan KG, Cheng HJ, Chen JW, Yin WF, Ngeow YF
    ScientificWorldJournal, 2014;2014:891041.
    PMID: 25101326 DOI: 10.1155/2014/891041
    Many Proteobacteria communicate via production followed by response of quorum sensing molecules, namely, N-acyl homoserine lactones (AHLs). These molecules consist of a lactone moiety with N-acyl side chain with various chain lengths and degrees of saturation at C-3 position. AHL-dependent QS is often associated with regulation of diverse bacterial phenotypes including the expression of virulence factors. With the use of biosensor and high resolution liquid chromatography tandem mass spectrometry, the AHL production of clinical isolate A. baumannii 4KT was studied. Production of short chain AHL, namely, N-hexanoyl-homoserine lactone (C6-HSL) and N-octanoyl-homoserine lactone (C8-HSL), was detected.
    Matched MeSH terms: Tandem Mass Spectrometry/methods*
  8. Fulltext Detection of quorum sensing activity in the multidrug-resistant clinical isolate Pseudomonas aeruginosa strain GB11
    Cheng HJ, Ee R, Cheong YM, Tan WS, Yin WF, Chan KG
    Sensors (Basel), 2014;14(7):12511-22.
    PMID: 25019635 DOI: 10.3390/s140712511
    A multidrug-resistant clinical bacteria strain GB11 was isolated from a wound swab on the leg of a patient. Identity of stain GB11 as Pseudomonas aeruginosa was validated by using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Detection of the production of signaling molecules, N-acylhomoserine lactones (AHLs), was conducted using three different bacterial biosensors. A total of four different AHLs were found to be produced by strain GB11, namely N-butyryl homoserine lactone (C4-HSL), N-hexanoylhomoserine lactone (C6-HSL), N-octanoyl homoserine lactone (C8-HSL) and N-3-oxo-dodecanoylhomoserine lactone (3-oxo-C12-HSL) using high resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). Of these detected AHLs, 3-oxo-C12-HSL was found to be the most abundant AHL produced by P. aeruginosa GB11.
    Matched MeSH terms: Tandem Mass Spectrometry/methods
  9. Micro-solid phase extraction with liquid chromatography-tandem mass spectrometry for the determination of aflatoxins in coffee and malt beverage
    Khayoon WS, Saad B, Salleh B, Manaf NH, Latiff AA
    Food Chem, 2014 Mar 15;147:287-94.
    PMID: 24206720 DOI: 10.1016/j.foodchem.2013.09.049
    A single step extraction-cleanup procedure using porous membrane-protected micro-solid phase extraction (μ-SPE) in conjunction with liquid chromatography-tandem mass spectrometry for the extraction and determination of aflatoxins (AFs) B1, B2, G1 and G2 from food was successfully developed. After the extraction, AFs were desorbed from the μ-SPE device by ultrasonication using acetonitrile. The optimum extraction conditions were: sorbent material, C8; sorbent mass, 20mg; extraction time, 90 min; stirring speed, 1,000 rpm; sample volume, 10 mL; desorption solvent, acetonitrile; solvent volume, 350 μL and ultrasonication period, 25 min without salt addition. Under the optimum conditions, enrichment factor of 11, 9, 9 and 10 for AFG2, AFG1, AFB2 and AFB1, respectively were achieved. Good linearity and correlation coefficient was obtained over the concentration range of 0.4-50 ng g(-1) (r(2) 0.9988-0.9999). Good recoveries for AFs ranging from 86.0-109% were obtained. The method was applied to 40 samples involving malt beverage (19) and canned coffee (21). No AFs were detected in the selected samples.
    Matched MeSH terms: Tandem Mass Spectrometry/methods*
  10. Development and validation of a rapid ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of darunavir, ritonavir, and tenofovir in human plasma: Application to human pharmacokinetics
    Reddy AV, Jaafar J, Aris AB, Majid ZA, Umar K, Talib J, et al.
    J Sep Sci, 2015 Aug;38(15):2580-7.
    PMID: 25989063 DOI: 10.1002/jssc.201500250
    A sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of darunavir, ritonavir and tenofovir in human plasma. Sample preparation involved a simple liquid-liquid extraction using 200 μL of human plasma extracted with methyl tert-butyl ether for three analytes and internal standard. The separation was accomplished on an Acquity UPLC BEH C18 (50 mm x 2.1 mm, 1.7 μm) analytical column using gradient elution of acetonitrile/methanol (80:20, v/v) and 5.0 mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4 mL/min. The linearity of the method ranged between 20.0 and 12 000 ng/mL for darunavir, 2.0 and 2280 ng/mL for ritonavir, and 14.0 and 1600 ng/mL for tenofovir using 200 μL of plasma. The method was completely validated for its selectivity, sensitivity, linearity, precision and accuracy, recovery, matrix effect, stability, and dilution integrity. The extraction recoveries were consistent and ranged between 79.91 and 90.04% for all three analytes and internal standard. The method exhibited good intra-day and inter-day precision between 1.78 and 6.27%. Finally the method was successfully applied for human pharmacokinetic study in eight healthy male volunteers after the oral administration of 600 mg darunavir along with 100 mg ritonavir and 100 mg tenofovir as boosters.
    Matched MeSH terms: Tandem Mass Spectrometry/methods*
  11. Application of a Mass Spectrometric Approach to Detect the Presence of Fatty Acid Biosynthetic Phosphopeptides
    Lau BY, Clerens S, Morton JD, Dyer JM, Deb-Choudhury S, Ramli US
    Protein J, 2016 Apr;35(2):163-70.
    PMID: 26993480 DOI: 10.1007/s10930-016-9655-0
    The details of plant lipid metabolism are relatively well known but the regulation of fatty acid production at the protein level is still not understood. Hence this study explores the importance of phosphorylation as a mechanism to control the activity of fatty acid biosynthetic enzymes using low and high oleic acid mesocarps of oil palm fruit (Elaeis guineensis variety of Tenera). Adaptation of neutral loss-triggered tandem mass spectrometry and selected reaction monitoring to detect the neutral loss of phosphoric acid successfully found several phosphoamino acid-containing peptides. These peptides corresponded to the peptides from acetyl-CoA carboxylase and 3-enoyl-acyl carrier protein reductase as identified by their precursor ion masses. These findings suggest that these enzymes were phosphorylated at 20th week after anthesis. Phosphorylation could have reduce their activities towards the end of fatty acid biosynthesis at ripening stage. Implication of phosphorylation in the regulation of fatty acid biosynthesis at protein level has never been reported.
    Matched MeSH terms: Tandem Mass Spectrometry/methods*
  12. Fulltext Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra-performance liquid chromatography-tandem mass spectrometry
    Sharma A, Kamble SH, León F, Chear NJ, King TI, Berthold EC, et al.
    Drug Test Anal, 2019 Aug;11(8):1162-1171.
    PMID: 30997725 DOI: 10.1002/dta.2604
    Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self-treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10mM, pH 3.5). The developed method was linear over a concentration range of 1-200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 minutes. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid-rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7%-38.7% w/w), paynantheine (0.3%-12.8% w/w), speciociliatine (0.4%-12.3% w/w), and speciogynine (0.1%-5.3% w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine) were also quantified (0.01%-2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.
    Matched MeSH terms: Tandem Mass Spectrometry/methods
  13. Fulltext Trace Level Detection of Bisphenol A Analogues and Parabens by LC-MS/MS in Human Plasma from Malaysians
    Wiraagni IA, Mohd MA, Rashid RA, Haron DEBM
    Biomed Res Int, 2020;2020:2581287.
    PMID: 32420332 DOI: 10.1155/2020/2581287
    In this study, a novel LC-MS/MS method was designed using a simple extraction procedure that was scientifically developed to capture the most relevant bisphenol A (BPA) analogues (BPB, BPF, BPS, and BPAF) and parabens (propylparaben, ethylparaben, butylparaben, and methylparaben) in human plasma. The LC-MS/MS method was validated using US FDA guidelines, and all validation requirements were satisfactory. This is the method that allows for the detection of plasma bisphenols and parabens in one run and is also the fastest BPA analogue and paraben detection technique for human plasma. The method was used to analyze samples from 150 healthy volunteers from Malaysia who enrolled in the study. No BPB was detected in any of the volunteers; however, 99.3% were positive for BPF. Only 24% and 10.7% of volunteers were positive for BPAF and BPS, respectively. A high percentage of volunteers were negative for propylparaben, ethylparaben, butylparaben, and methylparaben (56%, 68%, 86.7%, and 83.3%, respectively). These results suggest that persons in Malaysia are exposed to different BPA analogues and parabens, from both the daily use of products (cosmetic and plastic products) and the environment.
    Matched MeSH terms: Tandem Mass Spectrometry*
  14. Fulltext Dispersive Liquid-Liquid Microextraction (DLLME) and LC-MS/MS Analysis for Multi-Mycotoxin in Rice Bran: Method Development, Optimization and Validation
    Salim SA, Sukor R, Ismail MN, Selamat J
    Toxins (Basel), 2021 04 15;13(4).
    PMID: 33920815 DOI: 10.3390/toxins13040280
    Rice bran, a by-product of the rice milling process, has emerged as a functional food and being used in formulation of healthy food and drinks. However, rice bran is often contaminated with numerous mycotoxins. In this study, a method to simultaneous detection of aflatoxins (AFB1, AFB2, AFG1, and AFG2), ochratoxin A (OTA), deoxynivalenol (DON), fumonisins (FB1 and FB2), sterigmatocystin (STG), T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and zearalenone (ZEA) in rice bran was developed, optimized and validated using dispersive liquid-liquid microextraction (DLLME) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In DLLME, using a solvent mixture of methanol/water (80:20, v/v) as the dispersive solvent and chloroform as the extraction solvent with the addition of 5% salt improved the extraction recoveries (63-120%). The developed method was further optimized using the response surface methodology (RSM) combined with Box-Behnken Design (BBD). Under the optimized experimental conditions, good linearity was obtained with a correlation coefficient (r2) ≥ 0.990 and a limit of detection (LOD) between 0.5 to 50 ng g-1. The recoveries ranged from 70.2% to 99.4% with an RSD below 1.28%. The proposed method was successfully applied to analyze multi-mycotoxin in 24 rice bran samples.
    Matched MeSH terms: Tandem Mass Spectrometry*
  15. Fulltext Prediction of Fluoroquinolone Susceptibility Directly from Whole-Genome Sequence Data by Using Liquid Chromatography-Tandem Mass Spectrometry To Identify Mutant Genotypes
    Wan Nur Ismah WAK, Takebayashi Y, Findlay J, Heesom KJ, Jiménez-Castellanos JC, Zhang J, et al.
    Antimicrob Agents Chemother, 2018 03;62(3).
    PMID: 29263066 DOI: 10.1128/AAC.01814-17
    Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and in vitro mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using Klebsiella pneumoniae as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in K. pneumoniae clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility.
    Matched MeSH terms: Tandem Mass Spectrometry/methods*
  16. QbD-Driven Development and Validation of Liquid Chromatography Tandem Mass Spectrometric Method for the Quantitation of Sildenafil in Human Plasma
    Hasnain MS, Ansari SA, Rao S, Tabish M, Singh M, Abdullah MS, et al.
    J Chromatogr Sci, 2017 Jul 01;55(6):587-594.
    PMID: 28335023 DOI: 10.1093/chromsci/bmx010
    The present work was employing the Quality by Design approach for the development and validation of a LC-MS-MS method to support the clinical advancement in determination of sildenafil in human plasma using lorazepam as an internal standard. Sample preparation involved solid phase extraction and calibration range observed between 3 and 1,700 ng/mL. The method was systematically optimized by employing Box-Behnken design and used mobile phase flow rate, pH and composition of mobile phase as the critical factors, and assessing the design for retention time and peak area as the responses. A substantial decrease in the variability associated with the method variables was shown in optimization studies and confirmed enhanced method robustness. The present studies revealed that developed method achieves all the regulatory requirements for linearity, accuracy, precision, selectivity, sensitivity and stability for the determination of sildenafil in human plasma. There was not any significant change in the stability of the drug shown by stability studies, performed in human plasma through freeze-thaw cycles, bench-top stability, short-term stability, long-term stability and auto sampler stability. In short, this method shows satisfactory results for the analysis of sildenafil in human plasma and possesses high degree of utility in pharmacokinetic and bioequivalence studies.
    Matched MeSH terms: Tandem Mass Spectrometry/methods*
  17. Risk assessment of pharmaceutically active compounds (PhACs) in the Klang River estuary, Malaysia
    Omar TFT, Aris AZ, Yusoff FM, Mustafa S
    Environ Geochem Health, 2019 Feb;41(1):211-223.
    PMID: 30051257 DOI: 10.1007/s10653-018-0157-1
    The concentration profile, distribution and risk assessment of pharmaceutically active compounds (PhACs) in the coastal surface water from the Klang River estuary were measured. Surface coastal water samples were extracted using offline solid phase, applying polymeric C18 cartridges as extraction sorbent and measuring with liquid chromatography mass spectrometry-mass spectrometry (LC MS-MS) technique. Extraction method was optimized for its recovery, sensitivity and linearity. Excellent recoveries were obtained from the optimized method with percentage of recoveries ranging from 73 to 126%. The optimized analytical method achieved good sensitivity with limit of detection ranging from 0.05 to 0.15 ng L-1, while linearity of targeted compounds in the LC MS-MS system was more than 0.990. The results showed that amoxicillin has the highest concentration (102.31 ng L-1) followed by diclofenac (10.80 ng L-1) and primidone (7.74 ng L-1). The percentage of contribution (% of total concentration) for the targeted PhACs is in the following order; amoxicillin (92.90%) > diclofenac (3.95%) > primidone (1.23%) > dexamethasone (0.75%) > testosterone (0.70%) > sulfamethoxazole (0.33%) > progesterone (0.14%). Environmental risk assessment calculated based on deterministic approach (the RQ method), showed no present risk from the presence of PhACs in the coastal water of Klang River estuary. Nonetheless, this baseline assessment can be used for better understanding on PhACs pollution profile and distribution in the tropical coastal and estuarine ecosystem as well as for future comparative studies.
    Matched MeSH terms: Tandem Mass Spectrometry/methods
  18. UHPLC-MS phytochemical profiling, biological propensities and in-silico studies of Alhagi maurorum roots: a medicinal herb with multifunctional properties
    Saleem H, Sarfraz M, Khan KM, Anwar MA, Zengin G, Ahmad I, et al.
    Drug Dev Ind Pharm, 2020 May;46(5):861-868.
    PMID: 32352878 DOI: 10.1080/03639045.2020.1762199
    The biological, chemical, and in silico properties of methanol and dichloromethane (DCM) extracts of Alhagi maurorum roots with respect to the antioxidant, enzyme inhibition, and phytochemical composition were evaluated. Total bioactive contents were determined spectrophotometrically, and the individual secondary metabolites composition was assessed via ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) analysis. Antioxidant capacities were evaluated using a panoply of assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging, ferric reducing antioxidant power (FRAP), cupric reducing antioxidant power (CUPRAC), phosphomolybdenum total antioxidant capacity (TAC), and metal chelating activity (MCA)). The enzyme inhibition potential was studied against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, α-glucosidase, tyrosinase, urease and lipoxygenase (LOX) enzymes. The methanol extract was found to contain higher total phenolic (105.91 mg GAE/g extract) and flavonoid (2.27 mg RE/g extract) contents which can be correlated to its more substantial antioxidant potential as well as AChE, BChE, tyrosinase and α-glucosidase inhibition. However, the DCM extract was the most effective against α-amylase (1.86 mmol ACAE/g extract) enzyme inhibition. The UHPLC-MS analysis of methanol extract identified the tentative presence of a total of 18 secondary metabolites, including flavonoids, saponins, phenolic and terpenoid derivatives. Three compounds named emmotin A, luteolin 5,3'-dimethyl ether, and preferrugone were further investigated for their in silico molecular docking studies against the tested enzymes. The selected compounds were found to have higher binding interaction with AChE followed by BChE, α-glucosidase, α-amylase, and tyrosinase. The results of the present study have demonstrated A. mauroram to be considered as a lead source of natural antioxidant and enzyme inhibitor compounds.
    Matched MeSH terms: Tandem Mass Spectrometry/methods
  19. Development of LC-MS/MS method and application to bioequivalence study of a light sensitive drug montelukast
    Wong EYL, Loh GOK, Tan YTF, Peh KK
    Drug Dev Ind Pharm, 2021 Feb;47(2):197-206.
    PMID: 33300818 DOI: 10.1080/03639045.2020.1862177
    OBJECTIVE: The aim of the study was to develop a simple, highthroughput and sensitive LC-MS/MS method and apply to a bioequivalence study of montelukast, a light sensitive drug.

    METHOD: The effects of organic modifiers in mobile phase, protein precipitation agent to plasma sample ratio, and light on montelukast stability in unprocessed and processed human plasma, were evaluated. Validation was conducted in accordance with European Medicines Agency Guideline on bioanalytical method validation.

    RESULTS: No interference peak was observed when acetonitrile was used as an organic modifier. Acetonitrile to plasma ratio of 4:1 produced clean plasma sample. Approximately 3 % of cis isomer was detected in unprocessed plasma samples while 21 % of cis isomer was detected in processed plasma samples after exposing to fluorescent light for 24h. The standard calibration curve was linear over 3.00-1200.00 ng/mL. All method validation parameters were within the acceptance criteria.

    CONCLUSION: The validated method was successfully applied to a bioequivalence study of two montelukast formulations involving 24 healthy Malaysian volunteers. The light stability of a light sensitive drug in unprocessed and processed human plasma samples should be studied prior to pharmacokinetic/bioequivalence studies. Measures could then be taken to protect the analyte in human plasma from light degradation.

    Matched MeSH terms: Tandem Mass Spectrometry*
  20. Evaluation of extraction methods for the identification of proteins from date palm (Phoenix dactylifera L.) seed and flesh
    Lee HX, Ahmad F, Saad B, Ismail MN
    Prep Biochem Biotechnol, 2017 Nov 26;47(10):998-1007.
    PMID: 28857669 DOI: 10.1080/10826068.2017.1365250
    Date fruits are well known to be very nutritious. Nevertheless, the protein contents of the fruit, particularly the seed and flesh, are still understudied, largely due to their difficult physical characteristics. This study was conducted to compare three different protein extraction methods which were the trichloroacetic acid (TCA)-acetone (TCA-A), phenol (Phe), and TCA-acetone-phenol (TCA-A-Phe), and to perform proteomic analysis on date palm seed and flesh. Phe extraction method showed the highest protein yields for both seed (8.26 mg/g) and flesh (1.57 mg/g). Through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Phe, and TCA-A-Phe extraction methods were shown to be efficient in removing interfering compounds and gave well-resolved bands over a wide range of molecular weights. Following liquid chromatography-tandem mass spectrometry analysis, about 50-64% of extracted proteins were identified with known functions including those involved in glycolysis, Krebs cycle, defense, and storage. Phe protein extraction method was proven to be the optimal method for date flesh and seed.
    Matched MeSH terms: Tandem Mass Spectrometry/methods
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