High-Throughput Bioanalytical LC/MS/MS Determination of Benzodiazepines in Human Urine:  1000 Samples per 12 Hours

Zweigenbaum, Jerry; Heinig, Katja; Steinborner, Simon T.; Wachs, and Timothy; Henion, Jack D.

doi:10.1021/ac9813540

Cited by 127 publications

(100 citation statements)

References 34 publications

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“…Therefore, analytical methods have to be developed to screen blood or urine samples for unknown chemicals or known drugs and their metabolites for compound identification to calculate ultimate exposure levels [2]. Over recent years, tandem LC-MS/MS has been extensively applied to quantify compounds with known structures using transitions for the sensitive multiple reaction monitoring (MRM) methods [3].…”

mentioning

confidence: 99%

Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer

Scholz

Dekant

Völkel

et al. 2005

J. Am. Soc. Mass Spectrom.

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A sensitive and specific liquid chromatography-mass spectrometry (LC-MS) method based on the combination of constant neutral loss scans (CNL) with product ion scans was developed on a linear ion trap. The method is applicable for the detection and identification of analytes with identical chemical substructures (such as conjugates of xenobiotics formed in biological systems) which give common CNLs. A specific CNL was observed for thioethers of N-acetyl-L-cysteine (mercapturic acids, MA) by LC-MS/MS. MS and HPLC parameters were optimized with 16 MAs available as reference compounds. All of these provided a CNL of 129 Da in the negative-ion mode. To assess sensitivity, a multiple reaction monitoring (MRM) mode with 251 theoretical transitions using the CNL of 129 Da combined with a product ion scan (IDA thMRM) was compared with CNL combined with a product ion scan (IDA CNL). An information-dependent acquisition (IDA) uses a survey scan such as MRM (multiple reaction monitoring) to generate "informations" and starting a second acquisition experiment such as a product ion scan using these "informations." Th-MRM means calculated transitions and not transitions generated from an available standard in the tuning mode. The product ion spectra provide additional information on the chemical structure of the unknown analytes. All MA standards were spiked in low concentrations to rat urines and were detected with both methods with LODs ranging from 60 pmol/mL to 1.63 nmol/mL with IDA thMRM. The expected product ion spectra were observed in urine. Application of this screening method to biological samples indicated the presence of a number of MAs in urine of unexposed rats, and resulted in the identification of 1,4-dihydroxynonene mercapturic acid as one of these MAs by negative and positive product ion spectra. These results show that the developed methods have a high potential to serve as both a prescreen to detect unknown MAs and to identify these analytes in complex matrix. (J Am Soc Mass Spectrom 2005, 16, 1976 -1984

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mentioning

confidence: 99%

Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer

Scholz

Dekant

Völkel

et al. 2005

J. Am. Soc. Mass Spectrom.

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“…Compared with other reports on analysis of several BZPs (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), in the screening method described in this study, the LLOQs for 19 BZPs or their major metabolites and 2 related compounds (zopliclone and zolpidem) are lower and seem to be appropriate for the detection and quantification of these compounds in urine samples from DFSA cases.…”

Section: Discussionmentioning

confidence: 58%

Liquid Chromatography–Tandem Mass Spectrometry for Detection of Low Concentrations of 21 Benzodiazepines, Metabolites, and Analogs in Urine: Method with Forensic Applications

et al. 2006

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“…The 96-well instruments can execute automated off-line extraction and sample clean-ups. Automated solid-phase extraction (SPE) [30][31][32][33][34][35][36][37], liquid/liquid extraction (LLE) [38][39][40][41][42][43][44], and protein precipitation (PP) [45,46] all can be performed in 96-well format. Both cartridge and disc in 96-well SPE formats have been successfully used.…”

Section: Sample Preparationmentioning

confidence: 99%

Critical Review of Development, Validation, and Transfer for High Throughput Bioanalytical LC-MS/MS Methods

Zhou¹,

Song²,

Tang³

et al. 2005

CPA

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Swift growth in the use of LC-MS/MS for the analysis of drugs in biological matrices has been compelled by the need for timely and high-quality data at many stages in drug discovery and development process: from high throughput screening of drug candidates and rapid data generation for pre-clinical studies to almost 'real-time' analysis of clinical samples. Prompt and rational method development, validation, and transfer play a pivotal role in achieving the goals of "faster, better, and cheaper" for pharmacokinetic studies since this could easily account for more than 50% of the time and labor resources for a moderate-sized project. Strategy for rational method development, validation and transfer has been largely kept as institutional knowledge but rarely appeared in literature. In this review article, strategies for developing and validating robust high throughput LC-MS/MS methods will be critically reviewed and discussed. Automated sample preparation, fast chromatography, minimization of matrix effects, and strategy of narrowing the gap between validation and incurred sample analysis are just a few topics covered in this review. Other interesting approaches for improving method efficiency and ruggedness such as direct injection SPE and liquid/liquid extracts as well as multiplexing of LC columns will also be discussed. Potential pitfalls during method development and validation are pointed out. At the end, the question "how fast is fast enough and how fast is too fast?" will be answered after considering all aspects of the method development and validation.

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High-Throughput Bioanalytical LC/MS/MS Determination of Benzodiazepines in Human Urine: 1000 Samples per 12 Hours

Cited by 127 publications

References 34 publications

Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer

Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer

Liquid Chromatography–Tandem Mass Spectrometry for Detection of Low Concentrations of 21 Benzodiazepines, Metabolites, and Analogs in Urine: Method with Forensic Applications

Critical Review of Development, Validation, and Transfer for High Throughput Bioanalytical LC-MS/MS Methods

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