Identification of lorazepam and sildenafil as examples for the application of LC/ionspray-MS and MS–MS with mass spectra library searching in forensic toxicology

Weinmann, Wolfgang; Lehmann, Natalie; Müller, Cláudia; Wiedemann, Alexander; Svoboda, Michal

doi:10.1016/s0379-0738(00)00256-5

Cited by 30 publications

(22 citation statements)

References 7 publications

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“…MS/MS libraries with CID-spectra of the quasimolecular ions can be very useful for this purpose. Therefore, MS/MS libraries of drugs have been developed using triple-quadrupole instruments [9,10]. Besides these MS/MS libraries, a procedure using MS/MS and MS 3 spectra libraries with ion-trap detectors using wideband excitation has been developed for general-unknown screening [11][12][13][14], including the use of data dependent experiments (DDE).…”

Section: Introductionmentioning

confidence: 99%

MS/MS-libraries with triple quadrupole-tandem mass spectrometers for drug identification and drug screening

Weinmann¹,

Gergov²,

Goerner³

2000

Analusis

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Two MS/MS libraries of drugs created by electrospray ionisation (ESI) and collision-induced dissociation (CID) of the quasimolecular ionshave been developed with triple-quadrupole ionspray mass spectrometers. For both libraries three and four different collision energies were used, respectively, to obtain a variety of CID spectra, which were all included separately into the MS/MS libraries. The MS/MS product ion spectra of more than 400 drugs were acquired in positive or negative mode in two laboratories independently. Recently, one of these MS/MS libraries was applied successfully for the identification of drug metabolites and the other has been used for qualitative analysis of drugs in urine samples with data dependent experiments (DDE). In this work, the reproducibility of CID spectra has been tested with three instruments (including two different instruments) in three laboratories. For comparison of CID-spectra, library searching with a combination of the two libraries was performed and fit values were compared. With regard to library fit values CID-spectra were found to be highly reproducible between the instruments, when similar CID gas pressure and collision energy were applied. In addition, the long-time reproducibility of CID over 30 months with the API 365 was demonstrated. Furthermore, comparisons of in-source CID and CID by MS/MS was given. It can be concluded, that both MS/MS libraries created with APIs 365 can be used with both types of triple-quadrupole instruments from Sciex (API 365 and 2000) for drug identification. Two applications of these MS/MS spectra libraries in combination with data dependent experiments are summarised.

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Section: Introductionmentioning

confidence: 99%

MS/MS-libraries with triple quadrupole-tandem mass spectrometers for drug identification and drug screening

Weinmann¹,

Gergov²,

Goerner³

2000

Analusis

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“…HPLC 5) and LC-MS 6) techniques have been reported to date as analytical methods for the determination of SDF and/or its metabolites in biological samples. However, no GC-MS method for SDF has been reported so far, probably because in addition to their thermolability, it is difficult to derivatize SDF analogies with standard silylation reagents.…”

mentioning

confidence: 99%

Hair Analysis for Pharmaceutical Drugs. II. Effective Extraction and Determination of Sildenafil (Viagra) and Its N-Desmethyl Metabolite in Rat and Human Hair by GC-MS.

Saisho¹,

Scott²,

Morimoto

et al. 2001

Biological & Pharmaceutical Bulletin

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“…A number of papers have been published discussing the MS detection of LOR in HPLC [20][21][22][23][24] or CE [31,32]. In these approaches, LOR was detected as a positive ion.…”

Section: Previous Work and Analysis Of Lor And Lor-3o-glucuronide By mentioning

confidence: 99%

“…The confirmation of the presence of LOR and structurally related compounds in body fluids is performed by GC with electron capture [11] or MS detection [16,18], by HPLC with UV [19] or MS [20][21][22][23][24] detection, and by MEKC with UV detection [13,25]. Much less has been published concerning the analysis of LOR-3O-glucuronide.…”

Section: Introductionmentioning

confidence: 99%

“…Much less has been published concerning the analysis of LOR-3O-glucuronide. Reported methods include TLC [1], HPLC-MS [20], GC [11], and chemical ionization MS after derivatization with trimethylsilane [26]. Our laboratory is specializing in the elucidation of drug metabolism using CE with UV and MS detection [27], including the stereoselectivity of drug metabolism employing enantioselective CE methods that were found to be highly suitable for analysis of drug enantiomers in body fluids and tissues [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of lorazepam and its 3O‐glucuronide in human urine by capillary electrophoresis: Evidence for the formation of two distinct diastereoisomeric glucuronides

Baldacci

Thormann²

2006

J of Separation Science

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Lorazepam (LOR) is a 3-hydroxy-1,4-benzodiazepine that is chiral and undergoes enantiomerization at room temperature. In humans, about 75% of the administered dose of LOR is excreted in the urine as its 30-glucuronide. CE-MS with negative ESI was used to confirm the presence of LOR-30-glucuronide in urines that stemmed from a healthy individual who ingested 1 or 2 mg LOR, whereas free LOR could be detected in extracts prepared from enzymatically hydrolyzed urines. As the 30-glucuronidation reaction occurs at the chiral center of the molecule, two diastereoisomers can theoretically be formed, molecules that can no longer interconvert. The stereoselective formation of LOR glucuronides in humans and in vitro was investigated. MEKC analysis of extracts of the nonhydrolyzed urines suggested the presence of the two different LOR glucuronides in the urine. The formation of the same two diastereoisomers was also observed in vitro employing incubations of LOR with human liver microsomes in the presence of uridine 5'-diphospho-glucuronic acid as coenzyme. The absence of other coenzymes excluded the formation of phase I or other phase II metabolites of LOR. Both results revealed a stereoselectivity, one diastereoisomer being formed in a higher amount than the other. After enzymatic hydrolysis using beta-glucuronidase, these peaks could not be detected any more. Instead, LOR was monitored. Analysis of the extracts prepared from enzymatically hydrolyzed urines by MEKC in the presence of 2-hydroxypropyl-beta-CD revealed the enantiomerization process of LOR (observation of two peaks of equal magnitude connected with a plateau zone). The data presented provide for the first time the evidence of the stereoselectivity of the LOR glucuronidation in humans.

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Identification of lorazepam and sildenafil as examples for the application of LC/ionspray-MS and MS–MS with mass spectra library searching in forensic toxicology

Cited by 30 publications

References 7 publications

MS/MS-libraries with triple quadrupole-tandem mass spectrometers for drug identification and drug screening

MS/MS-libraries with triple quadrupole-tandem mass spectrometers for drug identification and drug screening

Hair Analysis for Pharmaceutical Drugs. II. Effective Extraction and Determination of Sildenafil (Viagra) and Its N-Desmethyl Metabolite in Rat and Human Hair by GC-MS.

Analysis of lorazepam and its 3O‐glucuronide in human urine by capillary electrophoresis: Evidence for the formation of two distinct diastereoisomeric glucuronides

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