title: Ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction for the determination of 4 designer benzodiazepines in urine samples by gas chromatography-triple quadrupole mass spectrometry.
abstract: A novel microextraction technique based on ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) had been applied for the determination of 4 designer benzodiazepines (phenazepam, diclazepam, flubromazepam and etizolam) in urine samples by gas chromatography- triple quadrupole mass spectrometry (GC-QQQ-MS). Ethyl acetate (168μL) was added into the urine samples after adjusting pH to 11.3. The samples were sonicated in an ultrasonic bath for 5.5min to form a cloudy suspension. After centrifugation at 10000rpm for 3min, the supernatant extractant was withdrawn and injected into the GC-QQQ-MS for analysis. Parameters affecting the extraction efficiency have been investigated and optimized by means of single factor experiment and response surface methodology (Box-Behnken design). Under the optimum extraction conditions, a recovery of 73.8-85.5% were obtained for all analytes. The analytical method was linear for all analytes in the range from 0.003 to 10μg/mL with the correlation coefficient ranging from 0.9978 to 0.9990. The LODs were estimated to be 1-3ng/mL. The accuracy (expressed as mean relative error MRE) was within ±5.8% and the precision (expressed as relative standard error RSD) was less than 5.9%. UA-LDS-DLLME technique has the advantages of shorter extraction time and is suitable for simultaneous pretreatment of samples in batches. The combination of UA-LDS-DLLME with GC-QQQ-MS offers an alternative analytical approach for the sensitive detection of these designer benzodiazepines in urine matrix for clinical and medico-legal purposes.
authors.affiliation: Department of Forensic Science, Fujian Police College, Fuzhou, 350007, PR China; Centre for Forensic Science, School of Mathematical and Physical Sciences, University of Technology, Sydney, 2007, Australia. Electronic address: mlatfy@hotmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Forensic Science, Fujian Police College, Fuzhou, 350007, PR China.
authors.forename: Binling
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Forensic Science, Fujian Police College, Fuzhou, 350007, PR China.
authors.forename: Kefang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Centre for Forensic Science, School of Mathematical and Physical Sciences, University of Technology, Sydney, 2007, Australia.
authors.forename: Shanlin
authors.initials: S
authors.lastname: Fu
mesh_terms: D001569:Benzodiazepines / Q000652:urine*; D002491:Central Nervous System Agents / Q000652:urine*; D015198:Designer Drugs / Q000493:pharmacokinetics; D003975:Diazepam / Q000031:analogs & derivatives* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D059627:Liquid Phase Microextraction / Q000379:methods*; D013010:Sonication / Q000379:methods; D015813:Substance Abuse Detection / Q000379:methods
chemical_list: D002491:Central Nervous System Agents; D015198:Designer Drugs; D001569:Benzodiazepines; C017928:phenazepam; C044610:etizolam; D003975:Diazepam
keywords: Designer benzodiazepines; Dispersive liquid–liquid microextraction; Gas chromatography–triple quadrupole mass spectrometry; Response surface methodology; Ultrasonication