Benzodiazepines analysis

HPLC/DAD is very important in benzodiazepine analysis. After enzymatic cleavage of the conjugate, the individual metabolites of the benzodiazepines can be clearly distinguished from each other and identified in the chromatogram, so that, for example, the co-consumption of bromazepam when diazepam therapy is in progress can be detected. In sample material of low concentration, for example, the determination of several metabolites of the same starting substance considerably improves the quality of the analytical results. The limit of detection of HPLC is more than adequate in the region of 10-20 ng/ml for routine and confirmatory analysis. 

Authors are designed row sensitive and selective test-systems for analysis of heavy metals, active chlorine, phenols, nitrates, nitrites, phosphate etc. for analysis of objects of an environment and for control of ions Ee contents in the technological solutions of KH PO, as well as for testing some of pharmacological psychotropic daigs alkaloids (including opiates), cannabis as well as pharmaceutical preparations of phenothiazines, barbiturates and 1,4-benzodiazepines series too. 

Benzodiazepines (24b) exist as such and not as the antiaromatic 3//-tautomers 24a [73JCS(P1)2543 83H2173]. A different tautomer (5H) was observed for Tofizopam (25) using and NMR (74CB3894) and X-ray structure analysis [86JST(147)143]. Tire same behavior is observed... 

Barker MJ, Greenwood KM, Jackson M, et al Cognitive effects of long-term benzodiazepine use a meta-analysis. CNS Drugs 18 37M8, 2004... 

Applications APCI-MS is often more widely applicable than ESI-MS to the analysis of classes of compounds with a low molecular weight, such as basic drugs and their metabolites, antibiotics, steroids, oestrogens, benzodiazepines, pesticides, surfactants, and most other organic compounds amenable to El. LC-APCI-MS has been used to analyse PET extracts obtained by a disso-lution/precipitation procedure [147]. Other applications of hyphenated APCI mass spectrometric techniques are described elsewhere LC-APCI-MS (Section 7.33.2) and packed column SFC-APCI-MS (Section 73.2.2) for polar nonvolatile organics. 

Ethyl 10-chloro-7-methyl-6-oxo-l lb-phenyl-5,6,7,1 lb-tetrahydroisoxazolo[2, 3-separable mixture of 6-chloro-4-(2-ethoxycarbonyl-2-formyl-l-phenylvinyl)-l-methyl-3,4-dihy-dro-2(l //)-quinoxalinone (564), 4-(2-benzoyl-2-ethoxycarbonylvinyl)-6-chloro-1-methyl-3,4-dihydro-2(l//)-quinoxalinone (565), and 6-chloro-l-methyl-3,4-dihydro-2(l//)-quinoxalinone (567) (EtOH, reflux, 21 h 2%, 8%, and 20%, respectively, after separation structures 564 and 565 were checked by X-ray analysis).106... 

Bishop KI and Curran HY (1995). Psychopharmacological analysis of implicit and explicit memory A study with lorazepam and the benzodiazepine antagonist flumazenil. Psychopharmacology, 121, 267-278. 

Piecoro LT, Browning SR, Prince TS et al. (2000) A database analysis of potentially inappropriate drug use in an elderly medicaid population. Pharmacotherapy 20(2) 221-228 Ray WA, Thapa PB, Gideon P (2000) Benzodiazepines and the risk of falls in nursing home residents. J Am Geriatr Soc 48(6) 682-685... 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

Cooper TB. 1988. Gas-liquid chromatography of antidepressant, antipsychotic and benzodiazepine drugs in plasma and tissues. Neuromethods, Vol. 10 Analysis of Psychiatric Drugs. Boulton AA, Baker GB, Coutts RT, editors. New Jersey Humana Press pp. 65-98. 

Several additional useful publications demonstrating practical applications of CE/MS methods for neurotransmitter analysis and neuropharmaceutical studies are those of Larsson and Lutz (2000) (neuropeptides including substance P) Hettiarachchi et al. (2001) (synthetic opioid peptides) Varesio et al. (2002) (amyloid-beta peptide) Zamfir and Peter-Katalinic (2004) (gangliosides) Peterson et al. (2002) (catecholamines and metanephrines) Cherkaoui and Veuthey (2002) (fluoxetine) and Smyth and Brooks (2004) (various lower molecular weight molecules including benzodiazepines, steroids, and cannabinols). 

Quaglia, M. G., Farina, A., Bossu, E., and Dell aquila, C. (1995). Analysis of non-benzodiazepinic anxiolytic agents by capillary zone electrophoresis. /. Pharm. Biomed. Anal. 13, 505 — 509. 

Zhu et al. coupled OT-CEC to ESI/MS for the analysis of /i-blockers and benzodiazepines. The authors described the use of a polymeric surfactant as a stationary-phase coating that enabled minimal surfactant introduction in the MS compared to MEKC—ESI/MS, thus avoiding interferences from non-voIatile micelles in ESI/MS. ... 

Wong, G., Koehler, K.F., Skolnick, P., Gu, Z.-Q., Ananthan, S., Schonholzer, P., Hunkeler, W., Zhang, W., and Cook, J.M. Synthetic and computer-assisted analysis of the structural requirements for selective, high-afhnity ligand binding to diazepam-insensitive benzodiazepine receptors./. Med. Chem. 1993, 36, 1820-1830. 

Buckley NA, McManus PR (2002) Fatal toxicity of serotoninergic and other antidepressant drugs analysis of United Kingdom mortality data. BMJ 325 1332-1333 Buckley NA, Dawson AH, Whyte IM, O Connell DL (1995) Relative toxicity of benzodiazepines in overdose. BMJ 310 219-221... 

Enkelmann R (1991) Alprazolam versus buspirone in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology (Berl) 105 428-432 Faravelli C, Rosi S, Truglia E (2003) Treatments benzodiazepines. In Nutt DJ, BaUenger JC (eds) Anxiety disorders. Blackwell Science, Oxford, pp 315-338 Fawcett J, Barkin RL (1998) A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry 59 123-127 Febbraro GA, Clum GA (1998) Meta-analytic investigation of the effectiveness of self-regulatory components in the treatment of adult problem behaviors. Clin Psychol Rev 18 143-161... 

Benzodiazepines (BZDs) are commonly prescribed in the psychiatric practice to treat anxiety, insomnia, and unpleasant side effects associated with other psychotropic agents. While early case-control studies found that maternal BZD exposure increased the risk of cleft lip and cleft palate, a recent meta-analysis (Dolovich et ah, 1998) examining pooled data from cohort studies published between 1966 and 1998 found no association between antenatal BZD exposure and oral cleft or other major malformations. However, when examining case-control studies published during this period, the authors did find a small, but significant, odds ratio of... 

Dolovich, L., Addis, A., Vaillancourt, J.M.R., Power, J.D.B., Koren, G., and Einarson, T.R. (1998) Benzodiazepine use in pregnancy and malformations ot oral clefts meta-analysis of cohott and case-control studies. BMJ 317 839—843. 

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