A Novel Reductive Transformation of Oxazepam to Nordiazepam Observed During Enzymatic Hydrolysis

Fu, Shanlin; Lewis, John H.; Wang, Hongjie; Keegan, Jim; Dawson, Michael J.

doi:10.1093/jat/34.5.243

Cited by 31 publications

(21 citation statements)

References 19 publications

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“…Of interest, enzymatic hydrolysis has also been shown to transform oxazepam to nordiazepam, thus preventing accurate identification of parent drug. 32 Laboratories that utilize hydrolysis reactions as a component of routine sample preparation should include glucuronide conjugate material as a quality control sample for every analytical batch, to assure that the reaction occurs according to assay specifications. Alternatively, measurement of the "free" drug analyte, in conjunction with direct analysis of glucuronide conjugates eliminates the need for hydrolysis reactions, can improve positivity rates of some drugs, and can offer information about a patient's metabolic phenotype that may not be realized otherwise.…”

Section: Hydrolysismentioning

confidence: 99%

Demystifying Analytical Approaches for Urine Drug Testing to Evaluate Medication Adherence in Chronic Pain Management

McMillin¹,

Slawson²,

Marin³

et al. 2013

Journal of Pain & Palliative Care Pharmacotherapy

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This comprehensive review of analytical methods used for urine drug testing for the support of pain management describes the methods, their strengths and limitations, and types of analyses used in clinical laboratories today. Specific applications to analysis of opioid levels are addressed. Qualitative versus quantitative testing, immunoassays, chromatographic methods, and spectrometry are discussed. The importance of proper urine sample collection and processing is addressed. Analytical explanations for unexpected results are described. This article describes the scientific basis for urine drug testing providing information which will allow clinicians to differentiate between valid and questionable claims for urine drug testing to monitor medication adherence among chronic pain patients.

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Section: Hydrolysismentioning

confidence: 99%

Demystifying Analytical Approaches for Urine Drug Testing to Evaluate Medication Adherence in Chronic Pain Management

McMillin¹,

Slawson²,

Marin³

et al. 2013

Journal of Pain & Palliative Care Pharmacotherapy

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“…Moreover, prolonged incubation at temperatures >50°C can lead to degradation and a loss of benzodiazepine drugs in urine (34). Another unique limitation is the reduction of oxazepam to nordiazepam during enzyme hydrolysis (35). The formation of nordiazepam from oxazepam, which ranged from <0.04% to 2.5%, was correlated to incubation temperature, incubation time, oxazepam concentration, and β-glucuronidase enzyme concentration from the following sources: E. coli, P. vulgate, and H. pomatia (35).…”

Section: Hydrolysis Of Benzodiazepine Drugsmentioning

confidence: 99%

“…Another unique limitation is the reduction of oxazepam to nordiazepam during enzyme hydrolysis (35). The formation of nordiazepam from oxazepam, which ranged from <0.04% to 2.5%, was correlated to incubation temperature, incubation time, oxazepam concentration, and β-glucuronidase enzyme concentration from the following sources: E. coli, P. vulgate, and H. pomatia (35). The formation of nordiazepam had the potential to lead to a false-positive result that should be interpreted with caution (35).…”

Section: Hydrolysis Of Benzodiazepine Drugsmentioning

confidence: 99%

Opiate & Benzodiazepine Confirmations: To Hydrolyze or Not to Hydrolyze is the Question

Johnson-Davis

2018

The Journal of Applied Laboratory Medicine

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Background: Opiates/opioids and benzodiazepines are commonly prescribed drug therapies for acute and chronic pain. Urine drug testing is often employed to assess adherence to these mediations. Opioids and benzodiazepines are drug classes that undergo extensive metabolism through glucuronidation/sulfation. Conjugated glucuronide and sulfate drug metabolites can be difficult to detect by immunoassay and mass spectrometry methods. Consequently, false-negative or false-positive results can have a damaging impact on patient care. A common dilemma among drug-testing laboratories is whether to perform preanalytical hydrolysis to increase detection of drugs that are highly conjugated as metabolites. Methods: The purpose of hydrolysis is to cleave the glucuronide or sulfate compounds to enhance analyte detection by increasing the parent drug concentration of those drugs that are primarily metabolized by glucuronidation or sulfation. Hydrolysis procedures can be performed by acid, base, or enzyme sources (β-glucuronidase). Results: Preanalytical hydrolysis can improve the overall detection of most opioids and benzodiazepine drugs. However, the limitation of this procedure is that the process can be time-consuming and prolong the turnaround time to result. In addition, chemical hydrolysis has the potential to degrade opioid and benzodiazepine drugs, whereas incomplete hydrolysis and variable hydrolysis efficiencies can occur with an enzymatic approach. Conclusions: Preanalytical hydrolysis can improve the sensitivity of drug detection for drug classes such as opiates/opioids and benzodiazepines, which are highly metabolized by glucuronidation and sulfation and should be implemented in analytical procedures to convert conjugated metabolites into the free (unbound) form. IMPACT STATEMENT This article summarizes the advantages and limitations of performing preanalytical hydrolysis of urine samples in a pain management population. The purpose of hydrolysis is to increase the analytical sensitivity of drug detection. Hydrolysis method comparison studies have demonstrated an increase in analyte detection to nonhydrolyzed samples. These studies have shown that the sample preparation and analytical technique can have an impact on the accuracy of the results. Laboratories will need to develop drug assays to reduce the number of reported false-positive or false-negative results to support testing in a pain management population.

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“…However, long‐term use of BZPs can lead to physical and psychological addiction. In addition to their therapeutic usage, BZPs are also frequently encountered in forensic toxicology due to their misuse or abuse as their use has been reported in relation to suicide attempts, road accidents, drug‐facilitated sexual assaults, and other crimes . Hence, the determination of BZPs in biological specimens and common drinks is critical for both medical and forensic sciences.…”

Section: Introductionmentioning

confidence: 99%

Poly(methacrylic acid-ethylene glycol dimethacrylate-N-vinylcarbazole) monolithic column for the enrichment of trace benzodiazepines from urine and beer samples

2017

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A sensitive microextraction method based on a new poly(methacrylic acid-ethylene glycol dimethacrylate-N-vinylcarbazole) monolithic capillary column, coupled with gas chromatography and electron capture detection, was established for the determination of three benzodiazepines (estazolam, alprazolam, and triazolam) in urine and beer samples. Owing to the abundant π electrons and polar surface of N-vinylcarbazole, N-vinylcarbazole-incorporated monolith showed a higher extraction performance than neat poly(methacrylic acid-ethylene glycol dimethacrylate) because of the enhanced π-π stacking interactions derived from the π-electron-rich benzene groups from N-vinylcarbazole. The monolith exhibited a homogeneous and continuous structure, good permeability, and a long lifetime. Factors affecting the extraction such as solution pH, salt concentration, sample volume, desorption solvent, and desorption volume were investigated. Under the optimized conditions, limits of detection of 0.011-0.026 ng/mL were obtained. The one-column and column-to-column precision values were ≤7.2 and ≤9.8%, respectively. The real samples were first diluted with deionized water and then treated by the monolith microextraction before gas chromatography analysis. The recoveries were 81.4-93.3 and 83.3-94.7% for the spiked samples, with relative standard deviations of 4.1-8.1 and 3.8-8.5%, respectively. This method provides an accurate, simple, and sensitive detection platform for drug analysis.

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A Novel Reductive Transformation of Oxazepam to Nordiazepam Observed During Enzymatic Hydrolysis

Cited by 31 publications

References 19 publications

Demystifying Analytical Approaches for Urine Drug Testing to Evaluate Medication Adherence in Chronic Pain Management

Demystifying Analytical Approaches for Urine Drug Testing to Evaluate Medication Adherence in Chronic Pain Management

Opiate & Benzodiazepine Confirmations: To Hydrolyze or Not to Hydrolyze is the Question

Poly(methacrylic acid-ethylene glycol dimethacrylate-N-vinylcarbazole) monolithic column for the enrichment of trace benzodiazepines from urine and beer samples

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