Monitoring buprenorphine in patients on medication-assisted treatment.

BACKGROUND: Buprenorphine is used for medication-assisted treatment of opioid dependence. PURPOSE: Monitoring of medication adherence involves testing of urine or oral fluid for the drug or its metabolite. METHODS: Quantitative results using liquid chromatography tandem mass spectrometer testing defined the excretion pattern of the drug and its metabolites. RESULTS: Frequency distribution curves of buprenorphine and norbuprenorphine describe the expected drug concentrations of patients on this medication. CONCLUSION: Urine and oral fluid drug testing can be used to monitor adherence in this population.

Letter to Editor: Observations of Deception in Urine Drug Testing.

OBJECTIVE: Determining deception in urine drug testing. Some of the patients undergoing urine drug tests have not taken the prescribed drug and attempt to deceive the laboratory test by placing the parent drug in the collection cup. METHODS: One of the ways to determine if this is occurring is to monitor the major metabolite of the drug. By using the metabolite/parent drug ratio this attempt at deception can be uncovered. RESULTS: Of the five drugs we examined, oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl, we found buprenorphine to be the most prevalent drug to this type of deception. CONCLUSION: Deception can be identified using the metabolite/parent drug ratio.

Estimates of Drug Metabolism Using Drug Excretion Concentrations.

We propose that quantitative urine drug concentrations from LC-MS/MS measurements can be used to estimate zero and first order pharmacokinetics of the drugs oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl. We observed the ratio of metabolite to parent drug could be used for this estimate. As the amount of observed parent drug increased, the metabolic ratio decreased, indicating a shift from first order to zero order metabolism. After making assumptions of bioavailability, percent of drug excreted into urine, we developed estimates of the saturating dosages for these drugs.

Lower Cutoffs for LC-MS/MS Urine Drug Testing Indicates Better Patient Compliance.

BACKGROUND: Urine drug testing is used by health care providers to determine a patient's compliance to their prescribed regimen and to detect non-prescribed medications and illicit drugs. However, the cutoff levels used by clinical labs are often arbitrarily set and may not reflect the urine drug concentrations of compliant patients. OBJECTIVES: Our aim was to test the hypothesis that commonly used cutoffs for many prescribed and illicit drugs were set too high, and methods using these cutoffs may yield a considerable number of false-negative results. The goals of this study were to outline the way to analyze patient results and estimate a more appropriate cutoff, develop and validate a high sensitivity analytical method capable of quantitating drugs and metabolites at lower than the commonly used cutoffs, and determine the number of true positive results that would have been missed when using the common cutoffs. STUDY DESIGN: This was a retrospective study of urine specimens submitted for urine drug testing as part of the monitoring of prescription drug compliance described in chronic opioid therapy treatment guidelines. SETTING: The study was set in a clinical toxicology laboratory, using specimens submitted for routine analysis by health care providers in the normal course of business. METHODS: Lognormal distributions of test results were generated and fitted with a trendline to estimate the required cutoff level necessary to capture the normal distributions of each drug for the patient population study. A validated laboratory derived liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis capable of achieving the required cutoff levels was developed for each drug and/or metabolite. RESULTS: The study shows that a lognormal distribution of patient urine test results fitted with a trendline is appropriate for estimating the required cutoff levels needed to assess medication adherence. The study showed a wide variation in the false-negative rate, ranging from 1.5% to 94.3% across a range of prescribed and illicit drugs. LIMITATIONS: The patient specimens were largely sourced from patients in either a long-term pain management program or in treatment for substance use disorder in the US. These specimens may not be representative of patients in other types of treatment or in countries with different approaches to these issues. CONCLUSIONS: The high-sensitivity method reduces false-negative results which could negatively impact patient care. Clinicians using less sensitive methods for detecting and quantifying drugs and metabolites in urine should exercise caution in assessing patient adherence using and changing the treatment plan based on those results. KEY WORDS: Urine drug testing, patient adherence, clinical toxicology, immunoassay, LC-MS, definitive drug testing, REMS, negative test results, false negative.

Stereoisomers of carotenoids: spectroscopic properties of locked and unlocked cis-isomers of spheroidene.

A systematic optical spectroscopic and computational investigation of a series of locked-cis-isomers of spheroidene has been carried out with the goal being to better understand the relationships between stereochemistry, photochemistry, photophysics and biological function of geometric isomers of carotenoids. The spectroscopic properties of 15,15'-locked-cis-spheroidene, 13,14-locked-cis-spheroidene, 11, 12-locked-cis-spheroidene in solution are compared with those observed for unlocked spheroidene. The locked-cis bonds are incapable of undergoing cis-to-trans isomerization and therefore provide an effective means of exploring the relationship between specific stereoisomers and molecular spectroscopy. Samples of the molecules were purified using a high performance liquid chromatography (HPLC) apparatus equipped with a diode array detector, which records the absorption spectra immediately as the molecules emerge from the column and prior to any isomerization that might occur. For several stable isomers, resonance Raman (rR) spectroscopy was carried out to assign their configurations. Quantum computations of absorption spectra were performed using ZINDO/S and also MNDO-PSDCI methods employing nearly full single and double configuration interaction within the pi-electron manifold. Also, for a few test cases, ground state minimizations were done using density functional methods (B3LYP/6-31G(d)). The MNDO-PSDCI methods coupled with the density functional ground state minimization provide an accurate assignment of the positions of the 2(1)Ag - , 1(1)Bu +, and 1(1)Ag + excited states and also address the nature of the forbidden 1(1)Bu - state, whose location is uncertain for polyenes and carotenoids. We demonstrate that the configurational description of the 1(1)Bu - state is sufficiently unique to preclude assignment of its energy based on the characterization of surrounding excited singlet states. The experimental and computational data also offer important insights into the photochemical and photophysical properties of stereoisomers of carotenoids.

Resonance Raman spectroscopy of carotenoids in Photosystem II core complexes.

Resonance Raman (RR) spectroscopy has been used to examine the configuration of the carotenoids bound to Synechocystis PCC 6803 Photosystem II (PS II) core complexes. The excitation wavelengths used (514.5, 488.0, 476.5 and 457.9 nm) span the absorption bands of all of the approximately 12-17 neutral carotenoids in the PS II core complex. The RR spectra of the two carotenoids associated with the D1-D2 polypeptides (Car507 and Car489) of the reaction center are extracted via light versus dark difference experiments measured at 20 K. The RR results are consistent with all-trans configurations for both Car507 and Car489 and indicate that majority of the other carotenoids in the PS II core complex must also be in the all-trans configuration. The configuration of beta-carotene is relevant to its proposed function as a molecular wire in the secondary electron-transfer reactions of PS II.

Raman spectra and normal coordinate analyses of low-frequency vibrations of oxo-bridged manganese complexes.

The active sites of certain metalloenzymes involved in oxygen metabolism, such as manganese catalase and the oxygen-evolving complex of photosystem II, contain micro -oxo-bridged Mn clusters with ligands that include H(2)O and micro (1,3)-carboxylato bridges provided by protein side chains. In order to understand better the vibrational spectra of such clusters, the low-frequency resonance Raman spectra of a series of structurally characterized Mn-oxo model complexes were examined. The series includes complexes of the type [Mn(2)(O)(OAc)(2)(bpy)(2)(L)(2)] and [Mn(2)(O)(2)(OAc)(bpy)(2)(L)(2)], where bpy=2,2'-bipyridine, OAc=acetate and L=H(2)O or Cl(-). Complexes containing the isotopomers OAc- d(3) and D(2)O, as well as those containing both isotopomers, were also examined. Normal coordinate analyses (NCA) were performed on the various complexes using theGF matrix method. Selected vibrational modes in the 200-600 cm(-1) region were assigned based on the spectra and NCA, which identify vibrational modes arising from the metal-ligand bonds. These results will be useful in interpreting the vibrational spectra obtained from metalloproteins containing Mn-oxo complexes in their active sites.