Accurate 24-h urine cystine quantification for patients on cystine-binding thiol drugs.

Cystinuria is a rare disorder resulting in development of recurrent kidney stones, adversely affecting patient quality of life. The goal of cystinuria management is to reduce stone formation by increasing cystine solubility in urine, which includes lowering the urinary cystine level below its solubility limit. Treatment usually involves alkalinization of the urine and often requires initiating pharmacotherapy with a cystine-binding thiol drug (CBTD) such as tiopronin; however, proper dose adjustment requires accurate measurement of urinary cystine.

Differentiating medicinal from illicit use in positive methamphetamine results in a pain population.

In addition to illicit methamphetamine, there are prescription and over-the-counter medications that, if ingested, may yield positive methamphetamine (MAMP) results on laboratory urine drug tests. The purpose of the study is to estimate the prevalence of medicinal and illicit MAMP in the pain population using chiral analysis to determine the relative amounts of the d and l-MAMP enantiomers. This retrospective analysis included the LC-MS/MS results and prescriber provided medication histories of 485,889 de-identified urine specimens from patients treated for pain.

Stability of pain-related medications, metabolites, and illicit substances in urine.

Background: Effective urine drug testing requires an understanding of the stability of medications, metabolites and other substances excreted in the urine matrix. When the testing results do not fit the clinical picture, physicians frequently request repeat testing of the original specimen in order to corroborate the results. We determined the stability in urine of various medications, metabolites, and illicit substances commonly requested for testing by physicians treating patients with pain and pain-related disorders.

Illicit drug use correlates with negative urine drug test results for prescribed hydrocodone, oxycodone, and morphine.

Background: A number of studies indicate that 10.8%-34% of patients with chronic pain use illicit drugs. One hypothesis for this occurrence is that some patients may be supplementing their prescription medications with illicit drugs.

Improvement of pain physicians' practices of opioid management: population-based urinary excretion data.

Background: Physicians treating patients for chronic pain have limited means of determining whether a person is taking their medications as prescribed and are not taking extra medication. Complicating patient treatment regimens is the fact that pain physicians' prescribing practices may come under scrutiny by the Drug Enforcement Agency and other licensing agencies. If questioned, doctors can be hard-pressed to substantiate that their particular practices meet the established standard of care.

Determination of illicit drug cutoff values in a pain patient population.

Background: When properly selected, cutoff levels minimize the reporting of false negative and false positive test results and allow the laboratory to accurately determine the prevalence of marijuana, cocaine and methamphetamine use. Selecting the ideal cutoff requires the collection of drug excretion data for a large patient population to determine the expected range of drug concentrations. The cutoff can then be set to capture a high percentage of positives at a concentration within the dynamic range of the method.

Determination of medication cutoff values in a pain patient population.

Background: Clinical laboratories are required to establish reference intervals for all the analytes tested, and these are provided along with the test results. In contrast, laboratories testing for pain medications use cutoffs established by the manufacturers of immunoassay reagents. These cutoffs may be inappropriate for monitoring patients being treated for chronic pain with opioid therapy because the cutoffs are set too high.

An improved method of determining ethanol use in a chronic pain population.

Background: Determination of ethanol use in the pain patient population being treated with chronic opioid therapy is critically important to the treating physician. Urinary ethanol, ethyl glucuronide (EtG), and ethyl sulfate (EtS) have been used to identify alcohol use. Because urine samples are shipped to reference laboratories, the possibility of glucose fermentation during transit producing ethanol complicates interpretation.

Illicit drug use in the pain patient population decreases with continued drug testing.

Background: A major concern of physicians treating pain patients with chronic opioid therapy and similar drugs is determining whether the patients are also using illicit drugs. This is commonly determined by urine drug testing (UDT). However, there are few studies on whether or not monitoring patients by this technique decreases illicit drug use.

Improved detection of ethyl glucuronide and ethyl sulfate in a pain management population using high-throughput LC-MS/MS.

Background: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) have been proposed as markers for detecting alcohol use because they exhibit extended excretion lifetimes when compared with ethanol; however, their presence is not considered as absolute proof of alcohol use. Two methods are currently used for the detection and quantitation of EtG: immunoassay and mass spectrometry. The purpose of this study was to provide more patient data to better compare the two methods.

Reference intervals: a novel approach to detect drug abuse in a pain patient population.

Background: pain physicians have few objective ways of determining which of their patients are drug abusers. Traditionally, these include psychological tests, physical examination, patient history, and urine drug testing. The traditional urine drug testing information provided to pain physicians mainly identifies patient compliance or drug diversion with qualitative information, that is, the patient is positive or negative for the presence of the drug in excreted urine.

Observations of medication compliance by measurement of urinary drug concentrations in a pain management population.

Background: One of the major concerns of physicians treating pain patients with opioids is to determine whether the patients are compliant, and this is commonly determined by urine drug testing. There is limited information on which drugs these patients are most compliant with. There is also limited information as to how compliance is defined in terms of cutoffs.

Anomalous observations of hydrocodone in patients on oxycodone.

Background: Urine drug monitoring is used by physicians treating chronic pain patients with opioid therapy. Patients are tested in part to insure that they are not taking other drugs. Therefore, the finding of hydrocodone in a patient who is only prescribed oxycodone has clinical implications.

Marijuana correlates with use of other illicit drugs in a pain patient population.

Background: A significant number of chronic pain patients may use marijuana. Physicians treating those patients can benefit by knowing whether their patients using marijuana are at higher risk for using other illicit drugs such as cocaine and/or methamphetamine.

Objective: Our objective was to determine whether marijuana-using chronic pain patients have a higher incidence of cocaine and/or methamphetamine use.

An evaluation of the diagnostic accuracy of liquid chromatography-tandem mass spectrometry versus immunoassay drug testing in pain patients.

Background: Immunoassay screening is used by pain physicians to determine compliance with controlled substances. Because clinical use of pain medications is different from illicit drug use, there is a need to evaluate the level of diagnostic accuracy of this procedure for the pain patient.

Objective: To compare the results of automated screening by immunoassay with analysis by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) in identifying pain patients using illicit drugs and pain patients excreting low concentrations of their prescribed medications.

Comparison of clonazepam compliance by measurement of urinary concentration by immunoassay and LC-MS/MS in pain management population.

Background: Physicians determine patient compliance with their medications by use of urine drug testing. It is known that measurement of benzodiazepines is limited by immunoassay specificity and cutoff limits and therefore does not offer physicians an accurate picture of their patients' compliance with these medications. A few studies have used lower cutoffs to demonstrate patient compliance.

Anomalous observations of codeine in patients on morphine.

Urine drug monitoring is used by physicians treating chronic pain patients with opioid therapy. Patients are tested in part to insure that they are not taking other drugs. Therefore, the finding of codeine in a patient who is only prescribed morphine has clinical implications.

LC-MS/MS extends the range of drug analysis in pain patients.

The current study addresses the distribution of low concentrations of excreted drugs in the pain patient population in an effort to establish a more rational set of cutoffs for this cohort. To wit, 19 analytes in approximately 8000 urine specimens from pain patients were measured using liquid chromatography tandem mass spectroscopy (LC-MS/MS) methodology. The lower limits of quantitation for the LC-MS/MS were set as the nominal cutoffs for the determination of positive and negative results.

Unstable propoxyphene metabolite excreted in human urine is detected by liquid chromatography-tandem mass spectrometry.

A "dilute and shoot" method for measuring norpropoxyphene in human urine using liquid chromatography-tandem mass spectrometry distinguishes two different metabolites of propoxyphene, norpropoxyphene (m/z 326) and a dehydrated rearrangement product (m/z 308). The metabolite formed from the rearrangement and dehydration of norpropoxyphene is excreted in human urine and also may be formed from the chemical degradation of norpropoxyphene. Previously, these two metabolites were indistinguishable by gas chromatography- mass spectrometry methods that use an alkaline extraction that converts norpropoxyphene into its rearrangement product.

6-Acetylmorphine detected in the absence of morphine in pain management patients.

Liquid chromatography tandem mass spectrometry was used to identify and confirm the presence of 6-acetylmorphine and morphine in 22,361 urines of pain management patients. Thirty urines tested positive for 6-acetylmorphine above a cutoff of 10 ng/mL. Twenty-three percent of the patients with urinary concentrations of 6-acetylmorphine above 10 ng/mL had urinary morphine concentrations below 300 ng/mL.