Long-Term Stability of Abused Drugs and Antiabuse Chemotherapeutical Agents Stored at -20 C

Abstract

Stability is an important consideration in the use of specimens for accurate determination of analyte concentrations. To determine the long-term stability for analytes routinely analyzed by mass spectrometry in this laboratory, quality-control (QC) results were plotted versus time. The time required for the initial concentration to reach a specified level of deviation (i.e., 15%) was then determined from the slopes. QCs were prepared at 1-3 concentrations in drug-free matrix and stored at approximately -20 degrees C; urines were fortified with 1% sodium fluoride; plasmas (except for cocaines) were prepared with heparin. For cocaine and metabolites, the plasma was either fortified with 2% sodium fluoride or with 2% sodium fluoride and 1 mg% physostigmine after adjustment of the plasma pH to 6.0. In urine, amphetamine, methamphetamine, codeine, morphine, benzoylecgonine (BZE), and 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCA) slopes did not exceed a 15% deviation before 852 days. Cocaine, however, reached a 15% reduction at 165 days. When cocaine and BZE were prepared in plasma with just 2% sodium fluoride, negative slopes reached 15% deviation within 154 and 111 days, respectively. Further fortification with physostigmide and adjustment of the pH extended this time frame significantly. Delta9-Tetrahydrocannabinol (THC) and THCA in plasma had negative slopes that deviated by 15% just prior to one year. l-Alpha-acetylmethadol (LAAM), methadone, and their N-demethylated metabolites in urine did not have any negative slopes exceeding 15% before 686 days. Several of the compounds had positive slopes. Those for 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine reached the 15% mark within 98 days. Those for LAAM, norLAAM, and dinorLAAM were concentration dependent. The 25-ng/mL controls reached 15% at 158-216 days. The 700-ng/mL controls reached 15% at 784-1340 days. In plasma, only naltrexone and buprenorphine displayed negative slopes at all three concentrations, reaching the 15% mark as early as 576 and 272 days, respectively. LAAM, norLAAM, dinorLAAM, ibogaine, 6-beta-naltrexone, risperidone, and 9-OH-risperidone did not exceed a 15% deviation before 416 days. To attempt to validate this method, two sets of clinical plasma samples that had been analyzed for buprenorphine were reanalyzed 644 and 869 days after the initial analyses. Those reanalyzed after 644 days were not statistically different from initial analyses, whereas those stored for 869 days were statistically different (p < 0.05). As the average time to reach 15% deviation for the three concentrations of buprenorphine QCs was 782 days, this suggests that extrapolation of QC results gathered over time may provide a reliable method to estimate long-term stability limits for drugs stored under the same conditions as the QC samples.

A Liquid Chromatographic-Electrospray Ionization-Tandem Mass Spectrometric Method for Determination of Buprenorphine, Its Metabolite, norBuprenorphine, and a Coformulant, Naloxone, That Is Suitable for in Vivo and in Vitro Metabolism Studies

“…When samples were extracted, reconstituted, and stored in autosampler vials at Ϫ20°C, they were found to give accurate and precise results for up to 3 days of storage (Table 2). Previously, through reanalysis of clinical samples for buprenorphine, it was shown that statistically similar results were achieved for samples stored for 644 days at Ϫ20°C, but for samples stored 869 days under these conditions, the percentage of change in concentrations was significantly different (29). These direct results agreed well with those predicted from plots of concentrations in fortified sample versus time and extrapolation to a point where 15% deviation was found (i.e., 598 days).…”

“…Short-and long-term stability studies on these analytes have been limited to buprenorphine (20,28,29). Current stability experiments focused on storage conditions that are relevant to the day-to-day analyses of these compounds.…”

Agreement between Maternal Cannabis Use during Pregnancy according to Self-Report and Urinalysis in a Population-Based Cohort: The Generation R Study

“…However, several studies have shown that change in concentrations of 11-nor-⌬ 9-THC-9-COOH after long-term storage was not extensive ( ! 15%) [29,30] . Second, we cannot rule out that women may wonder about specific aims for urine collection.…”

Cocaine and Metabolites Urinary Excretion after Controlled Smoked Administration*

“…We examined the possibility that metabolite concentrations were lower due to deterioration during storage (16). Urine specimens were stored frozen for an extended timeframe at −20°C before analysis in this study.…”