Observations on hydrocodone and its metabolites in oral fluid specimens of the pain population: Comparison with urine

2014 ◽  
Vol 10 (3) ◽  
pp. 177 ◽  
Author(s):  
Jennifer M. Cao, BS ◽  
Joseph D. Ma, PharmD ◽  
Candis M. Morello, PharmD, CDE ◽  
Rabia S. Atayee, PharmD, BCPS ◽  
Brookie M. Best, PharmD, MAS
Keyword(s):  
Oral Fluid ◽  
Parent Drug ◽  
Reference Ranges ◽  
Microsoft Excel ◽  
Detection Rates ◽  
Medication Monitoring ◽  
Drug Concentrations ◽  
Population Comparison ◽  
Liquid Chromatography Tandem Mass ◽  
Linear Regressions

Objective: Hydrocodone undergoes metabolism via cytochrome P450 (CYP) 3A4 (N-demethylation) to norhydrocodone and via CYP2D6 (O-demethylation) to hydromorphone. Hydrocodone, hydromorphone, and norhydrocodone are excreted in urine and secreted in saliva. The goal was to characterize hydrocodone and its metabolites in oral fluid specimens of a pain population and compare to urine specimens.Design: This retrospective analysis included more than 8,500 oral fluid specimens and more than 250,000 urine specimens collected between March and June 2012 that were sent to Millennium Laboratories (San Diego, CA) and analyzed for hydrocodone, hydromorphone, and norhydrocodone using liquid chromatography-tandem mass spectrometry. Statistical analyses and linear regressions were conducted using Microsoft Excel® 2010 and OriginPro v8.6.Results: The median oral fluid concentrations of hydrocodone and norhydrocodone were 122 and 7.7 ng/mL, respectively. However, the oral fluid concentrations of hydromorphone were below detection in many specimens (<1 ng/mL). The positive detection rate of parent drug and metabolites in oral fluid (17-31 percent detection rates) was much lower than in urine (63-75 percent detection rates). The geometric median metabolic ratio (MR) of norhydrocodone to hydrocodone was 0.07 in oral fluid and 1.2 in urine. The observed hydrocodone oral fluid concentrations were approximately 10-fold greater than previously reported plasma concentrations.Conclusion: Oral fluid had a much lower norhydrocodone to hydrocodone MR compared to urine. Reference ranges for oral fluid drug concentrations should not be extrapolated from plasma ranges. The observed ranges of secreted hydrocodone and metabolite concentrations in oral fluid should help determine reference ranges for medication monitoring.

Monitoring nicotine intake from e-cigarettes: measurement of parent drug and metabolites in oral fluid and plasma

2017 ◽  
Vol 55 (3) ◽  
Author(s):  
Esther Papaseit ◽  
Magí Farré ◽  
Silvia Graziano ◽  
Roberta Pacifici ◽  
Clara Pérez-Mañá ◽  
...  
Keyword(s):  
Oral Fluid ◽  
Electronic Cigarettes ◽  
Biological Fluids ◽  
Parent Drug ◽  
Controlled Clinical Trial ◽  
Suitable Alternative ◽  
Tobacco Cigarette ◽  
Toxicological Studies ◽  
Liquid Chromatography Tandem Mass ◽  
Plasma Concentration Ratio

AbstractBackground:Electronic cigarettes (e-cig) known as electronic nicotine devices recently gained popularity among smokers. Despite many studies investigating their safety and toxicity, few examined the delivery of e-cig-derived nicotine and its metabolites in alternative biological fluids.Methods:We performed a randomized, crossover, and controlled clinical trial in nine healthy smokers. Nicotine (NIC), cotinine (COT), and trans-3′-hydroxycotinine (3-HCOT) were measured in plasma and oral fluid by liquid chromatography-tandem mass spectrometry after consumption of two consecutive e-cig administrations or two consecutive tobacco cigarettes.Results:NIC and its metabolites were detected both in oral fluid and plasma following both administration conditions. Concentrations in oral fluid resulted various orders of magnitude higher than those observed in plasma. Oral fluid concentration of tobacco cigarette and e-cig-derived NIC peaked at 15 min after each administration and ranged between 1.0 and 1396 μg/L and from 0.3 to 860 μg/L; those of COT between 52.8 and 110 μg/L and from 33.8 to 94.7 μg/L; and those of 3-HCOT between 12.4 and 23.5 μg/L and from 8.5 to 24.4 μg/L. The oral fluid to plasma concentration ratio of both e-cig- and tobacco cigarette-derived NIC peaked at 15 min after both administrations and correlated with oral fluid NIC concentration.Conclusions:The obtained results support the measurement of NIC and metabolites in oral fluid in the assessment of intake after e-cig use and appear to be a suitable alternative to plasma when monitoring nicotine delivery from e-cig for clinical and toxicological studies.

Quantitation of Δ8-THC, Δ9-THC, Cannabidiol and 10 Other Cannabinoids and Metabolites in Oral Fluid by HPLC–MS-MS

2020 ◽  
Author(s):  
Lin Lin ◽  
Piyadarsha Amaratunga ◽  
Jerome Reed ◽  
Pornkamol Huang ◽  
Bridget Lorenz Lemberg ◽  
...  
Keyword(s):  
Human Subject ◽  
High Performance ◽  
Oral Fluid ◽  
Solid Phase ◽  
Forensic Toxicology ◽  
High Concentration ◽  
Driving Impairment ◽  
Three Samples ◽  
Cannabidiolic Acid ◽  
Liquid Chromatography Tandem Mass

Abstract Quantitative analysis of Δ9-tetrahydrocannabinol (Δ9-THC) in oral fluid has gained increasing interest in clinical and forensic toxicology laboratories. New medicinal and/or recreational cannabinoid products require laboratories to distinguish different patterns of cannabinoid use. This study validated a high-performance liquid chromatography-tandem mass spectrometry method for 13 different cannabinoids, including (-)-trans-Δ8-tetrahydrocannabinol (Δ8-THC), (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), Δ9-tetrahydrocannabinolic acid-A (Δ9-THCA-A), cannabidiolic acid (CBDA), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabidiorcol (CBD-C1), cannabichromene (CBC), cannabinol (CBN) and cannabigerol (CBG), in oral fluid. Baseline separation was achieved in the entire quantitation range between Δ9-THC and its isomer Δ8-THC. The quantitation range of Δ9-THC, Δ8-THC and CBD was from 0.1 to 800 ng/mL. Two hundred human subject oral fluid samples were analyzed with this method after solid phase extraction. Among the 200 human subject oral fluid samples, all 13 cannabinoid analytes were confirmed in at least one sample. Δ8-THC was confirmed in 11 samples, with or without the presence of Δ9-THC. A high concentration of 11-OH-Δ9-THC or Δ9-THCCOOH (&gt;400 ng/mL) was confirmed in three samples. CBD, Δ9-THCA-A, THCV, CBN and CBG were confirmed in 74, 39, 44, 107 and 112 of the 179 confirmed Δ9-THC-positive samples, respectively. The quantitation of multiple cannabinoids and metabolites in oral fluid simultaneously provides valuable information for revealing cannabinoid consumption and interpreting cannabinoid-induced driving impairment.

scholarly journals Development and validation of quantitative analytical method for 50 drugs of antidepressants, benzodiazepines and opioids in oral fluid samples by liquid chromatography–tandem mass spectrometry

2020 ◽  
Author(s):  
Ana Carolina Furiozo Arantes ◽  
Kelly Francisco da Cunha ◽  
Marilia Santoro Cardoso ◽  
Karina Diniz Oliveira ◽  
Jose Luiz Costa
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Oral Fluid ◽  
Liquid Extraction ◽  
Simple Liquid ◽  
Tandem Mass ◽  
Liquid Liquid Extraction ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Abstract Purpose We developed and validated a method for quantitative analysis of 50 psychoactive substances and metabolites (antidepressants, benzodiazepines and opioids) in oral fluid samples using simple liquid–liquid extraction procedure followed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Method Oral fluid samples were collected using Quantisal™ device and extracted by liquid–liquid extraction with 1.0 mL of methyl tert-butyl ether and then analyzed using LC–MS/MS. Results The method attended method validation criteria, with limits of quantification as low as 0.5 and 1.0 ng/mL, and linearity between 0.5–50.0 ng/mL for antidepressants, 0.5–25.0 ng/mL for benzodiazepines and 1.0–50.0 ng/mL to opioids. During method validation, bias and imprecision values were not greater than 16 and 20%, respectively. Ionization suppression/enhancement bias results were not greater than 25%. No evidence of carryover was observed. Sample stability studies showed that almost all analytes were stable at 25 °C for 3 days and at 4 °C for 7 days. Freeze–thaw cycles stability showed that most antidepressants and opioids were stable under these conditions. Autosampler stability study showed that all analytes were stable for 24 h, except for nitrazepam and 7-aminoclonazepam. Thirty-eight authentic oral fluid samples were analyzed; 36.8% of the samples were positive for 2 drugs. Citalopram was the most common drug found, followed by venlafaxine. Conclusions The method was validated according to international recommendations for the 50 analytes, showing low limits of quantification, good imprecision and bias values, using simple liquid–liquid extraction, and was successfully applied to authentic oral fluid samples analysis.

scholarly journals Impact of Different Carbapenems and Regimens of Administration on Resistance Emergence for Three Isogenic Pseudomonas aeruginosa Strains with Differing Mechanisms of Resistance

2010 ◽  
Vol 54 (6) ◽  
pp. 2638-2645 ◽  
Author(s):  
Arnold Louie ◽  
Adam Bied ◽  
Christine Fregeau ◽  
Brian Van Scoy ◽  
David Brown ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Free Time ◽  
Wild Type ◽  
Resistance Mutations ◽  
Drug Concentrations ◽  
Cell Kill ◽  
Liquid Chromatography Tandem Mass ◽  
Full Period ◽  
Serial Samples ◽  
Isogenic Strains

ABSTRACT We compared drugs (imipenem and doripenem), doses (500 mg and 1 g), and infusion times (0.5 and 1.0 [imipenem], 1.0 and 4.0 h [doripenem]) in our hollow-fiber model, examining cell kill and resistance suppression for three isogenic strains of Pseudomonas aeruginosa PAO1. The experiments ran for 10 days. Serial samples were taken for total organism and resistant subpopulation counts. Drug concentrations were determined by high-pressure liquid chromatography-tandem mass spectrometry (LC/MS/MS). Free time above the MIC (time > MIC) was calculated using ADAPT II. Time to resistance emergence was examined with Cox modeling. Cell kill and resistance emergence differences were explained, in the main, by differences in potency (MIC) between doripenem and imipenem. Prolonged infusion increased free drug time > MIC and improved cell kill. For resistance suppression, the 1-g, 4-h infusion was able to completely suppress resistance for the full period of observation for the wild-type isolate. For the mutants, control was ultimately lost, but in all cases, this was the best regimen. Doripenem gave longer free time > MIC than imipenem and, therefore, better cell kill and resistance suppression. For the wild-type organism, the 1-g, 4-h infusion regimen is preferred. For organisms with resistance mutations, larger doses or addition of a second drug should be studied.

Methaqualone1 Overdose: Analytical Methodology, and the Significance of Serum Drug Concentrations

1973 ◽  
Vol 19 (6) ◽  
pp. 615-620 ◽  
Author(s):  
David N Bailey ◽  
Peter I Jatlow
Keyword(s):  
Liquid Chromatography ◽  
Polar Solvent ◽  
Parent Drug ◽  
Gas Liquid Chromatography ◽  
Back Extraction ◽  
Hexane Extraction ◽  
Analytical Methodology ◽  
Chloroform Extraction ◽  
Drug Concentrations ◽  
Reported Data

Abstract Methaqualone abuse and overdose have recently become "epidemic." We determined concentrations of the drug in serum in 15 cases of overdose by gas— liquid chromatography (GLC) and ultraviolet spectraphotometry (UV). Values by GLC were consistently lower than those determined by UV after chloroform extraction, but correlated well with those obtained by UV after hexane extraction. Our studies show that at least one chloroform extractable metabolite has a spectrum very similar to that of the parent drug. This may in part explain the lower results obtained by GLC and suggests that other reported data based on UV analysis of chloroform and ether extracts may be too high. Extraction with hexane, a less polar solvent, followed by back extraction into HCl provides an accurate UV method suitable for emergency use. Concentration of unchanged methaqualone in serum after overdose ranged from 2 mg/liter to 22 mg/liter in this series; those greater than 8 mg/liter were usually associated with unconsciousness.

scholarly journals SAT-166 Advantage and Trustworthy of Cortisol and Dexamethasone Evaluation in Different Biological Matrices in Patients with Adrenal Masses

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luana Lionetto ◽  
Roberta Maggio ◽  
Pina Lardo ◽  
Donatella De Bernardini ◽  
Fabiola Cipolla ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Adrenal Incidentaloma ◽  
Serum Cortisol ◽  
Reference Ranges ◽  
Serum Samples ◽  
Late Night ◽  
Liquid Chromatography Tandem Mass ◽  
Adrenal Masses ◽  
Suppression Test ◽  
The Individual

Abstract Biochemical function of adrenal masses is currently based on 1mg post-overnight dexamethasone suppression test (pDST). Several approaches are recently developed, in order to reduce false positive/negative samples, only in retrospective series. They are based on the correlation of some different parameters, i.e. late-night salivary cortisol (LNSC) vs serum and salivary cortisol pDST; LNSC vs serum and salivary cortisol and serum dexamethasone pDST; LNSC and cortisone vs serum cortisol and salivary cortisol and cortisone pDST. Although these findings offer a better diagnostic performance, several conditions are still disappointed. No information is traceable about the harvest time of diurnal salivary and serum samples and no study include neither the levels of salivary nor urinary dexamethasone pDST. Aim of our study is to combine all these strategies in order to avoid the underestimated biases and obtain more precise information about the true “cortisol condition” of the patients. To reach this purpose we assess both cortisol and dexamethasone concentrations in several samples: saliva at 11PM before the drug administration, diurnal saliva and serum at 8AM and also the urine collection from 11PM to 8AM. Analytes levels are measured using a validated liquid chromatography-tandem mass spectrometry method. In this study we included 20 subjects without morphological adrenal alteration (MRI assessment), dyslipidemia, hypertension and impaired glucose tolerance (healthy controls) and 20 patients with adrenal incidentaloma showing different cortisol levels ranging from normal to ACTH-independent hypercortisolism. In both series, LNSC were similar to salivary cortisol pDST, even if they were greater in the patients with adrenal incidentalomas and subclinical cortisol secretion. Serum dexamethasone levels were in reference ranges, while salivary and urinary dexamethasone found in these matrices require additional sample numbers in order to establish appropriate cut-offs. Our preliminary results suggest that the combination of these findings could represent an improvement to assess the individual cortisol status.

scholarly journals Paritaprevir and Ritonavir Liver Concentrations in Rats as Assessed by Different Liver Sampling Techniques

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Charles S. Venuto ◽  
Marianthi Markatou ◽  
Yvonne Woolwine-Cunningham ◽  
Rosemary Furlage ◽  
Andrew J. Ocque ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Needle Aspiration ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Time Curve ◽  
Tissue Samples ◽  
Drug Concentrations ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass

ABSTRACT The liver is crucial to pharmacology, yet substantial knowledge gaps exist in the understanding of its basic pharmacologic processes. An improved understanding for humans requires reliable and reproducible liver sampling methods. We compared liver concentrations of paritaprevir and ritonavir in rats by using samples collected by fine-needle aspiration (FNA), core needle biopsy (CNB), and surgical resection. Thirteen Sprague-Dawley rats were evaluated, nine of which received paritaprevir/ritonavir at 30/20 mg/kg of body weight by oral gavage daily for 4 or 5 days. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry on samples collected via FNA (21G needle) with 1, 3, or 5 passes (FNA1, FNA3, and FNA5); via CNB (16G needle); and via surgical resection. Drug concentrations in plasma were also assessed. Analyses included noncompartmental pharmacokinetic analysis and use of Bland-Altman techniques. All liver tissue samples had higher paritaprevir and ritonavir concentrations than those in plasma. Resected samples, considered the benchmark measure, resulted in estimations of the highest values for the pharmacokinetic parameters of exposure (maximum concentration of drug in serum [C max] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) for paritaprevir and ritonavir. Bland-Altman analyses showed that the best agreement occurred between tissue resection and CNB, with 15% bias, followed by FNA3 and FNA5, with 18% bias, and FNA1 and FNA3, with a 22% bias for paritaprevir. Paritaprevir and ritonavir are highly concentrated in rat liver. Further research is needed to validate FNA sampling for humans, with the possible derivation and application of correction factors for drug concentration measurements.

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