scholarly journals Critical Drug Loss Induced by Silicone and Polyurethane Implantable Catheters in a Simulated Infusion Setup with Three Model Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1709
Author(s):  
Nicolas Tokhadzé ◽  
Philip Chennell ◽  
Bruno Pereira ◽  
Bénédicte Mailhot-Jensen ◽  
Valérie Sautou
Keyword(s):  
Liquid Chromatography ◽  
Ir Spectroscopy ◽  
High Drug ◽  
Drug Concentrations ◽  
Drug Loss ◽  
Surface Potential Measurements ◽  
Clinical Consequences ◽  
Polyurethane Catheter ◽  
Materials Used ◽  
Polyurethane Catheters

Silicone and polyurethane are biocompatible materials used for the manufacture of implantable catheters, but are known to induce drug loss by sorption, causing potentially important clinical consequences. Despite this, their impact on the drugs infused through them is rarely studied, or they are studied individually and not part of a complete infusion setup. The aim of this work was to experimentally investigate the drug loss that these devices can cause, on their own and within a complete infusion setup. Paracetamol, diazepam, and insulin were chosen as models to assess drug sorption. Four commonly used silicone and polyurethane catheters were studied independently and as part of two different setups composed of a syringe, an extension set, and silicone or polyurethane implantable catheter. Simulated infusion through the catheter alone or through the complete setup were tested, at flowrates of 1 mL/h and 10 mL/h. Drug concentrations were monitored by liquid chromatography, and the silicone and polyurethane materials were characterized by ATR-IR spectroscopy and Zeta surface potential measurements. The losses observed with the complete setups followed the same trend as the losses induced individually by the most sorptive device of the setup. With the complete setups, no loss of paracetamol was observed, but diazepam and insulin maximum losses were respectively of 96.4 ± 0.9% and 54.0 ± 5.6%, when using a polyurethane catheter. Overall, catheters were shown to be the cause of some extremely high drug losses that could not be countered by optimizing the extension set in the setup.

scholarly journals Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1379 ◽  
Author(s):  
Sarah Stewart ◽  
Juan Domínguez-Robles ◽  
Ryan Donnelly ◽  
Eneko Larrañeta
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Patient Compliance ◽  
Oral Delivery ◽  
Oral Route ◽  
Clinical Applications ◽  
Drug Concentrations ◽  
Effective Delivery ◽  
Materials Used ◽  
Drug Delivery Devices

The oral route is a popular and convenient means of drug delivery. However, despite its advantages, it also has challenges. Many drugs are not suitable for oral delivery due to: first pass metabolism; less than ideal properties; and side-effects of treatment. Additionally, oral delivery relies heavily on patient compliance. Implantable drug delivery devices are an alternative system that can achieve effective delivery with lower drug concentrations, and as a result, minimise side-effects whilst increasing patient compliance. This article gives an overview of classification of these drug delivery devices; the mechanism of drug release; the materials used for manufacture; the various methods of manufacture; and examples of clinical applications of implantable drug delivery devices.

scholarly journals Paradoxical Effect of Caspofungin: Reduced Activity against Candida albicans at High Drug Concentrations

2004 ◽  
Vol 48 (9) ◽  
pp. 3407-3411 ◽  
Author(s):  
David A. Stevens ◽  
Marife Espiritu ◽  
Rachana Parmar
Keyword(s):  
Candida Albicans ◽  
Resistance Mechanisms ◽  
Paradoxical Effect ◽  
Fungal Cell ◽  
High Drug ◽  
Minimum Fungicidal Concentration ◽  
Drug Concentrations ◽  
High Concentrations ◽  
Glucan Synthesis

ABSTRACT Resistance problems with caspofungin, an echinocandin inhibitor of fungal cell wall glucan synthesis, have been rare. We noted paradoxical turbid growth of Candida albicans isolates in broth in some high (supra-MIC) concentrations. Among isolates submitted for susceptibility testing and screened at drug concentrations up to 12.5 μg/ml, the frequency was 16%. Analysis of the turbid growth indicated slowing of growth in the presence of drug but with numbers of CFU up to 72% those of drug-free controls. Clearing of growth again by the highest drug concentrations produced a quadriphasic pattern in a tube dilution series. Cells growing at high drug concentrations were not resistant on retesting but showed the paradoxical effect of the parent. Among a selected series of isolates tested at concentrations up to 50 μg/ml, an additional 53% showed a “mini-paradoxical effect”: no turbid growth but incomplete killing at high concentrations (supra-minimum fungicidal concentration). These effects were reproducible; medium dependent in extent; noted in macro- and microdilution, in the presence or absence of serum, and on agar containing drug (but not when drug concentrations were not constant, as in agar diffusion); not seen with other echinocandins and less commonly in other Candida species; and not due to destruction of drug in tubes showing the effect. Cooperative enhancement of inhibition by a second drug could eradicate the effect. We postulate that high drug concentrations derepress or activate resistance mechanisms. The abilities of subpopulations to survive at high drug concentrations could have in vivo consequences.

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.

Monitoring drug concentrations in a case of combined overdosage with primidone and methsuximide.

1976 ◽  
Vol 22 (6) ◽  
pp. 915-921 ◽  
Author(s):  
G F Johnson ◽  
C J Least ◽  
J W Serum ◽  
E B Solow ◽  
H M Solomon
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Liquid Chromatography ◽  
Gas Chromatography Mass Spectrometry ◽  
Gas Liquid Chromatography ◽  
Therapeutic Decision ◽  
Serum Samples ◽  
Monitoring Drug ◽  
Drug Concentrations

Abstract We describe a case of fatal overdosage with primidone and methsuximide. During the early phase of the patient's hospital course we found concentrations of methsuximide, N-desmethylmethsuximide, and primidone in serum that far exceeded the usual therapeutic concentrations, as determined by gas-liquid chromatography. Determination of N-desmethylmethsuximide in peritoneal fluid demonstrated concentrations comparable to those in serum. This led to the therapeutic decision to manage the patient by dialysis. Subsequently, serum samples collected during the course of hospitalization were analyzed quantitatively by gas-liquid chromatography for methsuximide, N-desmethylmethsuximide, primidone, phenobarbital, and diphenylhydantoin. Selected serum specimens were also analyzed by gas chromatography-mass spectrometry, and N-methyl-2-hydroxymethyl-2-phenylsuccinimide, a metabolite of methsuximide not previously described in human serum, was identified by analysis of its mass spectrum.

Compatibility of treprostinil sodium and dopamine hydrochloride during simulated Y-site administration

2020 ◽  
Vol 77 (8) ◽  
pp. 649-657
Author(s):  
Anna Bustin ◽  
E Zachary Ramsey ◽  
Brian D Hanna ◽  
Gagan Kaushal
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Chemical Stability ◽  
High Performance ◽  
Stability Testing ◽  
Visual Examination ◽  
Stability Indicating ◽  
Drug Concentrations ◽  
Dopamine Hydrochloride ◽  
Physical And Chemical

Abstract Purpose To evaluate the physical and chemical compatibilities of treprostinil sodium and dopamine hydrochloride. Methods Treprostinil sodium (4,000, 76,000, and 500,000 ng/mL) were mixed with dopamine hydrochloride (0.6, 3.2, 6, and 40 mg/mL). Samples were obtained at hours 0, 1, 2, and 4 for physical compatibility and chemical stability testing. Physical compatibility was assessed by visual examination and measurements of turbidity and pH. Drug concentrations were assessed using stability-indicating liquid chromatography mass spectrophotometry (LCMS) for treprostinil sodium and stability-indicating high-performance liquid chromatography (HPLC) for dopamine hydrochloride. Results Treprostinil sodium 4,000 and 76,000 ng/mL, when mixed with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL, were stable for 4 hours. Treprostinil sodium 500,000 ng/mL was stable when mixed with dopamine hydrochloride 0.6 mg/mL for 4 hours, but when mixed with dopamine hydrochloride 3.2, 6, and 40 mg/mL, significant precipitation was seen. Conclusion Treprostinil sodium 4,000 and 76,000 ng/mL were stable for 4 hours during simulated Y-site coadministration with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL. Treprostinil sodium 500,000 ng/mL is stable when mixed with dopamine hydrochloride 0.6 mg/mL.

scholarly journals Clinical Evaluation of a Dried Blood Spot Assay for Atazanavir

2010 ◽  
Vol 54 (10) ◽  
pp. 4124-4128 ◽  
Author(s):  
Trevor Van Schooneveld ◽  
Susan Swindells ◽  
Sarah R. Nelson ◽  
Brian L. Robbins ◽  
Ryan Moore ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Plasma Concentrations ◽  
Reversed Phase ◽  
Hiv Protease ◽  
Dried Blood Spot ◽  
Hiv Protease Inhibitors ◽  
Hiv Rna ◽  
Drug Concentrations ◽  
Blood Spot

ABSTRACT Current procedures for obtaining and measuring plasma concentrations of HIV protease inhibitors (PIs) are technically challenging. Dried blood spot (DBS) assays offer a way to overcome many of the obstacles. We sought to develop a DBS assay for quantitation of the PI atazanavir (ATV) and to compare this method with a previously validated plasma assay. We prospectively enrolled 48 patients with well-controlled HIV disease who had been on ATV for at least 7 days. ATV was quantified from plasma by use of high-performance liquid chromatography (HPLC). A reversed-phase ultrahigh-performance liquid chromatography (UPLC) assay was utilized for DBS samples. The concentrations of ATV quantified in a DBS matrix showed very strong agreement with those measured in plasma (r 2 = 0.988). The mean difference in ATV concentration between the two methods was −10.8% (95% confidence interval [95% CI], −7.65% to −13.95%), indicating that the DBS method has a slight negative bias. A majority (97.8%) of the differences in concentration between the two assays fell within ±2 standard deviations. ATV concentrations were lower in subjects who had detectable HIV RNA in plasma (mean, 543 ng/ml) than in those with HIV RNA of <50 copies/ml (mean, 1,582 ng/ml) (P = 0.03, Wilcoxon rank-sum test). In conclusion, our study demonstrated that ATV quantitation in a DBS matrix is feasible and accurate. DBS use offers a convenient alternative for measuring plasma concentrations of ATV and may have utility in monitoring of drug concentrations in clinical practice and in future studies.

Simultaneous quantitation of quinidine, procainamide, and N-acetylprocainamide in serum by gas-liquid chromatography with a nitrogen-phosphorus selective detector.

1982 ◽  
Vol 28 (5) ◽  
pp. 1187-1190 ◽  
Author(s):  
K M Kessler ◽  
P Ho-Tung ◽  
B Steele ◽  
J Silver ◽  
A Pickoff ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Clinical Application ◽  
Gas Liquid Chromatography ◽  
Drug Concentrations ◽  
Selective Detector ◽  
Nitrogen Phosphorus

Abstract We describe a single-run method for quantitating quinidine, procainamide, and N-acetylprocainamide, involving gas-liquid chromatography with a nitrogen-phosphorus selective detector. Within-run precision (CV) was 3% (x = 2 mg/L, n = 20), 6.9% (x = 4 mg/L, n = 10), and 1.5% (x = 8 mg/L, n = 8) for quinidine; 7.7% (x = 4 mg/L, n = 14), 1.6% (x = 8 mg/L, n = 16), and 2.3% (x = 12 mg/L, n = 12) for procainamide; and 6.3% (x = 5 mg/L, n = 6), 3.6% (x = 10 mg/L, n = 20), and 4.0% (x = 20 mg/L, n = 10) for N-acetylprocainamide.l Between-run precision was 3.0%(x = 2 mg/L, n = 20), 7.0% (x = 4 mg/L, n = 9), and 2.8% (x = 8 mg/L, n = 9) for quinidine; 4.7% (x = 4 mg/L, n = 10). 3.3% (x = 8 mg/L, n = 20), and 1.9% (x = 12 mg/L, n = 10) for procainamide; and 9.3% (x = 5 mg/L, n = 6), 4.3% (x = 10 mg/L, n = 20), and 3.8% (x = 20 mg/L, n = 10) for N-acetylprocainamide. Tube stoppers that contain a rubber plasticizer interfere with the technique. Clinical application and correlation with drug concentrations by this technique are discussed.

Acetaminophen Metabolism in Man, as Determined by High-Resolution Liquid Chromatography

1974 ◽  
Vol 20 (8) ◽  
pp. 1086-1096 ◽  
Author(s):  
J E Mrochek ◽  
S Katz ◽  
W H Christie ◽  
S R Dinsmore
Keyword(s):  
Liquid Chromatography ◽  
High Resolution ◽  
Sample Pretreatment ◽  
Free Drug ◽  
Serum Concentrations ◽  
Clinically Normal ◽  
Drug Concentrations ◽  
Excretion Rates ◽  
The Individual ◽  
Normal Men

Abstract Acetaminophen is a commonly used analgesic, available without prescription. Several of its metabolites have heretofore been isolated from physiologic fluids and analytically characterized. In general, the separation methods are complicated, usually requiring extensive sample pretreatment, and do not measure the individual conjugated metabolites. High-resolution anionexchange separation of urinary samples from subjects receiving acetaminophen reveals eight chromatographic peaks, representing seven metabolites and the free drug itself. Metabolites separated include 2-methoxyacetaminophen, its glucuronide and sulfate conjugates, the sulfate conjugate of 2-hydroxyacetaminophen, the glucuronide and sulfate conjugates of acetaminophen, S-(5-acetamido-2-hydroxyphenyl)cysteine, and S-(5-acetamido-2-glucuronosidophenyl)cysteine. Urinary and serum concentrations of the drug and its seven metabolites were determined by high-resolution liquid chromatography as a function of time after two clinically normal men ingested 1950 mg of the drug. Concentrations in urine and serum are compared, and estimated urinary excretion rates are reported for all metabolites except S-(5-acetamido-2-hydroxyphenyl)cysteine. Serum concentrations of the glucuronide were higher than concentrations of the free drug 2 h after the drug was ingested, indicating that solvent-extraction procedures for serum will yield low estimates of total drug unless hydrolysis precedes the extraction step.

scholarly journals Determination of Bedaquiline in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry

2015 ◽  
Vol 59 (9) ◽  
pp. 5675-5680 ◽  
Author(s):  
Jan-Willem C. Alffenaar ◽  
Mathieu Bolhuis ◽  
Kai van Hateren ◽  
Marieke Sturkenboom ◽  
Onno Akkerman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Human Serum ◽  
Internal Standard ◽  
Pharmacokinetic Data ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Drug Concentrations ◽  
Liquid Chromatography Tandem Mass

ABSTRACTBedaquiline, a diarylquinoline for the treatment of multidrug-resistant tuberculosis (TB), relies on exposure-dependent killing. As data on drug exposure in specific populations are scarce, pharmacokinetic studies may be of interest. No simple and robust validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been reported to date. Therefore, a new method using a quadrupole mass spectrometer was developed for analysis of bedaquiline andN-monodesmethyl bedaquiline (M2) in human serum, using deuterated bedaquiline as the internal standard. The calibration curve was linear over a range of 0.05 (lower limit of quantification [LLOQ]) to 6.00 mg/liter for both bedaquiline and M2, with correlation coefficient values of 0.997 and 0.999, respectively. The calculated accuracy ranged from 1.9% to 13.6% for bedaquiline and 2.9% to 8.5% for M2. Within-run precision ranged from 3.0% to 7.2% for bedaquiline and 3.1% to 5.2% for M2, and between-run precision ranged from 0.0% to 4.3% for bedaquiline and 0.0% to 4.6% for M2. Evaluation of serum concentrations in a patient receiving bedaquiline showed high levels at the end of treatment, reflecting accumulation of the drug. More observational pharmacokinetic data are needed to relate altered drug concentrations to clinical outcome or adverse drug effects. A simple LC-MS/MS method to quantify bedaquiline and M2 levels in human serum using a deuterated internal standard has been validated. This method can be used in clinical studies and daily practice.

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