Determination of the chlorofluorocarbon substitute 1,1,1,2-tetrafluoroethane (HFA-134a) in human and animal blood using gas chromatography with headspace analysis

Cooper, Katherine M.; Chang, Shaw F.; Harrison, Lester I.

doi:10.1016/0378-4347(95)00013-9

Cited by 6 publications

(2 citation statements)

References 23 publications

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“…Although our data are limited, these HFA-134a levels coupled with the results of other studies [16,22,23] provide preliminary evidence for the prompt pulmonary absorption and rapid removal from the blood of HFA-134a. This pharmacokinetic behavior is similar to that of CFC propellants 11 and 12 used in current CFC formulations [24,25].…”

Section: Discussionsupporting

confidence: 63%

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Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler

Donnell¹,

Harrison²,

Ward

et al. 1995

Eur J Clin Pharmacol

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The acute safety of the alternative chlorofluorocarbon-free (CFC-free) propellant HFA-134a from a pressurized metered-dose inhaler (MDI) was assessed in 12 healthy male subjects according to a double-blind, randomized, crossover design. On each of three consecutive days, cumulative doses of 1,2,4,8 and 16 inhalations were administered 30 min apart from one of three MDIs. The three MDIs contained either the HFA-134a CFC-free system without drug (HFA-Placebo), the CFC-free system with salbutamol sulphate (HFA-Salbutamol), or a conventional CFC propellant mixture without drug (CFC-Placebo). Pulmonary function (FEV1, FEF25-75%), cardiovascular performance (heart rate and blood pressure), objective tremor measurements and serum potassium were measured after each incremental dose. Similar responses for pulmonary function, cardiovascular performance, tremor and serum potassium were observed between the HFA-Placebo and CFC-Placebo groups. No statistically significant difference was seen in change from baseline of any parameter between the two propellant systems. The administration of HFA-Salbutamol produced statistically significant dose-related increases in heart rate, systolic blood pressure and tremor and a significant dose-related decrease in serum potassium; these responses were expected based on cumulative doses of active drug. Blood samples for HFA-134a analysis were collected to measure systemic absorption of this propellant. Levels of HFA-134a between 200 and 700 ng.ml-1 were detected in all subjects given the CFC-free system. This study shows that acute inhalation of HFA-134a in a CFC-free system is as safe as a CFC propellant system. Salbutamol sulphate in the CFC-free system can be delivered in a dose-linear fashion, without any noticeable change in the safety profile of active drug.

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Section: Discussionsupporting

confidence: 63%

“…HFA-134a levels in whole blood were determined using headspace capillary gas chromatography [16]. The calibration range was extended to 806 rig-ml 1 after preliminary results indicated that levels greater than 493 ng' m1-1 were being observed.…”

Section: Study Populationmentioning

confidence: 99%

Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler

Donnell¹,

Harrison²,

Ward

et al. 1995

Eur J Clin Pharmacol

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A Validated Method for the Quantitation of 1,1-Difluoroethane Using a Gas in Equilibrium Method of Calibration

Avella¹,

Lehrer²,

Zito³

2008

Journal of Analytical Toxicology

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1,1-Difluoroethane (DFE), also known as Freon 152A, is a member of a class of compounds known as halogenated hydrocarbons. A number of these compounds have gained notoriety because of their ability to induce rapid onset of intoxication after inhalation exposure. Abuse of DFE has necessitated development of methods for its detection and quantitation in postmortem and human performance specimens. Furthermore, methodologies applicable to research studies are required as there have been limited toxicokinetic and toxicodynamic reports published on DFE. This paper describes a method for the quantitation of DFE using a gas chromatography-flame-ionization headspace technique that employs solventless standards for calibration. Two calibration curves using 0.5 mL whole blood calibrators which ranged from A: 0.225-1.350 to B: 9.0-180.0 mg/L were developed. These were evaluated for linearity (0.9992 and 0.9995), limit of detection of 0.018 mg/L, limit of quantitation of 0.099 mg/L (recovery 111.9%, CV 9.92%), and upper limit of linearity of 27,000.0 mg/L. Combined curve recovery results of a 98.0 mg/L DFE control that was prepared using an alternate technique was 102.2% with CV of 3.09%. No matrix interference was observed in DFE enriched blood, urine or brain specimens nor did analysis of variance detect any significant differences (alpha = 0.01) in the area under the curve of blood, urine or brain specimens at three identical DFE concentrations. The method is suitable for use in forensic laboratories because validation was performed on instrumentation routinely used in forensic labs and due to the ease with which the calibration range can be adjusted. Perhaps more importantly it is also useful for research oriented studies because the removal of solvent from standard preparation eliminates the possibility for solvent induced changes to the gas/liquid partitioning of DFE or chromatographic interference due to the presence of solvent in specimens.

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Systemic Concentrations of Salbutamol and HFA-134a After Inhalation of Salbutamol Sulfate in a Chlorofluorocarbon-Free System

Harrison¹,

Cline²,

Wells³

et al. 1996

Therapeutic Drug Monitoring

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The objective of this study was to determine if salbutamol was absorbed from a new salbutamol sulfate chlorofluorocarbon (CFC)-free metered-dose inhaler (MDI). Measurement of HFA-134a, the CFC-free propellant, was included to provide proof of delivery of this MDI. Eight healthy men received two inhalations (90 micrograms salbutamol base equivalents per inhalation ex adapter) from the CFC-free inhaler (MDI A) in period 1 and from a reference CFC inhaler (MDI V) in period 2. Eight postdose samples were collected for the determination of salbutamol serum levels over a 4-h period. Salbutamol levels were not quantifiable in most samples. Four subjects given MDI A and two given MDI V had a few transient salbutamol levels, which occurred in the first hour after dosing, within a narrow range of 1-2 ng/ml and close to the lower limit of detection (1 ng/ml). No pharmacokinetic analyses were possible. Blood samples were also collected after MDI A for propellant quantitation. HFA-134a levels were seen in all subjects, verifying absorption. We conclude that the transient salbutamol serum levels can be attributed to the two-inhalation dose and not to either propellant system.

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Determination of the chlorofluorocarbon substitute 1,1,1,2-tetrafluoroethane (HFA-134a) in human and animal blood using gas chromatography with headspace analysis

Cited by 6 publications

References 23 publications

Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler

Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler

A Validated Method for the Quantitation of 1,1-Difluoroethane Using a Gas in Equilibrium Method of Calibration

Systemic Concentrations of Salbutamol and HFA-134a After Inhalation of Salbutamol Sulfate in a Chlorofluorocarbon-Free System

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