Rapid gas—liquid chromatographic estimation of doxapram in plasma

Robson, R. H.; Prescott, L. F.

doi:10.1016/s0378-4347(00)81800-9

Cited by 20 publications

(10 citation statements)

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“…Despite these applications, little is known of the pharmacokinetic properties of doxapram. A gas-liquid chromatographic assay for the drug and one of its major metabolites has recently been developed (Robson & Prescott, 1977) and in this report we describe studies on the disposition and pharmacokinetics of doxapram in patients with respiratory failure and healthy volunteers given oral and intravenous doxapram.…”

Section: Introduction Methodsmentioning

confidence: 99%

“…Doxapram was estimated in plasma and urine by gas chromatography using naftidrofuryl as an internal standard and a nitrogen sensitive flame ionization detector (Robson & Prescott, 1977). A primary metabolite of doxapram, produced by keto-oxidation of the morpholine ring (I-ethyl4-[2-(morpholin-2-one)-ethyll-3,3-diphenyl-2-pyrrolidinone) (AHR 5955; Figure 1), was also estimated in plasma in some studies.…”

Section: Estimation Ofdoxaprammentioning

confidence: 99%

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A pharmacokinetic study of doxapram in patients and volunteers.

Robson¹,

Prescott²

1979

Brit J Clinical Pharma

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1. Following intravenous bolus injections or brief infusions in healthy volunteers, plasma concentrations of doxapram declined in a multi‐ exponential fashion. The mean half‐life from 4‐12 h was 3.4 h (range 2.4‐4.1h), the mean apparent volume of distribution was 1.5 1 kg‐1 and the whole body clearance was 370 ml min‐1. 2. Enteric‐coated capsules of doxapram base were absorbed rapidly after an initial delay, and the systemic availability was about 60%. 3. Doxapram is extensively metabolized and less than 5% of an i.v. dose was excreted unchanged in the urine in 24 h. A metabolite (AHR 5955) was present in plasma in amounts comparable to the parent compound and had a similar half‐life. 4. The disposition of doxapram appears to be similar in healthy volunteers and patients with respiratory failure. 5. The previously held belief that plasma concentrations fall rapidly when an infusion is stopped is only true following short duration infusions. The pharmacokinetic properties of doxapram are such that steady‐state plasma concentrations will not be achieved for many hours with the recommended constant rate infusion regime.

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Section: Introduction Methodsmentioning

confidence: 99%

Section: Estimation Ofdoxaprammentioning

confidence: 99%

A pharmacokinetic study of doxapram in patients and volunteers.

Robson¹,

Prescott²

1979

Brit J Clinical Pharma

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“…Several methods were published for the determination of doxapram in different biological matrices, such as liquid chromatography with ultraviolet detector (LC-UV) [6,7] and gas chromatography (GC) with flame ionization detector (FID) [8,9], nitrogen-phosphorus detector (NPD) [10] or mass spectrometry (MS) [10,11]. Most of these reports describe assays for quantification of doxapram in plasma involving alkaline extraction of the drug and gas chromatography [8][9][10][11], 1-3 lL were injected into the gas column for analysis, with a limit of quantitation (LOQ) of 10-50 ng mL -1 using 50-200 lL plasma, in contrast to the 2 mL plasma needed in [9].…”

Section: Introductionmentioning

confidence: 99%

“…Most of these reports describe assays for quantification of doxapram in plasma involving alkaline extraction of the drug and gas chromatography [8][9][10][11], 1-3 lL were injected into the gas column for analysis, with a limit of quantitation (LOQ) of 10-50 ng mL -1 using 50-200 lL plasma, in contrast to the 2 mL plasma needed in [9]. Compared to GC, the LC assay described in [6,7] is simple, and requires small plasma samples.…”

Section: Introductionmentioning

confidence: 99%

Determination of Doxapram Hydrochloride in Rabbit Plasma by LC-MS-MS and Its Application

Lin

et al. 2011

Chromatographia

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A sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS-MS) method for determination of doxapram hydrochloride in rabbit plasma was developed. After addition of urapidil hydrochloride as internal standard (IS), protein precipitation by 10% trichloroacetic acid in methanol (w/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm 9 50 mm, 3.5 lm) column with acetonitrile-water as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used for quantification using target fragment ions m/z 378.9 ? 291.8 for doxapram hydrochloride and m/z 387.9 ? 204.6 for the IS. Calibration plots were linear over the range of 2-1000 ng mL -1 for doxapram hydrochloride in plasma. Lower limit of quantitation (LLOQ) for doxapram hydrochloride was 2 ng mL -1 . Mean recovery of doxapram hydrochloride from plasma was in the range 83.7-91.5%. RSD of intra-day and inter-day precision were less than 9%, respectively. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of doxapram hydrochloride in rabbit plasma.

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“…The blood was collected onto heparin, centrifuged and the plasma frozen. The plasma was subsequently assayed for doxapram using a gas chromatographic method (Robson & Prescott, 1977).…”

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confidence: 99%