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G J Sewell

Publications and source records attributed to G J Sewell.

17 recordsLinked to original sources
PubMed1996

Novel liquid chromatographic assay for the low-level determination of apomorphine in plasma.

A novel HPLC assay which is rapid, reproducible and sensitive has been developed for the analysis of apomorphine in plasma. The assay incorporates boldine as an internal standard, and uses solid-phase extraction on C18 mini-columns for sample clean-up and concentration, so enabling quantitation of apomorphine at 500 pg/ml using fluorescence detection (lambda(ex) 270 nm, lambda(em) 450 nm). The HPLC assay comprised a 25 cm-long Techopak C18 column and a mobile phase of (0.25 M sodium dihydrogen phosphate plus 0.25% heptane sulphonic acid, to pH 3.3 with orthophosphoric acid) containing 30% (v/v) methanol and 0.003% (w/v) EDTA, run at a flow-rate of 1.5 ml/min. Calibration plots prepared in plasma were linear over the range 1-30 ng/ml, (limit of quantitation (LOQ) = 490 pg/ml) with R.S.D. of 0.05% and R.E. of 5.0% at the level of 1 ng/ml. Preliminary pharmacokinetic data from two patients given apomorphine by 12 h subcutaneous infusion (patient A dose = 35 mg and patient B dose = 141 mg) showed apomorphine elimination from plasma to fit a two-compartment model, with initial half-lives of 8.2 and 46.6 min, elimination half-lives of 76.4 and 166.5 min and area under the plasma concentration-time curve (AUC) values of 236 and 405 ng h/ml, respectively.

Antioxidants↗
PubMed1995

Practical guides. II: Hospital pharmacy quality control services.

This article briefly reviews the evolution, scope and operation of hospital quality control (QC) services. Recent initiatives and developments are considered alongside the traditional 'core' QC/quality assurance (QA) work. Important new areas of work which could benefit from QC involvement are also discussed.

Guidelines as Topic↗
PubMed1994

Improved LC assay for the determination of mitozantrone in plasma: analytical considerations.

Preliminary method development studies on mitozantrone (MTZ) revealed a number of characteristics which were found to be important in the analysis of patient samples for pharmacokinetic studies. MTZ rapidly bound to glass, particularly at low concentrations (< 10 ng ml-1), necessitating the use of silanized glassware or polypropylene tubes for the handling of all solutions containing MTZ. MTZ was also found to react with two commonly-used antioxidants; sodium metabisulphite and EDTA. However, solutions containing MTZ were found to be stabilized by the addition of ascorbic acid (0.5% w/v). In the absence of ascorbic acid, MTZ underwent rapid, biphasic degradation in plasma at 24 and 37 degrees C, with terminal half-lives of approximately 70 h. Ascorbic acid (0.5% 2/v) was found to stabilize plasma samples containing MTZ throughout work-up procedures and during frozen storage. The addition of ascorbic acid to the sample collection vial was also necessary to prevent MTZ degradation in the eluting solvent of the solid-phase extraction system. Another important consideration was the requirement for an equilibration period of > 5 min after the addition of ametantrone (AM) internal standard to plasma samples. This was essential, since the slope of the calibration plot obtained using non-equilibrated plasma was approximately 30% of that obtained for calibration plots using equilibrated plasma, and would result in erroneous determination of MTZ plasma concentrations. The fully developed assay was rapid, precise and sensitive (relative errors at 1 ng ml-1 = 2.3%). MTZ concentrations determined using the LC method described in this report correlated well with an independently developed ELISA technique (r = 0.995, n = 20).

Antineoplastic Agents↗
PubMed1994

Stability studies on admixtures of 5-fluorouracil with carboplatin and 5-fluorouracil with heparin for administration in continuous infusion regimens.

The therapeutic index of several anticancer agents may be improved by replacing rapid infusion/bolus injection schedules with prolonged continuous infusion regimens. Admixtures of 5-fluorouracil (5FU) with carboplatin and 5FU with heparin were subjected to stability studies to establish the feasibility of administering these infusions on an in-patient and out-patient basis, respectively. In the first study the stability of carboplatin was determined in an admixture of carboplatin and 5FU for neoadjuvant treatment of in-patients with oesophageal carcinoma by 5-day infusion. A previous study had reported significant carboplatin degradation in 5FU/carboplatin admixtures. Our results were consistent with this study and demonstrated that under ward conditions (25 degrees C) carboplatin also degraded (16% in 24 h) in dilute admixtures with 5FU. However, the addition of a citric acid buffer, which reduced infusion pH from 8.65 to 6.5, increased the stability of carboplatin (4.8% degradation in 24 h), without compromising 5FU solubility or stability. In a second study, the stability of an infusion containing 5FU and heparin was determined. Prolonged continuous infusion is routinely used for adjuvant treatment of colorectal carcinoma but episodes of thromboses and occlusion of the central venous catheter have been associated with this treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboplatin↗
PubMed1991

The stability of carboplatin, diamorphine, 5-fluorouracil and mitozantrone infusions in an ambulatory pump under storage and prolonged 'in-use' conditions.

Drug infusions can be exposed for prolonged periods to 'in-use' conditions where the temperature of an infusion in a holster-worn infusion pump may reach 37 degrees C. In this study, the stability of three cytotoxic drug infusions (carboplatin, 5-fluorouracil and mitozantrone) and one analgesic infusion (diamorphine HCl) was determined in Parker Micropump medication reservoirs under refrigerated storage and prolonged in-use conditions. The stability of the three cytotoxic drug infusions was unaffected by 14 days storage at either 4 or 37 degrees C. The diamorphine HCl infusion was stable over 14 days storage at 4 degrees C but under in-use conditions at 37 degrees C, drug degradation became significant (greater than 5%) if storage exceeded 7 days.

Carboplatin↗
PubMed1990

General practice theophylline audit in the Exeter Health District.

The serum theophylline concentration was determined in 150 asthmatic patients who received treatment from General Practitioners in the Exeter Health District. The serum theophylline concentration was below the therapeutic range in 75% of the patients evaluated. There was no correlation between serum concentration and daily dose, even when the latter was calculated with respect to bodyweight or body surface area. It was concluded that a theophylline Therapeutic Drug Monitoring (TDM) service should be available for general practice patients.

Asthma↗
PubMed1988

Qualitative studies on alpha-interferon-2b in prolonged continuous infusion regimes using gradient elution high-performance liquid chromatography.

The treatment of home-based cancer patients with continuous infusion chemotherapy requires that complete courses of medication in pre-filled syringes are provided on an out-patient basis. The infusion must remain stable prior to use during refrigerated storage (up to 14 days) and during infusion from holster-worn ambulatory infusion pumps where the temperature of the infusion can reach 37 degrees C. In this study, polypropylene syringes containing interferon alpha-2b infusion (3 mega units in 6 ml) were stored at 4 degrees C. The infusion was analysed during storage by a qualitative gradient-elution high-performance liquid chromatography procedure. Over 14 days storage at 4 degrees C or 24 h storage at 37 degrees C, chromatographic changes occurred indicating interconversion between interferon monomers and possibly oligomer formation. Until further studies are completed we consider interferon alpha-2b unsuitable for inclusion in our home oncology programme.

Chromatography, High Pressure Liquid↗
PubMed1988

The formulation and stability of a unit-dose oral vitamin K1 preparation.

A unit-dose oral vitamin K1 solution (1 mg ml-1) was developed for administration to neonates as prophylaxis against early haemorrhagic disease of the new-born. Previously, a multidose oral-drop solution was prepared from sterile ampoules of vitamin K1 injection (10 mg ml-1). The unit-dose preparation enabled accurate and convenient dose delivery and was more economical than the multidose solution. Furthermore, the preparation of sterile, single-dose units enabled the elimination of potentially harmful preservatives from the formulation. The unit-dose preparation was shown to be stable for 6 months under refrigerated storage conditions.

Chromatography, High Pressure Liquid↗
PubMed1987

The stability of carboplatin in ambulatory continuous infusion regimes.

Several anti-cancer agents are administered by continuous infusion in an attempt to improve the therapeutic index obtained with solid tumours. In Exeter this approach, combined with the use of ambulatory infusion pumps, forms the basis of a home oncology programme in which a complete course of medication in pre-filled syringes is supplied on an out-patient basis. It is essential to ensure that the drug remains stable during storage prior to use and also during infusion where the temperature of the drug solution in a holster-worn ambulatory pump can reach 37 degrees C. In this study the stability of a carboplatin infusion (20 mg in 2 ml) in pre-filled syringes under storage and in-use conditions was determined using a stability-indicating HPLC assay. There was no loss of carboplatin from pre-filled syringes stored at 4 degrees C for 5 days. At 37 degrees C, the loss of carboplatin was 3.1% over 24 h.

Antineoplastic Agents↗
PubMed1986

Analysis of hospital-formulated oral liquid preparations by second derivative ultraviolet spectroscopy.

Second derivative ultraviolet spectrophotometric methods have been devised for the analysis of hospital-formulated oral liquid preparations. These rapid techniques are useful in the routine quality control of oral liquid formulations where direct spectrophotometric determination of the drug analyte is precluded by interference from formulation excipients and colouring agents. This report describes examples in which the active principles of a dipipanone mixture, a methadone mixture and an orphenadrine syrup were determined by derivative spectroscopy. In each case spectral interference from formulation excipients was abolished. The accuracy, precision and specificity of each method has been established.

Analgesics, Opioid↗
PubMed1985

The stability of sodium nitroprusside infusion during administration by motorized syringe-pump.

This study examined the stability of concentrated sodium nitroprusside infusions during administration by a motorized syringe-pump system. Sodium nitroprusside and the free-cyanide degradation product were determined in infusion samples collected over periods of up to 24 h. Measures which were taken to protect the delivery system from light, ensured satisfactory stability of the infusion for at least 12 h from the time of preparation.

Cyanides↗