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The Pharmaceutical Journal Vol 265 No 7114 September 16, 2000
Pharmacy Practice Research
Papers presented at the British Pharmaceutical Conference, Birmingham, September 10 to 13, 2000 pR69

The stability of diamorphine and glycopyrrolate in PCA syringes

By J. Smith*, C. Hirsch, J. Marriott, K.Wilson and S. Nash

Introduction Diamorphine and glycopyrrolate mixtures are frequently administered by subcutaneous infusion to patients with terminal disease in order to alleviate both pain and excessive secretions.1 However, little is known about the chemical stability of these agents when mixed.
The present study was designed to examine the chemical stability of glycopyrrolate and diamorphine mixtures contained in patient controlled analgesia (PCA) syringes.

Method HPLC assays were based upon the United States Pharmacopeia XXIV method for glycopyrrolate injection and were performed using a Hewlett-Packard HP1100 instrument with autosampler, a variable wavelength detector (G1314A) and a 4.6x250mm Lichrosorb RP Select B column. Detection wavelength was set at 232nm and column oven temperature at 40C.
The compositions of test solutions were selected to mimic the dose forms currently administered in clinical practice over a 24-hour period1 (0.6mg glycopyrrolate and >15mg diamorphine). Three test solutions were prepared; all contained 0.6mg glycopyrrolate in 8ml combined with 5mg, 90mg or 200mg of diamorphine in a plastic syringe (Beckson & Dickson). Syringes were sealed with a blind hub (Braun) and stored in the dark at 32C prior to assay with three repeats at 0, 2 and 7 days.
Assays were found to be linear (diamorphine r=0.9998, glycopyrrolate r=0.9994) and reproducible within day (diamorphine %RSD=1.62, glycopyrrolate %RSD=1.91) and day-to-day (diamorphine %RSD=0.44, glycopyrrolate %RSD=2.47).

Focal points

  • Overall theme: Investigation of the chemical stability of diamorphine and glycopyrrolate in PCA syringes
  • Rationale: Diamorphine and glycopyrrolate mixtures are often administered by subcutaneous infusion in palliative care despite little being known of the chemical stability of these mixtures
  • Study design: HPLC analysis with repeats
  • Outcomes: Mixtures of diamorphine and glycopyrrolate used in clinical practice are likely to be chemically stable for the usual periods of administration

Results In the mixture containing 200mg diamorphine, concentrations of glycopyrrolate were reduced by 2.4 per cent (to 0.654±0.005 mg/mL) and 6.0 per cent (to 0.630±0.0003 mg/mL) at 2 and 7 days, respectively, whereas diamorphine concentrations were reduced by 3.5 per cent (to 187.3±1.0 mg/mL) and 9.3 per cent (to 176.1±0.6 mg/mL), respectively, at these times.
In the mixture containing 90mg diamorphine, concentrations of glycopyrrolate were reduced by 1.0 per cent (to 0.605±0.002 mg/mL) and 0.7 per cent (to 0.615±0.002 mg/mL) at 2 and 7 days, respectively, whereas diamorphine concentrations were reduced by 3.5 per cent (to 86.3±0.7 mg/mL) and 10.7 per cent (to 79.9±0.6 mg/mL), respectively, at these times.
In the mixture containing 5mg diamorphine, concentrations of glycopyrrolate were reduced by 4.4 per cent (to 0.591±0.001 mg/mL) and 0.5 per cent (to 0.615±0.006 mg/mL) at 2 and 7 days, respectively, whereas diamorphine concentrations were reduced by 12.9 per cent (to 4.19±0.02 mg/mL) and 15.2 per cent (to 4.08±1.08 mg/mL), respectively, at these times.
No significant consistent changes in sample pH were observed over the storage period.

Discussion The present study indicates that at the concentrations currently used in clinical practice, mixtures of diamorphine and glycopyrrolate would be chemically stable in PCA syringes for two days according to a nominal 10 per cent end of shelf life limit. Our study also showed that after seven days, there was some evidence of degradation of diamorphine. Further studies are necessary to define the total viable storage periods for these solutions but our results suggest that freshly prepared solutions would undergo minimal chemical degradation during the normal 24-hour administration period.

Pharmacy practice group, school of pharmacy, Aston university, Birmingham B4 7ET; *pharmacy department, Queen's hospital, Burton on Trent DE13 0RB

References

1. British National Formulary (No 38). London: British Medical Association and Royal Pharmaceutical Society; 1999.