Removing Polyethylene Glycol from Methylprednisolne Removing Polyethylene Glycol from Methylprednisolne Makes Suspension Safer for Intrathecal Use Makes Suspension Safer for Intrathecal Use

Kenneth D. Candido, MD, N. Nick Knezevic, MD, PhD, Jessen Mukalel, MD, Ivana Knezevic, MD*

Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657 USA *Department of Physiology and Biophysics, University of Illinois, Chicago, IL 60612 USA

Conclusions

References

Introduction

ResultsMethodsAbstract

• Intrathecal methylprednisolone (ITMP) is an effective treatment for postherpetic neuralgia.1-4

• Widespread use of ITMP is limited by the presence of polyethylene glycol (PEG) as a preservative in the commercial formulation.• Complications of high-concentration PEG in the intrathecal space include meningitis, transverse myelitis, cauda equina syndrome, lumbar radiculitis, intractable headache, and urinary retention.5-7 • In this study, we are proposing a method to reduce the concentration of PEG in the methylprednisolone acetate (MPA) suspension by inverting a vial before sterilely aspirating the vial contents into a syringe for subsequent injection.

• The single dose vials containing 80 mg of MPA suspension (Depo-Medrol®, Pharmacia & Upjohn Company, Kalamzoo, MI) (Figure 1A) were inverted to promote partition of the PEG away from the steroid component (Figure 1B).

• After achieving two phases, we carefully extracted and aspirated only the steroid component.

• While keeping the vial inverted, a 3mL syringe with an 18 Gauge blunt tipped-needle was gently inserted into the vial, aspirating the bottom part containing methylprednisolone, until only the upper part containing PEG remained in the vial (Figure 1C).

• We kept vials inverted for different time points (30, 60, 120, 240, 360, and 480 minutes), and measured the concentration of PEG by using liquid chromatography and mass spectrometry (Mass Spectrometry Lab, Research Resource Center, University of Illinois, Chicago).

• Liquid chromatography was performed by using an Agilent 1100 Series binary pump, vacuum degasser, auto sampler, and thermostated column compartment system.

• The Agilent 1100 Series MSD Single Quadrapole LC/MS mass spectrometer was used to detect the PEG.

• The results of the analysis were processed by Agilent Chem Station software.

• The pH of samples was measured by using the pH-meter for small samples (Thermo Fisher Scientific, Waltham, MA).

• The average concentration of PEG in the sample after 30 minutes was 8.02±1.51 mg/ml (Figure 2). • Since the concentration of PEG in the commercial vial is 28 mg/ml, about 70% of PEG was removed by inverting the vial. • By inverting the vial longer (120 and 240 minutes), the average concentration of PEG was 4.30±1.07 mg/ml and 4.13±0.77 mg/ml respectively. • We removed about 85% of PEG by keeping the vial inverted from two to four hours. • Inverting the vial longer (360 and 480 minutes) did not reduce the concentration of PEG further.• The pH of solution was not changed by removing PEG and was between 6.91 and 6.97.

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• A preservative-free, commercial formulation of methylprednisolone does not exist. • By keeping a vial of MPA suspension inverted for more than two hours, we greatly reduced the concentration of PEG in the suspension.• We believe that decreasing in PEG concentration by using our method will reduce the risk of complications, and should be considered in patients with postherpetic neuralgia refractory to other treatments.

1. Alper BS, et al. J Fam Pract 2002;51:121-8.2. Kikuchi A, et al. Reg Anesth Pain Med 1999;24:287-93.3. Kotani N, et al. N Engl J Med 2000;343:1514-9.4. Candido KD, et al. Int Anesthesiol Clin 2010; In Press5. Nelson DA. Arch Neurol 1988;45:804-6.6. Nelson DA, et al. N Engl J Med 2001;344:1019.7. Nelson DA. Spine (Phila Pa 1976) 1993;18:278-86.

Figure 1. Removing polyethylene glycol (PEG) from methylprednisolone suspesnsion. A. A vial of MPA injectable suspension (Depo-Medrol®, Pharmacia & Upjohn Company, Kalamazoo, MI), B. The vial inverted for different time points before aspiration, with 2 different phases; an aqueous phase containing PEG is circled. C. The vial after aspiration. The aqueous phase containing PEG left after aspiration is circled.

*From Candido, KD, et al. Management of Postherpatic Neuralgia with Intrathecal Methylprednisolone. Int Anesthesiol Clin 2010; In Press

Figure 2. The average concentration of PEG after inverting vials for certain time (6 vials per time point)

We are proposing a method to reduce the concentration of PEG in the methylprednisolone acetate (MPA) suspension by inverting a vial before sterilely aspirating the vial contents into a syringe for subsequent injection.We kept vials inverted for different time points (30 - 480 min), and measured the concentration of PEG by using liquid chromatography and mass spectrometry.Our results showed that by keeping a vial of MPA suspension inverted for more than two hours, we removed about 85% of PEG. We believe that this method should be considered to reduce the risk of complications, and make MPA suspension safer for intrathecal use.

p=0.008