Quality of intrathecal baclofen from different sources

Abstract

Objective: To compare the quality of intrathecal baclofen obtained from a national compounding pharmacy (AnazaoHealth) with the manufactured product (Lioresal) with regard to accuracy and precision of baclofen concentration, and the content of the baclofen degradation product, 4-(4-chlorophenyl)-2-pyrrolidinone (PYR).

Design: Samples of baclofen used for refilling intrathecal pumps were placed in 1.2-mL silicone gasket-sealed cryogenic vials and stored at or lower than -25°C. Each sample was a different lot number (Lioresal) or prescription number (AnazaoHealth). The laboratory was blinded to the source of the solutions. Coupled with electrospray ionization-mass spectrometry analyte confirmation, quantitation of baclofen and PYR in each sample was performed in duplicate by using high-performance liquid chromatography with ultraviolet detection via a photodiode array detector.

Setting: Outpatient clinic.

Participants: Patients with intrathecal baclofen pumps.

Main outcome measures: Accuracy and precision of baclofen concentration, and concentration of PYR.

Results: The difference of mean concentrations from expected concentrations of 500 and 2000 μg/mL were significantly greater for samples from AnazaoHealth compared with Lioresal. Values are shown as mean (± standard error), with n the number samples, for AnazaoHealth compared with Lioresal: (537.1 ± 6.7 μg/mL [n = 8] versus 515.6 ± 0.82 μg/mL [n = 5]; P = .034, respectively) and (2211.4 ± 21.6 μg/mL [n = 12] versus 2055.3 ± 8.7 μg/mL [n = 4]; P = .004, respectively). AnazaoHealth samples with expected concentration of 4000 μg/mL were 3987.7 ± 79.9 μg/mL, n = 7. All 9 Lioresal samples were within 5% of the expected concentration. Of 27 AnazaoHealth samples, 22 were more than 5%, and 8 were more than 10% different from the expected concentration. No PYR was detected in any sample from AnazaoHealth. All samples of Lioresal contained PYR, but all solutions contained less PYR than 1% of the baclofen concentration.

Conclusions: Lioresal was more accurate in concentration and more precise among batches than compounded intrathecal baclofen but had higher levels of PYR.