Determination of the microbiological stability of intrathecal chemotherapy

Introduction

Treatments of haemotological malignancies often require intrathecal administration of chemotherapy.
We tried to assess the microbological stability of our preparations, during a 96-hour period, to avoid reconstitution by the on-duty resident.

Materials and methods

Three molecules were tested: methotrexate, cytarabine and methylprednisolone.

Method, micro-organisms and experimental conditions (culture media, incubation temperature) were those described by the European Pharmacopea (8^th edition, chapter 2.6.1).

Four tests were carried out: three to assess the experimental conditions (media sterility test, media fertility test; method applicability test) and one to determinate the microbiological stability (products sterility test).

The tests were carried out in triplica to ensure reproducibility.

Results

For the media, sterility and fertility tests were conclusive.

For the method applicability test:

• No inhibition of bacterial growth was observed for cytarabine and methotrexate
• No micro-organism growth was observed with methylprednisolone. This test became conclusive by using blood culture media.

The fertility test at day 0 and day 4 did not show any micro-organism growth.

Discussion and conclusion

The three tests assessing the experimental conditions showed that they were good. That allowed us to realise the product sterility test with optimal conditions.

Absence of micro-organism growth during the product sterility test proved that our preparations remain sterile during a 96-hour period.

We will be able to anticipate the preparation of intrathecal chemotherapy and so, improve the security of those high-risk products, in particular during on-duty time.