Any analytical method must strike a balance between its intrinsic scientific potential its capacity for robustness and reliability, particularly in regulated industries.
In the case of HPLC, this balancing act is part of an initiative by the U.S. Pharmacopeia (USP), which is modernizing its pharmaceutical monographs.
A monograph is “the book” on a drug product. Besides specifying the active ingredient’s chemical composition and the product’s ingredients, packaging, storage, and labeling, a monograph describes the analytical methods required to ensure strength, quality, and purity.
“These tests need to be very selective, sensitive, and precise,” says Petra Lewitz, product manager for analytical chromatography at EMD Millipore. “In that context, HPLC is preeminent, but it is not the only method.”
In many USP monographs, the specified analytical methods are completely out of date. The USP is therefore recruiting industrial collaborators to provide sensitive, robust, current methods that improve overall understanding about pharmaceuticals and enable labs to operate more efficiently.
For example, many monographs rely on C18 columns, but as Lewitz notes many pharmaceuticals are polar or hydrophilic: “This stationary phase lacks selectivity and sensitivity for many pharmaceutical compounds unless ion-pairing agents are employed. But then, they become unsuitable for mass spectrometric analysis.”
In this case switching to a more selective column, such as a hydrophilic interaction liquid chromatography (HILIC) column, or a slightly smaller particle size, might be sufficient for method modernization. “You don’t have to change the instrument,” Lewitz adds.
Interestingly, Lewitz does not categorically endorse such modern alternatives as UHPLC or core shell columns. Column clogging, she observes, is too likely using these technologies, especially with complex matrices such as formulated drugs.
For that reason, Lewitz favors monolithic columns, which provide the backpressure advantages of core shell (and HPLC) but will stand up to harsh, complex samples. “It’s important to find the best compromise between speed, resolution, and robustness.”