Senior/Principal Scientist, Analytical & Bioanalytical Chemistry

Switch Therapeutics; South San Francisco (CA); On-site; USD 150,000 - 180,000; Full time

Benefits offered by this job

Equity in the Company

Discretionary annual bonus

Healthcare benefits

Paid time off

Job summary

Switch Therapeutics in South San Francisco is seeking a Senior/Principal Scientist to lead bioanalytical characterization of oligonucleotide therapeutics, integrating LC–MS/MS and LC–HRMS with PK/PD interpretation. This hands-on role guides method strategy and mentors junior scientists while collaborating across discovery and biology teams.

The position is full-time onsite with a competitive base salary and a compensation package including equity, a discretionary annual bonus, and comprehensive

Qualifications

• Ph.D. in Analytical Chemistry, Biochemistry, Chemistry, or a related field; with bioanalytical experience (or M.S. with hands-on experience).
• Strong hands-on expertise developing LC–MS/MS and HRMS methods for quantitative bioanalysis.
• Experience with bioanalysis of oligonucleotides (ASOs, siRNA) or applying MS to novel analytes.
• Experience extracting and quantifying analytes from plasma and tissue matrices.
• Ability to mentor in a collaborative environment.
• Excellent problem-solving and communication skills.

Responsibilities

• Develop and optimize LC–MS/MS and LC–HRMS methods for oligonucleotides and metabolites across biological matrices.
• Quantify drug exposure and link analytical readouts to PK/PD understanding.
• Provide technical mentorship and shaping method strategy for the oligonucleotide portfolio.
• Collaborate with Discovery Chemistry and biology teams to inform study design.
• Maintain rigorous, well-documented data; write method summaries and study reports.

Skills

LC–MS/MS

HRMS

Bioanalysis

Mentorship

Mass spectrometry

Education

PhD in Analytical Chemistry

Tools

Orbitrap

LC–HRMS

Liquid–Liquid Extraction

Job description

We are seeking a Senior/Principal Scientist to lead the bioanalytical/analytical characterization of our oligonucleotide therapeutics. The role blends strong mass spectrometry capability with a broader bioanalytical and pharmacokinetic remit: you will develop and apply LC–MS/MS and LC–HRMS methods to quantify drug exposure and characterize stability and metabolism and connect those analytical results to pharmacokinetic and pharmacodynamic understanding.

You will work across the analytical workflow — from analyzing and extracting oligonucleotides out of plasma and complex tissues, through method development and data interpretation, to translating findings for project teams. It is a hands-on role that also carries technical influence: guiding method strategy and helping more junior scientists grow.

This role will require full-time onsite work at our research facilities in South San Francisco.

The pay range for this position at commencement of employment is expected to be between $150,000–$180,000 per year depending on experience. Base pay offered may vary depending on other factors, including job-related knowledge, skills, and experience. The total compensation package for this position may also include equity in the Company, a discretionary annual bonus, and a full range of healthcare and other benefits, including 401(k) eligibility and paid time off (including vacation, sick time, and parental leave). Details of participation in these benefit plans will be provided if a candidate receives an offer of employment.

If hired, the employee will be in an “at-will position” and the Company reserves the right to modify base salary (as well as any other discretionary payment or compensation program) at any time, including for reasons related to individual performance, Company or individual department/team performance, and market factors.

• Bioanalytical Method Development:Develop and optimize LC–MS/MS and LC–HRMS methods for the quantitative and structural analysis of oligonucleotides and their metabolites across biological matrices, applying ion-pairing and HILIC chromatography as appropriate.
• Mass Spectrometry:Apply triple-quadrupole and high-resolution (Orbitrap) mass spectrometry for quantification, accurate-mass confirmation, and metabolite identification; troubleshoot chromatographic and mass-spec performance to keep assays robust.
• Tissue Extraction & Sample Preparation:Design and troubleshoot extraction workflows to recover oligonucleotides from plasma and challenging tissues (e.g., liver, kidney, muscle, CNS), including homogenization, solid-phase, and liquid–liquid extraction that maximize recovery and minimize matrix effects.
• Technical Guidance:Help shape bioanalytical method strategy for the oligonucleotide portfolio and provide technical mentorship to junior scientists and associates, sharing best practices at the bench.
• Cross-Functional Collaboration:Partner with Discovery Chemistry, in-vitro and in-vivo teams to connect analytical readouts to biology and inform molecule and study design.
• Data Integrity & Communication:Maintain rigorous, well-documented, reproducible data; author method summaries and study reports and communicate findings clearly to inform decisions.

Required Qualifications

• Ph.D. in Analytical Chemistry, Biochemistry, Chemistry, or a related field, with relevant bioanalytical experience (or M.S. with commensurate hands-on experience).
• Strong hands-on expertise developing and running LC–MS/MS and high-resolution mass spectrometry methods for quantitative bioanalysis.
• Experience with the bioanalysis of oligonucleotides (e.g., ASOs, siRNA), or a demonstrated ability to apply MS and bioanalytical expertise to novel analytes.
• Experience extracting and quantifying analytes from complex biological matrices, including plasma and tissue homogenates.
• Ability to provide technical guidance and mentorship in a collaborative, cross-functional environment.
• Excellent problem-solving, data-integrity, and written/verbal communication skills.

Preferred Qualifications

• Experience with ion-pairing reversed-phase and HILIC chromatography for oligonucleotides.
• Familiarity with chemically modified oligonucleotides and conjugation chemistries and their disposition implications.
• Exposure to orthogonal readouts (hybridization ELISA, qPCR, ddPCR) that complement LC–MS quantification.
• Experience supporting discovery, toxicology, and/or biodistribution studies, and/or contributing to regulatory submissions.

About Switch

Switch Therapeutics is an emerging biotechnology company that is developing RNAi therapies stemming from transformative technologies invented at Caltech, City of Hope, and Harvard Medical School.

Switch’s conditionally activated siRNA (CASi) platform integrates RNA nanotechnology with RNA medicinal chemistry to create siRNA prodrugs that can activate or suppress their own drug activities based on the presence or absence of specific RNA markers in mammalian cells. This gives CASi-based drugs the ability to target specific cells responsible for disease while sparing non-target cells from drug activity.

Since its founding in Q3 2020, Switch has made significant progress in optimizing its technology for therapeutic applications and has generated highly compellingin vivovalidation data demonstrating distribution, potency, and duration of effect that support development for important disease indications.