troubleshoot-separation
О программе
Этот навык Claude систематически диагностирует и решает проблемы хроматографического разделения в ГХ и ВЭЖХ. Он помогает документировать симптомы, выявлять коренные причины аномалий формы пиков и удерживания, а также оценивать матричные эффекты. Разработчикам следует использовать его для внедрения целевых исправлений с помощью структурированного подхода, изменяя по одной переменной за раз.
Быстрая установка
Claude Code
Рекомендуетсяnpx skills add pjt222/agent-almanac -a claude-code/plugin add https://github.com/pjt222/agent-almanacgit clone https://github.com/pjt222/agent-almanac.git ~/.claude/skills/troubleshoot-separationСкопируйте и вставьте эту команду в Claude Code для установки этого навыка
Документация
Troubleshoot Chromatographic Separation
GC/HPLC sep diagnosis → symptom doc → peak shape diag → retention anomaly → matrix effects → verified fix via one-var-at-time.
Use When
- Peaks tail|front|split|broaden
- Retention shifted|irreproducible
- Resolution between critical pairs degraded
- Baseline drift|ghost peaks|negative peaks
- Sensitivity drop|S/N worse
- Working method now fails sys suitability
In
Required
- Problem chromatogram: Current data → issue
- Reference chromatogram: Recent good, same method → compare
- Method conditions: Column, mobile phase|carrier gas, temp|gradient, detector, flow
- System log: Recent maint, col changes, mobile phase prep, instrument events
Optional
- Blank chromatogram: Most recent blank|solvent inj
- Sys suitability trends: Historical tailing, resolution, plates, RT
- Col history: # injections, sample types, age
- Instrument maint log: Pump seal, lamp hrs, detector service
Do
Step 1: Doc Problem
- Symptom precise: which peaks, how differ from ref
- When started: gradual|sudden
- All peaks or specific?
- Standards|samples|both?
- Current sys suitability vs historical
- Photo|export problem chromatogram side-by-side w/ ref
Got: Problem statement w/ timeline, scope (all|specific peaks, std|sample), ref comparison.
If err: No ref → inject fresh standard prep under documented method → establish current baseline before troubleshoot.
Step 2: Diag Peak Shape
| Symptom | Possible Causes | Solutions |
|---|---|---|
| Tailing (T > 1.5) | Secondary interactions (silanol activity), dead volume in fittings, contaminated column frit, overloaded active sites | Add amine modifier (HPLC), deactivate liner (GC), replace frit, trim column inlet, reduce injection mass |
| Fronting (T < 0.8) | Column overload (mass or volume), mismatch between sample solvent and mobile phase strength | Reduce injection volume or concentration, dilute in weaker solvent, use larger-bore column |
| Split / double peaks | Partially blocked frit, void at column head, two polymorphic forms, isomeric interconversion | Replace frit, repack column head, verify sample stability, adjust pH to lock one form |
| Broad peaks (all) | Extra-column band broadening, wrong tubing ID, large detector cell, old column, low plate count | Minimize post-column tubing length and ID, check connections, replace column |
| Broad peaks (early eluters) | Poor focusing at column head, injection solvent too strong (HPLC), cold on-column (GC) | Use weaker injection solvent, reduce injection volume, increase initial oven temp |
| Broad peaks (late eluters) | On-column diffusion, temperature too low (GC), insufficient gradient steepness (HPLC) | Increase final oven temperature, steepen gradient, add organic wash |
| Negative peaks | Sample solvent refractive index/absorbance differs from mobile phase, vacancy peaks (IEX) | Match sample solvent to mobile phase, use different detection wavelength |
| Ghost peaks | Carryover from previous injection, contaminated mobile phase, column bleed, septum bleed (GC) | Run blank to confirm, clean or replace injection system, filter/degas mobile phase, replace septum |
| Baseline drift (upward) | Column bleed (GC at high temp), gradient elution baseline shift (HPLC), lamp instability (UV) | Reduce max temp, use low-bleed column (GC), run blank gradient to characterize (HPLC), replace lamp |
| Baseline noise (high-frequency) | Electrical interference, pump pulsation, air bubbles in detector, contaminated detector | Ground instrument, replace pump seals, degas mobile phase, clean detector cell |
- Match symptom(s) → table
- Narrow causes: all peaks|specific, sudden|gradual
- Prioritize → sys history (recent changes, col age, maint)
Got: 1-2 most-likely causes from sym-cause map, prioritized by history.
If err: No table match or multi-symptom → compound problem (col degradation + leak). Address obvious first → re-eval.
Step 3: Diag Retention
| Symptom | Possible Causes | Solutions |
|---|---|---|
| All peaks shifted earlier | Increased flow rate, higher column temperature, stronger mobile phase, column void | Check flow rate setting and actual delivery, verify temperature, remake mobile phase, inspect column |
| All peaks shifted later | Decreased flow rate, lower column temperature, weaker mobile phase, partially blocked tubing | Check for leaks (pressure drop), verify temperature, remake mobile phase, check inline filter |
| Retention time drift (gradual) | Column degradation, mobile phase evaporation (open reservoir), temperature fluctuation | Replace column, seal reservoir, stabilize oven, use column thermostat |
| Retention time irreproducible | Leak at fitting, check valve malfunction, autosampler timing error, inadequate re-equilibration | Pressure-test fittings, replace check valves, verify autosampler, increase equilibration volume |
| Lost retention (k' near 0) | Phase collapse (RP at high aqueous), column dewetting, wrong mobile phase, reversed connections | Use polar-embedded or AQ-type column, re-wet column with organic, verify mobile phase, check plumbing |
| Co-elution (previously resolved) | Column selectivity lost (bonded phase stripped), mobile phase composition changed, temperature changed | Replace column, verify mobile phase preparation, check temperature setpoint vs. actual |
- Shifts uniform (all) or selective (specific)?
- Uniform → systematic (flow, temp, mobile phase)
- Selective → col chemistry|specific analyte
- Check pressure trace: sudden change → leaks|blockage
- Re-inject ref std → confirm sys vs sample
Got: Retention root cause categorized: systematic (instrument/MP) or col-related.
If err: Re-inject std on new col resolves → orig col = problem. Persists on new col → upstream (MP, instrument, method).
Step 4: Matrix Effects
- Std vs sample chromatogram:
- Extra peaks in sample absent from std?
- Baseline elevated|noisy in retention windows?
- Analyte peaks differ in sample vs std (broader, more tailing)?
- LC-MS → ion suppression/enhancement:
- Post-col infusion: infuse analyte continuous while inject blank matrix → dips = suppression regions
- Analyte RT coincides w/ suppression → shift elution
- Col contamination:
- Solvent blanks after sample seq → persistent peaks = col contamination
- Flush col w/ strong solvent (100% organic for RP, or per mfr)
- Sample prep:
- Dirty injector (autosampler needle, GC liner) → replace|clean
- Insufficient cleanup → add filter, SPE, protein precipitation
- GC: non-volatile residue in inlet liner → causes tailing + ghost over time
Got: Matrix effects characterized (interferents, ion suppression zones for LC-MS, col contamination) w/ actions.
If err: Can't characterize → matrix-matched cal curve vs solvent cal curve. Slope diff > 15% → significant matrix effects → method mod.
Step 5: Fix + Verify
- One var at a time. Doc what + why.
- Per change → re-inject sys suitability std vs ref
- Sequence (least → most disruptive):
- Fresh mobile phase | carrier gas tank
- Replace consumables (septum, liner, frit, inline filter, lamp)
- Tighten|replace fittings + tubing
- Flush|regen col
- Adjust method (temp, flow, gradient, pH)
- Replace col
- Service instrument (pump seals, check valves, detector)
- Fix found → full sys suitability test (n >= 5 injections)
- Compare all params (RT, area, resolution, tailing, plates) vs spec
- Doc root cause, action, verify in instrument|col logbook
- Recurs → preventive maint schedule
Got: Problem resolved, sys suitability params restored to spec. Root cause + action + verify documented.
If err: All single-var changes fail → multi simultaneous failures. Replace all consumables + col together → verify w/ fresh std → rebuild from new baseline. Persists after total replacement → escalate to instrument service.
Check
- Problem documented w/ symptom, timeline, scope
- Root cause via sym-cause maps
- One var at a time
- Fix verified by sys suitability (n >= 5 replicate inj)
- All sys suitability params restored to spec
- Root cause + action in logbook
- Preventive measure ID'd
Traps
- Multi vars at once: Can't ID root cause. One change → test → decide.
- Col first: Expensive, masks real problem (leak, wrong MP, contaminated inlet). Exhaust simpler first.
- Ignore logbook: Many problems → recent maint, MP batch, col swap. Check what changed.
- Blame sample w/o evidence: Run ref std first. Std also shows problem → sys, not sample.
- Incompatible solvents: Never flush RP w/ pure water (phase collapse) or silica HILIC w/ pure aqueous (irreversible). Per mfr protocol.
- No documentation: Failed attempts valuable. Record every change + outcome → avoid repeat + build knowledge.
→
interpret-chromatogram— understanding chromatographic data revealing sep problemsdevelop-gc-method— GC method dev, relevant when troubleshooting requires redesigndevelop-hplc-method— HPLC method dev, relevant when troubleshooting requires redesignvalidate-analytical-method— re-validation may need after significant method changes
GitHub репозиторий
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